bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular docking and molecular dynamics simulation of wheat gluten‐derived antioxidant peptides acting through the Keap1–Nrf2 pathway
Authors: Liu Wenying , Liu Rui , Qin Qingyu , Wang Hualei , Zhang Xinxue , Meng Ganlu
Published: June 2024

BACKGROUND

In our previous study, we successfully identified five peptides from wheat gluten: Ala‐Pro‐Ser‐Tyr (APSY), Leu‐Tyr (LY), Pro‐Tyr (PY), Arg‐Gly‐Gly‐Tyr (RGGY) and Tyr‐Gln (YQ). Molecular docking and molecular dynamics simulation methods were employed to investigate the interaction between these antioxidant peptides and the Kelch‐like ECH‐associated protein 1 (Keap1 protein), revealing the molecular mechanism of their non‐competitive binding. In addition, the total antioxidant capacity of the five peptides was determined using the 2,2′‐azinobis(3‐ethylbenzothiazoline‐6‐sulfonic acid) diammonium salt (ABTS) method.

RESULTS

The affinities of APSY, LY, PY, RGGY and YQ were −8.9, −8.3, −8.5, −9.1 and − 7.9 kcal mol−1, respectively. The five peptides effectively bound to Keap1 protein through hydrogen, π‐σ, π‐alkyl and alkyl interactions. Significant roles were observed for the P1 pocket residue ARG‐415 and the P3 pocket residue ALA‐556 in the interactions of the Keap1–peptide complexes. Molecular dynamics simulations further elucidated the dynamic process of peptide binding to the Keap1 protein. All five peptides formed stable complexes with Keap1 protein, with van der Waals forces playing crucial roles in these complex systems, indicative of the peptides' strong binding ability to Keap1 protein. The van der Waals forces were −178.74, −123.11, −134.36, −132.59, and −121.44 kJ mol−1 for the Keap1–APSY, Keap1–LY, Keap1–PY, Keap1–RGGY and Keap1–YQ complexes, respectively. These peptides exhibited excellent antioxidant effects. Among them, the YQ peptide exhibited the highest total antioxidant capacity, with an activity value of 1.18 ± 0.06 mmol Trolox equivalent (TE) L−1 at a concentration of 0.10 mg mL−1. The RGGY, PY, LY and APSY peptides followed in descending order, with activity values of 0.91 ± 0.05, 0.72 ± 0.06, 0.62 ± 0.04 and 0.60 ± 0.05 mmol TE L−1, respectively.

CONCLUSION

These results unveiled the molecular mechanism by which the five antioxidant peptides act on active pockets through the Keap1–Nrf2 signaling pathway, providing a theoretical basis for the development of antioxidants. © 2024 Society of Chemical Industry.
Reliability of artificial intelligence chatbot responses to frequently asked questions in breast surgical oncology
Authors: Roldan‐Vasquez Estefania , Mitri Samir , Bhasin Shreya , Bharani Tina , Capasso Kathryn , Haslinger Michelle , Sharma Ranjna , James Ted A.
Published: June 2024

Introduction

Artificial intelligence (AI)‐driven chatbots, capable of simulating human‐like conversations, are becoming more prevalent in healthcare. While this technology offers potential benefits in patient engagement and information accessibility, it raises concerns about potential misuse, misinformation, inaccuracies, and ethical challenges.

Methods

This study evaluated a publicly available AI chatbot, ChatGPT, in its responses to nine questions related to breast cancer surgery selected from the American Society of Breast Surgeons' frequently asked questions (FAQ) patient education website. Four breast surgical oncologists assessed the responses for accuracy and reliability using a five‐point Likert scale and the Patient Education Materials Assessment (PEMAT) Tool.

Results

The average reliability score for ChatGPT in answering breast cancer surgery questions was 3.98 out of 5.00. Surgeons unanimously found the responses understandable and actionable per the PEMAT criteria. The consensus found ChatGPT's overall performance was appropriate, with minor or no inaccuracies.

Conclusion

ChatGPT demonstrates good reliability in responding to breast cancer surgery queries, with minor, nonharmful inaccuracies. Its answers are accurate, clear, and easy to comprehend. Notably, ChatGPT acknowledged its informational role and did not attempt to replace medical advice or discourage users from seeking input from a healthcare professional.
Endoscopic‐Assisted Cochlear Implantation via a “Microfacial Recess”
Authors: Din Taseer F. , Abdulkader Faisal , Chang Kay W.
Published: June 2024

Syndromic patients can have severely anomalous anatomy significantly challenging conventional cochlear implant (CI) surgery. This case report describes a 20‐year‐old with brachio‐oto‐renal syndrome with a severely anomalous facial nerve completely covering the round window and preventing a traditional posterior tympanotomy CI. This is the first report to illustrate the performance of an endoscopic trans‐canal bony cochleostomy with insertion of the CI performed via a “microfacial recess.” We describe the performance of an endoscopic trans‐canal bony cochleostomy and a modification of the conventional wide posterior tympanotomy usually performed into a 1 mm “microfacial recess,” which allowed a full insertion to take place. Laryngoscope, 134:4806–4809, 2024
Decadal warming has intensified Microcystis‐dominated cyanobacterial blooms in Lake Erie
Authors: Gobler Christopher J. , Di Cecco Grace J. , Doherty Owen M. , Kramer Benjamin J.
Published: June 2024

Cyanobacterial harmful algal blooms (CHABs) are increasingly common in freshwater ecosystems and are often associated with climate change. Here, we used two independent high‐resolution surface temperature records (1995–2022) and temperature‐dependent growth rates of Microcystis to evaluate changes in these CHABs in Lake Erie. The potential mean seasonal growth rate of Microcystis and the duration of the Microcystis bloom season have both significantly increased within the western basin of Lake Erie since 1995. Trends were strongest in the far western region of Lake Erie including Maumee Bay which receives the largest point source of nutrients in the Lake and where the Microcystis bloom season has expanded by up to 1 month. In contrast, warming trends in bloom‐free portions of central and eastern Lake Erie have been more muted. We conclude that increasing water temperature is an important factor facilitating the intensification of these, and likely other, CHABs, and is thus promoting an expanding public health threat.
Appendicular lean mass index and motor function in ambulatory patients with Duchenne muscular dystrophy
Authors: Kiefer Michael , Townsend Elise , Goncalves Celina , Shellenbarger K. Courtney , Gochyyev Perman , Wong Brenda L.
Published: June 2024

Introduction/Aims

Appendicular lean mass index (ALMI) has been linked to motor function in patients with Duchenne muscular dystrophy (DMD). However, quantification of the relationship between ALMI and disease‐specific clinical outcome assessment trajectories is needed. The purpose of this study was to determine associations between dual‐energy x‐ray absorptiometry (DXA) derived estimates of ALMI and motor function in ambulatory patients with DMD.

Methods

A retrospective analysis of longitudinal clinical visit data from 137 glucocorticoid‐treated patients with DMD collected via structured motor assessment protocol evaluated associations between ALMI and motor function indexed by the North Star Ambulatory Assessment (NSAA) and 10 Meter Walk/run Test (10MWT). Body composition was assessed using DXA. ALMI was calculated by dividing arm and leg lean mass by height in m2; fat mass index (FMI) was calculated by dividing whole body fat mass by height in m2. Linear mixed‐effects models were used to estimate associations between ALMI and motor function, controlling for age and FMI.

Results

The full prediction model (age, age,2 ALMI, and FMI) explained 57% of the variance in NSAA scores and 63% of the variance in 10MWT speed. A 1 kg/m2 higher ALMI value predicted a 5.4‐point higher NSAA score (p < .001) and 0.45 m/s faster 10MWT speed (p < .001). A 1 kg/m2 higher FMI value predicted a 1.5‐point lower NSAA score (p < .001) and 0.14 meters/second slower 10MWT speed (p < .001).

Discussion

DXA‐derived estimates of ALMI and FMI are associated with motor function in DMD and may explain variation in DMD disease progression.
A cops and robber game and the meeting time of synchronous directed walks
Authors: Ben‐Ameur Walid , Maddaloni Alessandro
Published: June 2024

In a previous work, the authors showed that the maximum number of infinitely long synchronous directed walks that never meet is equal to the dimension of the no‐meet matroid, namely the largest order of a collection of vertex‐disjoint cycles. Given , we want to compute the meeting time of walks: the first time step such that, given any set of
walks, at least two of them must meet no later than . We precisely prove that the meeting time is at most , where is the number of vertices. A connection is established with a cops and robber game on directed graphs with helicopter cops and an invisible slow robber. The meeting time of walks equals the capture time in this game, when at most
capture attempts are allowed. While this capture time can be computed in polynomial time, we show that it is NP‐hard to compute the minimum number of cops needed to catch the robber. More insights are also given on the number and its relation to pathwidth and other graph parameters. Finally we analyze these game measures on digraph tensor products.
Elastic constant ratio for fatigue evaluation on rubber isolators
Authors: Luo Robert Keqi
Published: June 2024

In this study, a new concept of the elastic constant ratio was introduced to derive an S‐N base function, which has removed the requirement of the shear modulus to be measured in previous work, allowing much wider applications in fatigue prediction with significant reduction in the costs involved in conducting experiments and acceleration of the design process in industries. In this approach, the damage parameter was the effective tensile stress verified for both positive and negative R ratios (the ratio between the minimum stress and the maximum stress). Existing work only provided a general description of the criterion without detailed explicit equations, which does not provide sufficient clarity to the reader and could lead to variable fatigue life predictions. Here, detailed equations are introduced on the calculation procedure to allow accurate results to be obtained for fatigue assessment. The applicability of the approach was validated using two industrial components, that is, the Metacone spring and the bush spring. The maximum values of the damage parameter corresponded to the same failure locations observed in the experiments. The suggested S‐N base function, correlated with different materials and failure cycles, could be applied in a fatigue design stage and failure analysis for rubber isolators.

Highlights

For the first time, an elastic constant ratio is introduced on different rubbers.

There is no additional test required for the material constants to save cost.

The approach is experimentally validated on two industrial isolators.

Monitoring stiffness in tests cannot determine the crack initiation accurately.
A qualitative study of strategies to improve occupational well‐being in physical medicine and rehabilitation physicians
Authors: Amano Alexis , Makowski Maryam S. , Trockel Mickey T. , Menon Nikitha K. , Wang Hanhan , Sliwa James , Weinstein Stuart , Kinney Carolyn , Paganoni Sabrina , Verduzco–Gutierrez Monica , Kennedy David J. , Knowlton Tiffany , Stautzenbach Thomas , Shanafelt Tait D.
Published: June 2024

Background

Physiatry is a specialty with high rates of burnout. Although organizational strategies to combat burnout are key, it is also important to understand strategies that individual physiatrists can use to address burnout.

Objective

To identify changes that resulted in improvement of occupational well‐being of physiatrists over a 6‐ to 9‐month period.

Design

We employed two quantitative surveys spaced 6 to 9 months apart to identify physiatrists who experienced meaningful improvement in occupational burnout and/or professional fulfillment between the two survey timepoints. These physiatrists were subsequently recruited to participate in a qualitative study using semi‐structured interviews to identify changes that respondents felt contributed to improvements in burnout and professional fulfillment.

Setting

Online surveys and interviews.

Participants

Physiatrists in the American Academy of Physical Medicine and Rehabilitation (AAPM&R) Membership Masterfile.

Main Outcome Measure

Burnout and professional fulfillment were assessed using the Stanford Professional Fulfillment Index.

Results

One hundred twelve physiatrists responded to the baseline and follow‐up surveys. Of these, 35 were eligible for interviews based on improvements in the Stanford Professional Fulfillment Index, and 23 (64%) agreed to participate. Themes from the qualitative interviews highlighted the importance of personal lifestyle choices, approaches to improve professional satisfaction, and strategies to foster work‐life harmony. Personal lifestyle strategies included investing in wellness and mental health. Efforts to improve professional satisfaction included decreasing work intensity, prioritizing meaningful aspects of work, and building relationships with colleagues. Fostering work‐life harmony also included making trade‐offs in both domains, setting boundaries at work, setting expectations at home, and overcoming personal challenges.

Conclusion

Our findings illustrate that, in addition to organizational strategies demonstrated to be effective, there are actions that individual physiatrists can take to recover from burnout and foster professional fulfillment.
A reactive flame retardant based on thiadiazole and phosphaphenanthrene for improving the flame retardant and smoke inhibition properties of epoxy resins
Authors: Duan Huajun , Liu Weipeng , Zhang Chenhao , Chen Yuan , Li Ya , Gao Yuan , Zhang Juan , Kang Jin
Published: June 2024

It is difficult to effectively manage the emission of harmful smoke from flame‐retardant modified epoxy resins (EP). In order to solve this difficulty, a highly efficient flame‐resistant PAD containing phosphorus, nitrogen, and sulfur was synthesized using a simply one‐pot method employing 9,10‐dihydro‐9‐oxa‐10‐phosphaphenanthrene‐10‐oxide (DOPO), 2‐amino‐5‐mercapto‐1,3,4‐thiadiazole (AMT), and terephthalaldehyde for not only enhancing its flame retardant properties but also effectively suppressing the emission of fumes. Results have confirmed that the incorporation of 5 wt% flame retardant into the EP successfully passed the UL‐94 V‐0 rating, besides 24.2% reduction in the peak of smoke produce rate (PSPR), with outstanding fire‐resistant properties and effectively reduce smoke emissions. In addition, incorporating 7.5% of PAD into EP increased its flexural strength and modulus, from 78.4 and 2917.5 to 86.6 and 3162.9 MPa, respectively. Due to the abundance of reactive groups including sulfhydryl and secondary amine in PAD, as well as the nitrogen atoms presented in the thiadiazole and benzene rings of the phosphaphenanthrene structure, which could create hydrogen bonds with the matrix and participated in π‐π interactions, therefore, the mechanical properties of flame retardant epoxy resin (FREP) were greatly enhanced.
Innovations in the care of childhood interstitial lung disease associated with connective tissue disease and immune‐mediated disorders
Authors: Samad Aaida , Wobma Holly , Casey Alicia
Published: June 2024

Childhood interstitial lung disease (chILD) associated with connective tissue and immune mediated disorders is the second most common chILD diagnostic category. As knowledge of the molecular and genetic underpinnings of these rare disorders advances, the recognized clinical spectrum of associated pulmonary manifestations continues to expand. Pulmonary complications of these diseases, including ILD, confer increased risk for morbidity and mortality and contribute to increased complexity for providers tasked with managing the multiple organ systems that can be impacted in these systemic disorders. While pulmonologists play an important role in diagnosis and management of these conditions, thankfully they do not have to work alone. In collaboration with a multidisciplinary team of subspecialists, the pulmonary and other systemic manifestations of these conditions can be managed effectively together. The goal of this review is to familiarize the reader with the classic patterns of chILD and other pulmonary complications associated with primary immune‐mediated disorders (monogenic inborn errors of immunity) and acquired systemic autoimmune and autoinflammatory diseases. In addition, this review will highlight current, emerging, and innovative therapeutic strategies and will underscore the important role of multidisciplinary management to improving outcomes for these patients.
Joint modeling of monocyte HLA‐DR expression trajectories predicts 28‐day mortality in severe SARS‐CoV‐2 patients
Authors: Baudemont Gaelle , Tardivon Coralie , Monneret Guillaume , Cour Martin , Rimmelé Thomas , Garnier Lorna , Yonis Hodane , Richard Jean‐Christophe , Coudereau Remy , Gossez Morgane , Wallet Florent , Delignette Marie‐Charlotte , Dailler Frederic , Buisson Marielle , Lukaszewicz Anne‐Claire , Argaud Laurent , Laouenan Cédric , Bertrand Julie , Venet Fabienne ,   for the RICO study group
Published: June 2024

The recent SarsCov2 pandemic has disrupted healthcare system notably impacting intensive care units (ICU). In severe cases, the immune system is dysregulated, associating signs of hyperinflammation and immunosuppression. In the present work, we investigated, using a joint modeling approach, whether the trajectories of cellular immunological parameters were associated with survival of COVID‐19 ICU patients. This study is based on the REA‐IMMUNO‐COVID cohort including 538 COVID‐19 patients admitted to ICU between March 2020 and May 2022. Measurements of monocyte HLA‐DR expression (mHLA‐DR), counts of neutrophils, of total lymphocytes, and of CD4+ and CD8+ subsets were performed five times during the first month after ICU admission. Univariate joint models combining survival at day 28 (D28), hospital discharge and longitudinal analysis of those biomarkers’ kinetics with mixed‐effects models were performed prior to the building of a multivariate joint model. We showed that a higher mHLA‐DR value was associated with a lower risk of death. Predicted mHLA‐DR nadir cutoff value that maximized the Youden index was 5414 Ab/C and led to an AUC = 0.70 confidence interval (95%CI) = [0.65; 0.75] regarding association with D28 mortality while dynamic predictions using mHLA‐DR kinetics until D7, D12 and D20 showed AUCs of 0.82 [0.77; 0.87], 0.81 [0.75; 0.87] and 0.84 [0.75; 0.93]. Therefore, the final joint model provided adequate discrimination performances at D28 after collection of biomarker samples until D7, which improved as more samples were collected. After severe COVID‐19, decreased mHLA‐DR expression is associated with a greater risk of death at D28 independently of usual clinical confounders.
Using an early outcome as the sole source of information of interim decisions regarding treatment effect on a long‐term endpoint: The non‐Gaussian case
Authors: Garcia Barrado Leandro , Burzykowski Tomasz
Published: June 2024

In randomized clinical trials that use a long‐term efficacy endpoint, the follow‐up time necessary to observe the endpoint may be substantial. In such trials, an attractive option is to consider an interim analysis based solely on an early outcome that could be used to expedite the evaluation of treatment's efficacy. Garcia Barrado et al. (Pharm Stat. 2022; 21: 209–219) developed a methodology that allows introducing such an early interim analysis for the case when both the early outcome and the long‐term endpoint are normally‐distributed, continuous variables. We extend the methodology to any combination of the early‐outcome and long‐term‐endpoint types. As an example, we consider the case of a binary outcome and a time‐to‐event endpoint. We further evaluate the potential gain in operating characteristics (power, expected trial duration, and expected sample size) of a trial with such an interim analysis in function of the properties of the early outcome as a surrogate for the long‐term endpoint.
Balancing act: Trade‐offs and synergies within Sustainable Development Goals 1st, 10th, and 13th—Poverty, inequality, and climate actions
Authors: Khan Salim , Yuan Hongping , Hussain Muttahir
Published: June 2024

While the existing body of research has exhaustively examined several Sustainable Development Goals (SDGs), it fails to adequately reflect the significance of trade‐offs and synergies among the SDGs. This study aims to address the existing gap by doing a complete analysis of the SDGs in developing nations, specifically examining the trade‐off relationship between SDG‐1, pertaining to poverty reduction; SDG‐10, concerning reducing inequality; and SDG‐13, focusing on environmental activities. The analysis encompasses a sample of 40 developing countries. To accomplish this, a Generalized Method of Movement (GMM)‐style Panel‐Vector Autoregressive (PVAR) model is utilized, with carbon emissions (CO2Em) serving as a measure for environmental volatility. The findings confirm the existence of the Environmental Phillips Curve (EPC), which signifies a trade‐off between SDG‐1 (poverty), SDG‐10th (inequality), and SDG‐13th (CO2Em). Additionally, the processes of industrialization, trade, and population expansion have adverse effects on the attainment of SDG‐13. Conversely, industrialization and trade can contribute positively towards SDG‐1. A conventional sys‐GMM model is utilized for the robustness check, supporting the main findings acquired from the GMM‐style PVAR model. Lastly, based on empirical findings, significant policy implications are suggested for the achievement of SGDs.
Fast‐track recovery after surgery for perforated peptic ulcer safely shortens hospital stay: A systematic review and meta‐analysis of six randomized controlled trials and 356 patients
Authors: Zeyara Adam , Thomasson Jacob , Andersson Bodil , Tingstedt Bobby
Published: June 2024

Background

Postoperative management after surgery for perforated peptic ulcer is still burdened by old traditions. All available data for fast‐track recovery in this setting are either very unspecific or underpowered. The aim of this study was to evaluate fast‐track recovery in this diagnosis‐specific context in a larger sample.

Methods

Electronic data sources were searched. Eligible studies were randomized controlled trials (RCTs) comparing fast‐track recovery and traditional management after surgery for perforated peptic ulcer in adults. A systematic review and meta‐analysis was performed. The Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines regulated the process. Quality and risk of bias assessments of individual RCTs were performed by means of the Let Evidence Guide Every New Decision criteria and the Cochrane risk‐of‐bias tool. Primary endpoints were length of hospital stay and risk of complications. Random or fixed effects modeling were applied as indicated. Outcomes were measured by mean difference and risk difference.

Results

Six RCTs with a total cohort of 356 patients were included. Results of our meta‐analysis showed significantly shortened length of hospital stay (mean difference −3.50 days [95% CI ‐4.51 to −2.49], p ≤ 0.00001), significantly less superficial and deep surgical‐site infections (risk differences −0.12 [95% CI −0.20, −0.05], p = 0.002 and −0.03 [95% CI −0.09, 0.03], and p = 0.032, respectively), and significantly fewer pulmonary complications (risk difference −0.10 [95% CI −0.17, −0.03], p = 0.004) in the fast‐track group.

Conclusion

This systematic review and meta‐analysis shows that fast‐track recovery after surgery for perforated peptic ulcer significantly shortened hospital stay in the studied cohort without increasing the risk of postoperative complications.
Monitoring GPS‐collared moose by ground versus drone approaches: efficiency and disturbance effects
Authors: Mayer Martin , Furuhovde Erlend , Nordli Kristoffer , Myriam Ausilio Giorgia , Wabakken Petter , Eriksen Ane , Evans Alina L. , Mathisen Karen Marie , Zimmermann Barbara
Published: June 2024

Efficient wildlife management requires precise monitoring methods, for example to estimate population density, reproductive success, and survival. Here, we compared the efficiency of drone (equipped with a RGB camera) and ground approaches to detect and observe GPS‐collared female moose Alces alces and their calves. We also quantified how drone (n = 42) and ground (n = 41) approaches affected moose behavior and space use (n = 24 individuals). The average time used for drone approaches was 17 min compared to 97 min for ground approaches, with drone detection probability being higher (95% of adult female moose and 88% of moose calves) compared to ground approaches (78% of adult females and 82% of calves). Drone detection success increased at lower drone altitudes (50–70 m). Adult female moose left the site in 35% of drone approaches (with > 40% of those moose becoming disturbed once the drone hovered < 50 m above ground) compared to 56% of ground approaches. We failed to find short‐term effects (3 h after approaches) of drone approaches on moose space use, but moose moved > fourfold greater distances and used larger areas after ground approaches (compared to before the approaches had started). Similarly, longer‐term (24 h before and after approaches) space use did not differ between drone approaches compared to days without known disturbance, but moose moved comparatively greater distances during days of ground approaches. In conclusion, we could show that drone approaches were highly efficient to detect adult moose and their calves in the boreal forest, being faster and less disturbing than ground approaches, making them a useful tool to monitor and study wildlife.
Die Medizininformatik-Initiative im Überblick – Aufbau einer Gesundheitsforschungsdateninfrastruktur in Deutschland
Authors: Semler Sebastian C. , Boeker Martin , Eils Roland , Krefting Dagmar , Loeffler Markus , Bussmann Jens , Wissing Frank , Prokosch Hans-Ulrich
Published: June 2024

Die vom Bundesministerium für Bildung und Forschung (BMBF) 2016–2027 geförderte Medizininformatik-Initiative (MII) schafft erfolgreich Grundlagen für die datenbasierte Medizin in Deutschland. Zur Stärkung der Lehre, Aus- und Fortbildung im Bereich der Medizininformatik und zur Kompetenzverbesserung in den medizinischen Datenwissenschaften wurden im Rahmen dieser Förderung 51 neue Professuren, 21 wissenschaftliche Nachwuchsgruppen und verschiedene neue Studiengänge eingerichtet. Eine die gesamte Universitätsmedizin und ihre Partner umfassende gemeinsame dezentral föderierte Forschungsdateninfrastruktur wurde in Gestalt der Datenintegrationszentren (DIZ) an allen Standorten und dem Deutschen Forschungsdatenportal für Gesundheit (FDPG) als zentralem Zugangspunkt geschaffen. Für die Sekundärnutzung von Behandlungsdaten wurde ein modularer Kerndatensatz (KDS) definiert und unter konsequenter Nutzung internationaler Standards (z. B. FHIR, SNOMED CT, LOINC) implementiert. Als Rechtsgrundlage wurde eine behördlich genehmigte bundesweite breite Einwilligung (Broad Consent) eingeführt. Erste Datenausleitungen und Datennutzungsprojekte sind durchgeführt worden, eingebettet in eine übergeordnete Nutzungsordnung und standardisierte vertragliche Regelungen. Die Weiterentwicklung der MII-Gesundheitsforschungsdateninfrastrukturen im kooperativen Rahmen des Netzwerks Universitätsmedizin (NUM) bietet einen hervorragenden Ausgangspunkt für einen deutschen Beitrag zum kommenden Europäischen Gesundheitsdatenraum (EHDS), der Chancen für den Medizinforschungsstandort Deutschland eröffnet.
Eine retrospektive Identifikation von Schwerverletzten mittels ICD-10-Diagnosen
Authors: Neubert Anne , Hempe Sebastian , Gontscharuk Veronika , Jaekel Carina , Windolf Joachim , Kollig Erwin , Gäth Catharina ,   LeAf Trauma Study Group, Bieler Dan
Published: June 2024

Hintergrund

Durch eine stetige Verbesserung in der Behandlung überleben immer mehr Schwer- und Schwerstverletzte. Die Komplexität der Verletzungsmuster dieser Patient*innen bedingt, dass diese nur schwer in Routinedaten abbildbar sind.

Ziel der Arbeit

Das Ziel der Auswertung war es, International Statistical Classification of Diseases and Related Health Problems (ICD-10)-Diagnosen, welche eine Assoziation mit einem Injury Severity Score (ISS) ≥ 16 aufweisen und somit zur Operationalisierung von Schwerverletzten in Routinedaten genutzt werden könnten, zu identifizieren.

Material und Methoden

Es wurden die kodierten vierstelligen ICD-10-S-Diagnosen und der errechnete ISS von Traumapatienten des Bundeswehrzentralkrankenhauses Koblenz (BwZKrhs) und des Universitätsklinikums Düsseldorf (UKD) mittels statistischer Assoziationsmaße (Phi und Cramers V), linearer Regressionen sowie Methoden des Machine Learning (wie beispielsweise Random Forrest) analysiert.

Ergebnisse

Es konnten S‑Diagnosen zu Gesichts‑, Kopf‑, Thorax- und Beckenverletzungen, die mit einem ISS ≥ 16 assoziiert waren, identifiziert werden. Manche S‑Diagnosen zeigten nur in einem der beiden Datensätze eine Assoziation mit einem ISS ≥ 16. Ebenso fanden sich assoziierte Gesichts‑, Kopf‑, Thorax- und Beckenverletzungen in der Subgruppenanalyse der 18- bis 55-Jährigen.

Diskussion

Die aktuellen Auswertungen zeigen, dass es möglich ist, ICD-10-S-Diagnosen, welche eine signifikante Assoziation zu einem ISS ≥ 16 aufweisen, zu identifizieren. Gemäß dem Jahresbericht des TR-DGU® sind insbesondere in den Regionen Kopf und Thorax häufig Verletzungen mit einem Abbreviated Injury Scale Wert von ≥ 3 (AIS ≥ 3) zu finden.

Graphic abstract
Unconditional cash transfer programs and women’s empowerment: evidence from Pakistan
Authors: Heaton Chris , Kashif Asma , Mukhopadhaya Pundarik
Published: June 2024

This study explores the impact of unconditional cash transfers on the multiple dimensions of women’s empowerment in Pakistan. Emphasizing the importance of cultural and religious norms, empowerment is considered as a latent construct manifested through three distinct choice dimensions, viz., “self,” “familial,” and “economic.” For the empirical estimation, a structural equation model is used on the country-representative Impact Evaluation Survey data of 2015–16 for the Benazir Income Support Program. The measurement model identifies various indicators for the dimensions considered. The results confirm the importance of providing cash transfers to the country's poorest women in all three dimensions, while the impact on self-choices is almost 40% that of the impact on the other two aspects of empowerment. Our findings provide recommendations for the successful implementation of social assistance programs.
Resolving spatial response heterogeneity in glioblastoma
Authors: Ziegenfeuter Julian , Delbridge Claire , Bernhardt Denise , Gempt Jens , Schmidt-Graf Friederike , Hedderich Dennis , Griessmair Michael , Thomas Marie , Meyer Hanno S , Zimmer Claus , Meyer Bernhard , Combs Stephanie E , Yakushev Igor , Metz Marie-Christin , Wiestler Benedikt
Published: June 2024

Purpose

Spatial intratumoral heterogeneity poses a significant challenge for accurate response assessment in glioblastoma. Multimodal imaging coupled with advanced image analysis has the potential to unravel this response heterogeneity.

Methods

Based on automated tumor segmentation and longitudinal registration with follow-up imaging, we categorized contrast-enhancing voxels of 61 patients with suspected recurrence of glioblastoma into either true tumor progression (TP) or pseudoprogression (PsP). To allow the unbiased analysis of semantically related image regions, adjacent voxels with similar values of cerebral blood volume (CBV), FET-PET, and contrast-enhanced T1w were automatically grouped into supervoxels. We then extracted first-order statistics as well as texture features from each supervoxel. With these features, a Random Forest classifier was trained and validated employing a 10-fold cross-validation scheme. For model evaluation, the area under the receiver operating curve, as well as classification performance metrics were calculated.

Results

Our image analysis pipeline enabled reliable spatial assessment of tumor response. The predictive model reached an accuracy of 80.0% and a macro-weighted AUC of 0.875, which takes class imbalance into account, in the hold-out samples from cross-validation on supervoxel level. Analysis of feature importances confirmed the significant role of FET-PET-derived features. Accordingly, TP- and PsP-labeled supervoxels differed significantly in their 10th and 90th percentile, as well as the median of tumor-to-background normalized FET-PET. However, CBV- and T1c-related features also relevantly contributed to the model’s performance.

Conclusion

Disentangling the intratumoral heterogeneity in glioblastoma holds immense promise for advancing precise local response evaluation and thereby also informing more personalized and localized treatment strategies in the future.
Biparametric versus multiparametric MRI for the detection of clinically significant prostate cancer in a diverse, multiethnic population
Authors: Abramson Max , DeMasi Matthew , Zhu Denzel , Hines Laena , Lin Wilson , Kanmaniraja Devaraju , Chernyak Victoria , Agalliu Ilir , Watts Kara L.
Published: June 2024

Purpose

There is not yet satisfactory performance data comparing multiparametric MRI (mpMRI) versus biparametric MRI (bpMRI) for detecting prostate cancer (PCa), particularly in high-risk populations. We compared both protocols for detecting overall PCa and clinically significant PCa (CS-PCa; defined as Grade Group ≥ 2) in a multiethnic urban population.

Methods

We retrospectively reviewed electronic medical record data from men who underwent image-guided fusion prostate biopsy (FB) between 2016 and 2021 at our institution. Patient characteristics, Prostate Imaging Reporting and Data System (PI-RADS) scores, and FB outcomes were analyzed based on MRI protocol. Multivariate mixed-effects logistic regression models were used to examine associations of bpMRI versus mpMRI for detecting overall PCa and CS-PCa in targeted lesions, among all patients and stratified by race/ethnicity.

Results

Overall, 566 men (44.0% Non-Hispanic Black [NHB]; 27.0% Hispanic) with 975 PI-RADS 3–5 lesions on MRI underwent FB. Of these, 312 (55%) men with 497 lesions underwent mpMRI and 254 (45%) men with 478 lesions underwent bpMRI. On multivariate analyses among all men, the odds of detecting overall PCa (OR = 1.18, 95% CI: 1.05–3.11, p = 0.031) and CS-PCa (OR = 2.15, 95% CI: 1.16–4.00, p = 0.014) on FB were higher for lesions identified on bpMRI than mpMRI. When stratified by race/ethnicity, the odds of detecting overall PCa (OR = 1.86; p = 0.15) and CS-PCa (OR = 2.20; p = 0.06) were not statistically different between lesions detected on bpMRI or mpMRI.

Conclusion

BpMRI has similar diagnostic performance to mpMRI in detecting overall and CS-PCa within a racially/ethnically diverse population. BpMRI can be utilized for evaluating suspected CS-PCa among NHB and Hispanic men.
Bosea rubneri sp. nov. Isolated from Organically Grown Allium cepa
Authors: Stoll Dominic A. , Grimmler Christina , Hetzer Birgit , Masoura Alexandra , Kulling Sabine E. , Huch Melanie
Published: June 2024

Strain ZW T0_25T was isolated from an onion sample (Allium cepa var. Hytech F1) within a storage trial and proofed to be a novel, aerobic, Gram-stain negative, rod-shaped bacterial strain. Analyses of the 16S rRNA gene sequence and of the whole draft genome sequences, i.e., digital DNA–DNA hybridization (dDDH), Average Nucleotide Identity (ANI) and Average Amino Acid Identity (AAI) showed that this strain represents a new species of the genus Bosea. The genome size of strain ZW T0_25T is 6.19 Mbp, and the GC content is 66.9%. As whole cell sugars, rhamnose, ribose and glucose were identified. Ubiquinone Q-10 is the major respiratory quinone with 97.8%. Polar lipids in strain ZW T0_25T are composed of one phosphatidylethanolamine, one phosphatidylglycerol, one aminophospholipid, two aminolipids, one glycolipid and two phospholipids whereas the fatty acid profile predominantly consists of C18:1 w7c (63.3%), C16:1 w7c (19.5%) and C16:0 (7.1%). Phenotypic traits were tested in the wet lab as well as predicted in silico from genome data. Therefore, according to this polyphasic approach, the new name Bosea rubneri sp. nov. with the type strain ZW T0_25T (= DSM 116094 T = LMG 33093 T) is proposed.
Robust combinatorial optimization problems under budgeted interdiction uncertainty
Authors: Goerigk Marc , Khosravi Mohammad
Published: June 2024

In robust combinatorial optimization, we would like to find a solution that performs well under all realizations of an uncertainty set of possible parameter values. How we model this uncertainty set has a decisive influence on the complexity of the corresponding robust problem. For this reason, budgeted uncertainty sets are often studied, as they enable us to decompose the robust problem into easier subproblems. We propose a variant of discrete budgeted uncertainty for cardinality-based constraints or objectives, where a weight vector is applied to the budget constraint. We show that while the adversarial problem can be solved in linear time, the robust problem becomes NP-hard and not approximable. We discuss different possibilities to model the robust problem and show experimentally that despite the hardness result, some models scale relatively well in the problem size.
Laboratory features and pharmacological management of early and late-onset primary Sjögren’s syndrome
Authors: Saleem Rimah A. , Ramadan Majed , Elshaaer Yasmin , Sukkarieh Hatouf , Alissa Rasha , Alhusseini Noara , Tamim Hani , Alshahrani Awad , Almaimoni Hesham
Published: June 2024

Background

Primary Sjögren’s Syndrome (pSS) is a systemic chronic autoimmune disorder that contributes to dry mouth (xerostomia) and eyes (xerophthalmia). It mainly affects females between 40 and 60 years old. So far, there is no treatment to cure SS; however, there is a list of medications that can ameliorate the symptoms. In addition, there has been no single test until now to detect pSS, but clinical and immunological investigations are applied as diagnostic tools. Therefore, this study aimed to explore the characteristics of pSS in Saudi patients based on the onset of the disease through laboratory findings and pharmaceutical management.

Methodology

This retrospective study examined diagnosed patients with pSS between 2018 and 2023 from the National Guard Hospital, Saudi Arabia. Data of pSS patients was categorized into two groups: early (under 40 years old) and late-onset (40 years old and above). Data on demographic information, mortality rate, and blood tests such as complete blood count (CBC), creatinine, erythrocyte sedimentation rate (ESR), and vitamin levels, in addition to prescribed medications, were collected from the patient’s medical record. Chi-square and t-tests were mainly used, and statistical significance was determined at a P-value less than 0.05.

Results

A total of 453 patients were included in the study, where the early-onset group comprised 136 and the late-onset group comprised 317 patients. The mean age of the early and late onset was 34.2 and 60.4, respectively. ESR was significantly higher in the early (46.3 mm/hr) and late-onset (49.8 mm/hr). The most common medication used by all pSS patients was hydroxychloroquine. However, artificial tears were mainly observed in the late-onset group. Other medications, such as pilocarpine, methotrexate, and azathioprine, were prescribed to pSS patients to a lesser extent.

Conclusion

This study suggests that the onset of pSS could occur even before the age of 40 among Saudi citizens. Notably, elevated ESR levels appeared to be a feature of pSS, which was consistent with other previous findings. The variability of some medications between early-onset and late-onset pSS may indicate disease progression. However, further investigations are required to confirm this observation.
Comparison of scales for the evaluation of aneurysmal subarachnoid haemorrhage: a retrospective cohort study
Authors: Couret David , Boussen Salah , Cardoso Dan , Alonzo Audrey , Madec Sylvain , Reyre Anthony , Brunel Hervé , Girard Nadine , Graillon Thomas , Dufour Henry , Bruder Nicolas , Boucekine Mohamed , Meilhac Olivier , Simeone Pierre , Velly Lionel
Published: June 2024

Background/Objectives

Aneurysmal subarachnoid haemorrhage (aSAH) is a life-threatening event with major complications. Delayed cerebral infarct (DCI) occurs most frequently 7 days after aSAH and can last for a prolonged period. To determine the most predictive radiological scales in grading subarachnoid or ventricular haemorrhage or both for functional outcome at 3 months in a large aSAH population, we conducted a single-centre retrospective study.

Methods

A 3-year single-centre retrospective cohort study of 230 patients hospitalised for aSAH was analysed. Initial computed tomography (CT) scans in patients hospitalised for aSAH were blindly assessed using eight grading systems: the Fisher grade, modified Fisher grade, Barrow Neurological Institute scale, Hijdra scale, Intraventricular Haemorrhage (IVH) score, Graeb score and LeRoux score.

Results

Of 200 patients with aSAH who survived to day 7 and were included for DCI analysis, 39% of cases were complicated with DCI. The Hijdra scale was the best predictor for DCI, with a receiver operating characteristic area under the curve (ROCAUC) of 0.80 (95% confidence interval (CI), 0.74–0.85). The IVH score was the most effective grading system for predicting acute hydrocephalus, with a ROCAUC of 0.85 (95% CI, 0.79–0.89). In multivariate analysis, the Hijdra scale was the best predictor of the occurrence of DCI (hazard ratio, 1.18; 95% CI, 1.10–1.25).

Conclusions

Although these results have yet to be prospectively confirmed, our findings suggest that the Hijdra scale may be a good predictor of DCI and could be useful in daily clinical practice.

Clinical relevance statement

Better assessment of subarachnoid haemorrhage patients would allow for better prognostication and management of expectations, as well as referral for appropriate services and helping to appropriate use limited critical care resources.

Key Points

Aneurysmal subarachnoid haemorrhage is a life-threatening event that causes severe disability and leads to major complications such as delayed cerebral infarction.

Accurate assessment of the amount of blood in the subarachnoid spaces on computed tomography with the Hijdra scale can better predict the risk of delayed cerebral infarct.

The Hijdra scale could be a good triage tool for subarachnoid haemorrhage patients.
Robust change-point detection for functional time series based on U-statistics and dependent wild bootstrap
Authors: Wegner Lea , Wendler Martin
Published: June 2024

The aim of this paper is to develop a change-point test for functional time series that uses the full functional information and is less sensitive to outliers compared to the classical CUSUM test. For this aim, the Wilcoxon two-sample test is generalized to functional data. To obtain the asymptotic distribution of the test statistic, we prove a limit theorem for a process of U-statistics with values in a Hilbert space under weak dependence. Critical values can be obtained by a newly developed version of the dependent wild bootstrap for non-degenerate 2-sample U-statistics.
A computational approach to integrate three-dimensional peridynamics and two-dimensional higher-order classical elasticity theory for fracture analysis
Authors: Zhang Jing , Enea Marco , Pagani Alfonso , Carrera Erasmo , Madenci Erdogan , Liu Xia , Yang Qingsheng
Published: June 2024

As a nonlocal alternative of classical continuum theory, peridynamics (PD) is mathematically compatible to discontinuities, making it particularly attractive for failure prediction. The PD theory on the other side can be computationally demanding due to its nonlocal interactions. A coupling between PD and refined higher-order finite element method (FEM) integrates their salient features. The present study proposes a computational approach to couple three-dimensional peridynamics with two-dimensional higher-order finite elements based on classical elasticity. The bond-based PD modeling is considered in a region where damage might appear while refined finite element modeling is used for the remaining region. The refined finite elements employed in this study are based on the 2D Carrera Unified Formulation (CUF), which provides 3D-like accuracy with optimized computational efficiency. The coupling between PD and FEM is achieved through the Lagrange multiplier method which permits physical consistency and compatibility at the interface domain. An adaptive convergence check algorithm is also proposed to achieve predetermined accuracy in the solution with minimum computational effort. Simulations of quasi-static tension tests, wedge splitting tests and L-plate cracking tests are carried out for verification. In-depth analysis shows that the present approach can reproduce the linear deformation, material degradation and crack propagation in an effective way.
Full-field validation of finite cell method computations on wire arc additive manufactured components
Authors: Tröger Jendrik-Alexander , Sartorti Roman , Garhuom Wadhah , Düster Alexander , Hartmann Stefan
Published: June 2024

Wire arc additive manufacturing enables the production of components with high deposition rates and the incorporation of multiple materials. However, the manufactured components possess a wavy surface, which is a major difficulty when it comes to simulating the mechanical behavior of wire arc additively manufactured components and evaluation of experimental full-field measurements. In this work, the wavy surface of a thick-walled tube is measured with a portable 3D scanning technique first. Then, the surface contour is considered numerically using the finite cell method. There, hierarchic shape functions based on integrated Legendre polynomials are combined with a fictitious domain approach to simplify the discretization process. This enables a hierarchic p-refinement process to study the convergence of the reaction quantities and the surface strains under tension–torsion load. Throughout all considerations, uncertainties arising from multiple sources are assessed. This includes the material parameter identification, the geometry measurement, and the experimental analysis. When comparing experiment and numerical simulation, the in-plane surface strains are computed based on displacement data using radial basis functions as ansatz for global surface interpolation. It turns out that the finite cell method is a suitable numerical technique to consider the wavy surface encountered for additively manufactured components. The numerical results of the mechanical response of thick-walled tubes subjected to tension–torsion load demonstrate good agreement with real experimental data, particularly when employing higher-order polynomials. This agreement persists even under the consideration of the inherent uncertainties stemming from multiple sources, which are determined by Gaussian error propagation.