bluuebunny/crossref_metadata_2025 huggingface dataset:
Water‐Triggered Segment Orientation of Long‐Lasting Anti‐Biofouling Polyurethane Coatings on Biomedical Catheters via Solvent Exchange Strategy
Authors: Zhang Zhenyan , Wang Lei , Liu Jiaying , Yu Huan , Zhang Xu , Yin Jinghua , Luan Shifang , Shi Hengchong
Published: June 2023

The formation of biofilm and thrombus on medical catheters poses a significant life‐threatening concern. Hydrophilic anti‐biofouling coatings upon catheter surfaces with complex shapes and narrow lumens are demonstrated to have the potential in reducing complications. However, their effectiveness is constrained by poor mechanical stability and weak substrate adhesion. Herein, a novel zwitterionic polyurethane (SUPU) with strong mechanical stability and long‐term anti‐biofouling is developed by controlling the ratio of sulfobetaine‐diol and ureido‐pyrimidinone. Once immersed in water, as‐synthesized zwitterionic coating (SUPU3 SE) would undergo a water‐driven segment reorientation to obtain much higher durability than its direct drying one, even under various extreme treatments, including acidic solution, abrasion, ultrasonication, flushing, and shearing, in PBS at 37 °C for 14 days. Moreover, SUPU3 SE coating could achieve a 97.1% of exceptional reducing protein fouling, complete prevention of cell adhesion, and long‐lasting anti‐biofilm performance even after 30 days. Finally, the good anti‐thrombogenic formations of SUPU3 SE coating with bacterial treatment are validated in blood circulation through an ex vivo rabbit arteriovenous shunt model. This work provides a facile approach to fabricating stable hydrophilic coating through a simple solvent exchange to reduce thrombosis and infection of biomedical catheters.
Chiral 1D Hybrid Metal Halides with Piezoelectric Energy Harvesting and Sensing Properties
Authors: An Lian-Cai , Zhao Chen , Zhao Ying , Zhang Ying , Li Kai , Stroppa Alessandro , Li Wei , Bu Xian-He
Published: June 2023

Chiral hybrid metal halides have been widely studied in the field of photondetectors, chiral optics, and spintronics due to their great structural flexibility and suitable bandgaps. Inspired by such great progress made in the abovementioned fields, continuous efforts need to be paid to seek other interesting applications for chiral hybrid metal halides. Herein, the synthesis of a pair of one‐dimensional enantiomorphic hybrid metal halide piezoelectrics, R/SMPCdCl4(R/SMP = R/S‐2‐methylpiperazine), and their applications in piezoelectric energy harvesting and sensing are reported. Density functional theory calculations show that these chiral piezoeletrics possess low elastic properties and high piezoelectric constants (16.71, 8.39, and 7.35 pC N−1). In addition, devices made of RMPCdCl4/PDMS (PDMS = polydimethylsiloxane) composite films are fabricated for piezoelectric energy harvesting and sensing. The piezoelectric energy harvesters with optimized content of 15 wt% RMPCdCl4/PDMS show not only excellent performance with an open‐circuit voltage of 2.57 V, short‐circuit current of 0.37 μA, and power density of 0.55 μW cm−2 but also outstanding stability of more than 3500 cycles. Meanwhile, these piezoelectric energy harvesters exhibit prominent sensing properties for detecting tapping, finger bending, walking, and running. It is demonstrated that chiral hybrid metal halides hold great potential in intelligent wearable and sensing devices.
Mechanical properties and constitutive model of the buckling restraint rebar under compression loads
Authors: Jia Junfeng , Zhao Nannan , Bai Yulei , Cao Yanhui , Cheng Shoushan , Fan Ping
Published: June 2023

Buckling of the longitudinal rebar is one of the main forms of plastic hinge failure in reinforced concrete (RC) columns after an earthquake. This rebar buckling significantly impacts the seismic bearing capacity and energy dissipation capacity. To restrain the development of longitudinal rebar buckling behavior and delay the degradation of lateral strength in RC columns, this paper developed a new type of buckling restraint rebar (BRR) consisting of three components: longitudinal rebar, a restraint sleeve, and foam material. First, the BRR mechanical properties under compression and tension‐compression cyclic loading were obtained through quasi‐static loading tests. Then, the BRR compression and tension‐compression cyclic loading processes were numerically simulated based on ABAQUS finite element software. The simulated results were compared with the test results. Finally, a stress–strain constitutive model for this new BRR was proposed based on this study. Results showed that the restraint sleeve could significantly enhance the lateral stiffness and the bearing capacity of longitudinal reinforcement after yielding. The compressive performance of BRR was mainly affected by the length and wall thickness of the sleeve. The cyclic performance was mainly affected by the length of the sleeve and the clearance between the sleeve and the reinforcement. The BRR constitutive model proposed in this paper can accurately reflect the influence of restraint sleeves on the stiffness of longitudinal reinforcement after yielding.
Enhanced High Power Impulse Magnetron Sputter Processes
Authors: Gaines J. R.
Published: June 2023

High power impulse magnetron sputtering (HIPMS) has emerged as a useful approach for depositing highly dense and smooth coatings of electrically conductive materials. Recent advances in power supply technology have further enabled HIPMS through the addition of a positive kick in the pulse cycle which supplies a bias at the surface of the sputter target which expels sputter target ions and sends more charged adatoms toward the substrate. This has been demonstrated with critical materials like diamond‐like carbon and plasmonic materials. Material specific pulse magnitudes and durations can be developed to achieve new novel thin film morphologies.
Triple combination of lomustine, temozolomide and irradiation reduces canine glioma cell survival in vitro
Authors: Fuchs Daniel , Rohrer Bley Carla , Morandi Luca , Tonon Caterina , Weyland Mathias S. , Nytko Katarzyna J.
Published: June 2023

Background

Combined chemoradiation offers a promising therapeutic strategy for dogs with glioma. The alkylating agents temozolomide (TMZ) and lomustine (CCNU) penetrate the blood‐brain barrier, and doses for dogs are established. Whether such combinations are clinically advantageous remains to be explored together with tumour‐specific markers.

Objective

To investigate if triple combination of lomustine, temozolomide and irradiation reduces canine glioma cell survival in vitro.

Methods

We evaluated the sensitising effect of CCNU alone and in combination with TMZ‐irradiation in canine glioma J3T‐BG cells and long‐term drug‐exposed subclones by using clonogenic survival and proliferation assays. Bisulphite‐SEQ and Western Blot were used to investigate molecular alterations.

Results

TMZ (200 μM) or CCNU alone (5 μM) reduced the irradiated survival fraction (4 Gy) from 60% to 38% (p = 0.0074) and 26% (p = 0.0002), respectively. The double‐drug combination reduced the irradiated survival fraction (4 Gy) more potently to 12% (p < 0.0001).

After long‐term drug exposure, both subclones show higher IC50 values against CCNU and TMZ. For CCNU‐resistant cells, both, single‐drug CCNU (p = 0.0006) and TMZ (p = 0.0326) treatment combined with irradiation (4 Gy) remained effective. The double‐drug‐irradiation combination reduced the cell survival by 86% (p < 0.0001), compared to 92% in the parental (nonresistant) cell line. For TMZ‐resistant cells, only the double‐drug combination with irradiation (4 Gy) reduced the cell survival by 88% (p = 0.0057) while single‐drug treatment lost efficacy.

Chemoresistant cell lines demonstrated higher P‐gp expression while MGMT‐methylation profile analysis showed a general high methylation level in the parental and long‐term treated cell lines.

Conclusions

Our findings indicate that combining CCNU with TMZ‐irradiation significantly reduces canine glioma cell survival. Such a combination could overcome current challenges of therapeutic resistance to improve overall patient survival.
On‐farm myringotomy as treatment for persistent otitis media in five Dutch veal calves
Authors: van de Mheen Robert
Published: June 2023

Otitis media (presumably caused by Mycoplasma bovis) is a frequently encountered problem with big economic implications in the Dutch veal calf industry. Conservative treatment using antibiotics, NSAIDs and corticosteroids is regularly unsuccessful. The affected calves usually start to waste due to pain and decreased feed intake. This report describes a novel treatment option, performing a myringotomy (surgical opening of the eardrum), combined with local antibiotic and corticosteroid therapy. The outcome was positive; in four out of five calves, the clinical signs resolved within 3 weeks after intervention. On‐farm myringotomy is a promising treatment option in persistent otitis media.
Bat use of abandoned mines throughout Nevada
Authors: Moran Megan L. , Steven Janet C. , Williams Jason A. , Sherwin Richard E.
Published: June 2023

Abandoned mines offer important roosting habitat for several species of bats throughout the western United States. Currently, abandoned mine reclamation programs are tasked with closing abandoned mines to ameliorate safety, health, and environmental hazards found in and around these sites. Without appropriate pre‐closure evaluations to determine use of mine workings prior to closure, bats that depend on abandoned mines may be negatively impacted. To mitigate impacts of abandoned mine reclamation on bats, surveyors typically conduct pre‐closure biological evaluations and recommend wildlife compatible closures (e.g., bat gates) for ecologically important sites. Due to hazardous conditions found in many abandoned mines, internal surveys cannot always be conducted, and external surveys are not reliable for determining underground habitat or inferring past, future, or potential use of mines by bats when they are absent during external surveys. The purpose of our study was to use internal mine surveys to examine relationships between abandoned mine use by bats and characteristics of the mine and landscape, including portal area and shape, number of portals, mine depth, elevation, proximity to water and land use type. We found that surface features including land use type, distance to water, and elevation were associated with bat use, as were several mine features including depth of workings and portal shape. To best conserve sensitive species of bats, it is essential that pre‐closure biological evaluations be as detailed as possible to enhance biological understanding of species' roosting associations and distribution throughout the landscape. Further information will best facilitate development of ecologically sound closure recommendations for abandoned mine openings.
Classroom Learning Environments and Assessment Practices in Science Classrooms in Western Australia
Authors: Koul Rekha B.
Published: June 2023

The research described in this paper was aimed at identifying exemplary assessment practices in secondary science classes. In the first stage, following a review of the literature, a six-scale instrument of 48 items was trialed with a sample of 470 students from grades eight, nine and ten in 20 science classrooms in three Western Australian schools. Based on internal consistency reliability data and exploratory factor analysis, refinement decisions resulted in a five-scale instrument that was named the Student Perceptions of Assessment Questionnaire (SPAQ). In the second stage, the SPAQ was used with an attitude scale, and a self-efficacy scale. This survey was administered to a larger sample of 960 students from 40 science classes from the same grades as in the first stage. Statistical analyses confirmed the validity and reliability of the SPAQ. Based on the results of this survey exemplary teachers were identified. In the third and last stage interviews with teachers and students were conducted. Classes of these exemplary teachers were also observed. These exemplary teachers were found to be thorough in their teaching, giving students enough time to prepare for the assessment, giving students freedom to choose from a variety of assessments and were flexible in teaching and assessment. They also demonstrated in-depth understanding of the science topics they were teaching.
Affective Student–Teacher Relationships and Students’ Engagement: A Cross–Cultural Comparison of China and The Netherlands
Authors: Roorda Debora , Chen Mengdi , Zee Marjolein
Published: June 2023

Ample evidence has been found for the association between affective, dyadic student–teacher relationships and students’ engagement with schoolwork in Western, individualistic countries. There are far fewer studies, however, examining this association in Eastern, collectivistic countries. As maintaining harmony in interpersonal relationships plays a crucial role in collectivistic countries, student–teacher relationships may even be more important in collectivistic countries than in individualistic countries. In the present study, we therefore investigated cross–cultural differences in the strength of associations between student–teacher relationship quality and students’ engagement based on data from the Netherlands (a Western country) and China (an Eastern country). The Dutch sample included 789 students (51.1% girls) and the Chinese sample included 588 students (52.9% girls) from grades 3 to 6 of elementary school. Students reported about the quality of their relationship with their teacher (closeness, conflict) and their behavioral and emotional engagement with schoolwork. Hierarchical linear modeling showed that the positive association between closeness and both behavioral and emotional engagement was stronger for the Chinese sample than for the Dutch sample. In contrast, the negative association between conflict and both behavioral and emotional engagement did not differ across countries. To conclude, closeness may be more relevant for Chinese students’ engagement than would be expected based on Western studies, whereas conflict seems to be equally harmful in both cultures. Therefore, developing relationship-focused interventions for Chinese teachers and students seems important, either by adapting Western programs or by developing new programs especially designed for Chinese schools.
Effective Interpersonal Relationships: On the Association Between Teacher Agency and Communion with Student Outcomes
Authors: den Brok Perry , van Tartwijk Jan , Mainhard Tim
Published: June 2023

This chapter reviews research that has investigated the link between teacher-student interpersonal relationships and student outcomes. First, prior research reviews investigating the relationship between these two sets of variables is discussed. Such research overwhelmingly shows the importance of warm and supportive relationships for both cognitive and affective outcomes, with affective outcomes also acting as an intermediary between the other two variables. Next, interpersonal theory is discussed, that conceptualizes interpersonal relationships from a systems perspective and distinguishes between the communion and agency dimensions of relationships. At the end of the contribution, research is reviewed that has used interpersonal theory as its leading framework and that has mapped students’ perceptions of interpersonal relationships with one particular instrument, the Questionnaire on Teacher Interaction (QTI). Findings show that both interpersonal dimensions are positively related to cognitive as well as affective outcomes, either jointly or separately, with agency being more strongly related to cognitive outcomes and communion being more strongly related to affective outcomes.
The Effects of a Short Self-Access Online Training for Practicum Preparation on the Depths of Reflection of Preservice Teachers
Authors: Wang Ye , Ko James , Wang Peng
Published: June 2023

Enhancing preservice teachers’ critical reflections on their newly acquired knowledge and experience is crucial for promoting their teaching skills and performance. However, it is a challenging task to teach reflections and increase their depths of reflection. Previous research has succeeded to help preservice teachers reflect in a full-term taught course. However, little empirical research demonstrated the effects of a short self-access online training program on the depths of reflection of preservice teachers. Framed in Ryan and Ryan’s (High Educ Res Dev 32(2):244–257, 2013) reflection depth model, this study adopted a quasi-experimental research design to examine the depths of reflection after attending a short online training of four 30-min sessions varied in training session order and session content. Data of 555 reflective statements were identified subsequently in 120 reflective logs of 30 preservice teachers in a teacher education university in northern China. The results showed a significant difference between the experimental and control groups, indicating that a short self-access online training program has beneficial effects on preservice teachers’ reflections during practicum preparation. While the depths of the reflective statements identified were relatively shallow, the frequency of the reflective statements did not decrease with their depths. Additionally, topics in the online training sessions significantly affected the depths of preservice teachers’ reflections, while the training sequence did not. This study is conducive to designing the relevant online training programmes to promote the depths of reflection of preservice teachers in teacher education programmes.
Evaluating Effective Differentiated Instruction in Multicultural South African Secondary Schools
Authors: de Jager Thelma
Published: June 2023

Various contextual factors contribute to teachers’ failure to employ effective differentiated instruction in classroom practices. This is evident in the high drop-out rate of South African students. These students mostly attend schools in lower income and rural areas that are poorly resourced and where teachers are not always trained to support students and apply differentiated instruction in the classroom. The study aimed to establish from students’ observations and teachers’ perceptions to what extent differentiated instruction is employed in classrooms. Data was collected in public secondary schools (n = 25) of the Gauteng Province in South Africa, using a quantitative approach. The social context of these schools still embodies poverty, lack of educational opportunities and resources, and overcrowded classrooms (ratio 1:40). Two questionnaires were completed, one by secondary school students (n = 4510) and another by teachers (n = 424). Contradictions were detected when students’ observations of their teachers’ differentiated classroom practices were compared with their teachers’ perceptions. Findings showed that teachers did not always establish if students understood the content and did not always know what their difficulties were. The possible reasons could be inadequate training of teachers to identify students’ learning barriers and to create and implement differentiated activities; teachers experiencing a lack of time to complete the curriculum; a lack of resources; teaching large classes; and an inability to manage and maintain discipline in classes.
Differentiation and Students with Special Educational Needs: Teachers’ Intentions and Classroom Interactions
Authors: Kupers Elisa , de Boer Anke , Loopers Judith , Bakker Alianne , Minnaert Alexander
Published: June 2023

Differentiation is mainly linked to differences in learning capacities, but studenss differ in more domains: differences in motivation, behavior and special educational needs (SEN) are equally relevant. In line with the world-wide trend towards inclusive education, the aim of this chapter is to shed light on Dutch teachers’ intentions to differentiate, as well as possible differences in interactions between teachers and students with and without SEN in regular secondary vocational educational education. We first analyzed teachers’ online diary entries with regards to their intended differentiation practices for the next lesson. We coded what kind of intentions arise, the level of detail and quality of these intentions and to what kind of differentiation is referred (only cognitive, or possibly also differentiation on domains of behavior, motivation, or students with SEN). Second, we focused on one-to-one classroom interactions between teachers and students with and without special educational needs. We analyzed to what extent there are differences between the interactions of students with and without SEN in terms of teachers’ need-supportive teaching and students’ engagement. Together, these studies contribute to our understanding of differentiation intentions and practices with regards to meeting the needs of all students in diverse classrooms.
Towards closed-walled designs in topology optimization using selective penalization
Authors: Rieser Jasper , Zimmermann Markus
Published: June 2023

3D topology optimization using a density approach with penalization usually produces truss-like, open-walled structures. The coarser the mesh, the smaller the volume fraction, and the faster the penalization is increased, the more pronounced this effect tends to be. However, closed-walled designs are often more efficient and have other beneficial properties. For instance, closed walls can contribute to achieving self-supporting designs for additive manufacturing that potentially require fewer sacrificial support structures than truss-like designs. This paper presents a two-step optimization procedure for generating closed-walled designs using coarse meshes. The first step takes the usual Eulerian approach of performing a SIMP-based topology optimization on a fixed mesh. To keep thin geometrical features, like walls with a thickness below element size, penalization is switched off deliberately where the formation of such features is detected. Adopting a Lagrangian description, intermediate densities still present in the optimized design are subsequently eliminated in a second step by shrinking each element according to its density. By analogy with volumetric thermal contraction, this is accomplished by solving a fictitious thermo-elastic problem where the temperature has been replaced by a density expression. The outcome is a morphed mesh with a somewhat smoothed surface and a volume close to the specified material volume limit. This body-fitted representation of the design considerably simplifies the final conversion into a manufacturable CAD-type geometry. The two-step optimization procedure is applied to a cantilever, a torsion rod, and a disk reinforcement benchmark problem. Optimized designs are closed-walled and show very good agreement to those found for much finer meshes. Problem-specific stiffness improvements over truss-like designs between $$6\%$$

6
%

and almost $$30\%$$

30
%

were achieved and confirmed the findings previously reported by other authors.
Linear stability of a counter-rotating vortex pair approaching an inviscid wall
Authors: Herndon Mark A. , Jaworski Justin W.
Published: June 2023

The influence of an inviscid planar wall on the temporal development of the long-wavelength instability of a trailing vortex pair is formulated analytically and studied numerically. The center positions and deformation perturbations of the trailing vortices are marched forward in time via the vortex filament method based on Biot–Savart induction. An optimal perturbation analysis of the vortex system determines the wavenumber and initial condition that yield maximum perturbation growth for any instant in time. Direct integration of the vortex system highlights its sensitivity to initial conditions and the time dependence of the optimal wavenumber, which are not features of the classical free vortex pair. As the counter-rotating vortex pair approaches the wall, the wavenumber for maximum growth shifts to a higher value than what is predicted for the Crow instability of vortices in an unbounded fluid. The present analysis demonstrates that the local suppression of the Crow instability near a planar wall may be described without recourse to viscous fluid arguments.

Graphical abstract
Effects of sacubitril/valsartan on exercise capacity: a prognostic improvement that starts during uptitration
Authors: Mapelli Massimo , Mattavelli Irene , Paolillo Stefania , Salvioni Elisabetta , Magrì Damiano , Galotta Arianna , De Martino Fabiana , Mantegazza Valentina , Vignati Carlo , Esposito Immacolata , Dell’Aversana Simona , Paolillo Roberta , Capovilla Teresa , Tamborini Gloria , Nepitella Alessandro Alberto , Filardi Pasquale Perrone , Agostoni Piergiuseppe
Published: June 2023

Purpose

Sacubitril/valsartan is a mainstay of the treatment of heart failure with reduced ejection fraction (HFrEF); however, its effects on exercise performance yielded conflicting results. Aim of our study was to evaluate the impact of sacubitril/valsartan on exercise parameters and echocardiographic and biomarker changes at different drug doses.

Methods

We prospectively enrolled consecutive HFrEF outpatients eligible to start sacubitril/valsartan. Patients underwent clinical assessment, cardiopulmonary exercise test (CPET), blood sampling, echocardiography, and completed the Kansas City Cardiomyopathy Questionnaire (KCCQ-12). Sacubitril/valsartan was introduced at 24/26 mg b.i.d. dose and progressively uptitrated in a standard monthly-based fashion to 97/103 mg b.i.d. or maximum tolerated dose. Study procedures were repeated at each titration visit and 6 months after reaching the maximum tolerated dose.

Results

Ninety-six patients completed the study, 73 (75%) reached maximum sacubitril/valsartan dose. We observed a significant improvement in functional capacity across all study steps: oxygen intake increased, at peak exercise (from 15.6 ± 4.5 to 16.5 ± 4.9 mL/min/kg; p trend = 0.001), while minute ventilation/carbon dioxide production relationship reduced in patients with an abnormal value at baseline. Sacubitril/valsartan induced positive left ventricle reverse remodeling (EF from 31 ± 5 to 37 ± 8%; p trend < 0.001), while NT-proBNP reduced from 1179 [610–2757] to 780 [372–1344] pg/ml (p trend < 0.0001). NYHA functional class and the subjective perception of limitation in daily life at KCCQ-12 significantly improved. The Metabolic Exercise Cardiac Kidney Index (MECKI) score progressively improved from 4.35 [2.42–7.71] to 2.35% [1.24–4.96], p = 0.003.

Conclusions

A holistic and progressive HF improvement was observed with sacubitril/valsartan in parallel with quality of life. Likewise, a prognostic enhancement was observed.
Using patient-derived tumor organoids from common epithelial cancers to analyze personalized T-cell responses to neoantigens
Authors: Parikh Anup Y. , Masi Robert , Gasmi Billel , Hanada Ken-ichi , Parkhurst Maria , Gartner Jared , Sindiri Sivasish , Prickett Todd , Robbins Paul , Zacharakis Nikolaos , Beshiri Mike , Kelly Kathleen , Rosenberg Steven A. , Yang James C.
Published: June 2023

Adoptive cell transfer of tumor-infiltrating lymphocytes (TIL) can mediate durable complete responses in some patients with common epithelial cancers but does so infrequently. A better understanding of T-cell responses to neoantigens and tumor-related immune evasion mechanisms requires having the autologous tumor as a reagent. We investigated the ability of patient-derived tumor organoids (PDTO) to fulfill this need and evaluated their utility as a tool for selecting T-cells for adoptive cell therapy. PDTO established from metastases from patients with colorectal, breast, pancreatic, bile duct, esophageal, lung, and kidney cancers underwent whole exomic sequencing (WES), to define mutations. Organoids were then evaluated for recognition by autologous TIL or T-cells transduced with cloned T-cell receptors recognizing defined neoantigens. PDTO were also used to identify and clone TCRs from TIL targeting private neoantigens and define those tumor-specific targets. PDTO were successfully established in 38/47 attempts. 75% were available within 2 months, a timeframe compatible with screening TIL for clinical administration. These lines exhibited good genetic fidelity with their parental tumors, especially for mutations with higher clonality. Immunologic recognition assays demonstrated instances of HLA allelic loss not found by pan-HLA immunohistochemistry and in some cases WES of fresh tumor. PDTO could also be used to show differences between TCRs recognizing the same antigen and to find and clone TCRs recognizing private neoantigens. PDTO can detect tumor-specific defects blocking T-cell recognition and may have a role as a selection tool for TCRs and TIL used in adoptive cell therapy.
Impact of COVID‐19 Pandemic on Readmission Rates Following Colorectal Surgery: A Retrospective Cohort Study
Authors: Lemke Madeline , Allen Laura , Samarasinghe Nadeesha , Vogt Kelly , Brackstone Muriel , Zwiep Terry
Published: June 2023

Background

The COVID‐19 pandemic placed increased pressure to discharge patients early; this could have resulted in rushed discharges requiring patients to return to hospital. The impact of the pandemic on readmission after colorectal surgery is unknown.

Methods

The National Surgical Quality Improvement Program (ACS‐NSQIP) database was used to compare patients undergoing elective colorectal surgery in 2019 and 2020, prior to and during the COVID‐19 pandemic. Multivariable logistic regression was used to examine variables associated with readmission. Propensity score matching was then used to compare patients in the pre‐pandemic and pandemic cohorts.

Results

A total of 72,874 colorectal cases were included. There were 17.7% less cases in 2020. Rate of readmission was similar in both groups (9.6% vs. 9.4%). There were fewer patients discharged to a facility such as nursing facility or rehabilitation center in 2020, with more patients discharged home. Year was not associated with readmission on multivariable analysis. In the matched cohort, readmission rates did not differ (9.7% vs. 9.3% p = 0.129) nor did mortality (0.8% vs. 0.8% p = 0.686).

Conclusions

No difference in readmission rates before or during the COVID‐19 pandemic was observed; suggesting increased pressure to keep patients out of hospital in the COVID‐19 pandemic did not result in patients being rushed home requiring repeat admission. More patients were discharged home with fewer to rehabilitation or nursing facilities in 2020, suggesting success with avoiding transitional services in the right setting.
Adavosertib (AZD1775) does not prolong the QTc interval in patients with advanced solid tumors: a phase I open-label study
Authors: Någård Mats , Ah-See Mei-Lin , Strauss James , Wise-Draper Trisha , Safran Howard P. , Nadeau Laura , Edenfield William J. , Lewis Lionel D. , Rekić Dinko , Dota Corina , Ottesen Lone H. , Li Yan , Mugundu Ganesh M.
Published: June 2023

Purpose

Adavosertib is a small-molecule, ATP-competitive inhibitor of Wee1 kinase. Molecularly targeted oncology agents have the potential to increase the risk of cardiovascular events, including prolongation of QT interval and associated cardiac arrhythmias. This study investigated the effect of adavosertib on the QTc interval in patients with advanced solid tumors.

Methods

Eligible patients were ≥ 18 years of age with advanced solid tumors for which no standard therapy existed. Patients received adavosertib 225 mg twice daily on days 1–2 at 12-h intervals and once on day 3. Patients underwent digital 12-lead electrocardiogram and pharmacokinetic assessments pre-administration and time-matched assessments during the drug administration period. The relationship between maximum plasma drug concentration (Cmax) and baseline-adjusted corrected QT interval by Fridericia (QTcF) was estimated using a prespecified linear mixed-effects model.

Results

Twenty-one patients received adavosertib. Concentration–QT modeling of ΔQTcF and the upper limit of the 90% confidence interval corresponding to the geometric mean of Cmax observed on days 1 and 3 were below the threshold for regulatory concern (not > 10 ms). No significant relationship between ΔQTcF (vs baseline) and adavosertib concentration was identified (P = 0.27). Pharmacokinetics and the adverse event (AE) profile were consistent with previous studies at this dose. Eleven (52.4%) patients experienced 17 treatment-related AEs in total, including diarrhea and nausea (both reported in six [28.6%] patients), vomiting (reported in two [9.5%] patients), anemia, decreased appetite, and constipation (all reported in one [4.8%] patient).

Conclusion

Adavosertib does not have a clinically important effect on QTc prolongation.

ClinicalTrials.gov

NCT03333824.
Grundlagen der Nierenpathologie für Pathologen – Teil 2
Authors: Gaspert Ariana , Büttner-Herold Maike , Amann Kerstin
Published: June 2023

Die Nierenbiopsiediagnostik bei medizinisch indizierten Biopsien und Nierentransplantatbiopsien wird überwiegend in Zentren mit ausgebildeten Nephropathologen betrieben. Veränderungen im nichtneoplastischen Nierenparenchym bei tumorbedingten Nephrektomien, insbesondere nichtentzündliche, ischämisch und vaskulär bedingte Veränderungen oder diabetische Nephropathie, können bei Patienten mit lokalisiertem Nierenkarzinomen und gutem tumorassoziiertem Überleben prognostisch von größerer Bedeutung sein als das Tumorleiden an sich. In diesem Teil zu den Grundlagen der Nierenpathologie für Pathologen sollen die häufigsten nichtentzündlichen Nierenerkrankungen im vaskulären, glomerulären und tubulointerstitiellen Kompartiment beleuchtet werden.
Assessment of antibody levels to SARS-CoV-2 in patients with idiopathic inflammatory myopathies receiving treatment with intravenous immunoglobulin
Authors: Bae Sangmee Sharon , Faure-Kumar Emmanuelle , Ferbas Kathie , Wang Jennifer , Shahbazian Ani , Truong Linh , Yang Howard , McMahon Maureen , FitzGerald John D. , Charles-Schoeman Christina
Published: June 2023

Antibodies to Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) have been reported in pooled healthy donor plasma and intravenous immunoglobulin products (IVIG). It is not known whether administration of IVIG increases circulating anti-SARS-CoV-2 antibodies (COVID ab) in IVIG recipients. COVID ab against the receptor binding domain of the spike protein were analyzed using a chemiluminescent microparticle immunoassay in patients with idiopathic inflammatory myopathies (IIM) both receiving and not receiving IVIG (IVIG and non-IVIG group, respectively). No significant differences in COVID ab levels were noted between IVIG and non-IVIG groups (417 [67–1342] AU/mL in IVIG vs 5086 [43–40,442] AU/mL in non-IVIG, p = 0.11). In linear regression models including all post-vaccination patient samples, higher number of vaccine doses was strongly associated with higher COVID ab levels (2.85 [1.21, 4.48] log AU/mL, regression coefficient $$\beta$$
β
[95% CI], p = 0.001), while use of RTX was associated with lower ab levels (2.73 [− 4.53, − 0.93] log AU/mL, $$\beta$$
β
[95%CI], p = 0.004). In the IVIG group, higher total monthly doses of IVIG were associated with slightly higher COVID ab levels (0.02 [0.002–0.05] log AU/mL, p = 0.04). While patients on IVIG did not have higher COVID ab levels compared to the non-IVIG group, higher monthly doses of IVIG were associated with higher circulating levels of COVID ab in patients receiving IVIG, particularly in patients concomitantly receiving RTX. Our findings suggest that IIM patients, especially those at increased risk of COVID infection and worse COVID outcomes due to RTX therapy may have protective benefits when on concurrent IVIG treatment.
MRI proton density fat fraction for estimation of tumor grade in steatotic hepatocellular carcinoma
Authors: Kupczyk Patrick Arthur , Kurt Darius , Endler Christoph , Luetkens Julian Alexander , Kukuk Guido Matthias , Fronhoffs Florian , Fischer Hans-Peter , Attenberger Ulrike Irmgard , Pieper Claus Christian
Published: June 2023

Objectives

Image-based detection of intralesional fat in focal liver lesions has been established in diagnostic guidelines as a feature indicative of hepatocellular carcinoma (HCC) and associated with a favorable prognosis. Given recent advances in MRI-based fat quantification techniques, we investigated a possible relationship between intralesional fat content and histologic tumor grade in steatotic HCCs.

Methods

Patients with histopathologically confirmed HCC and prior MRI with proton density fat fraction (PDFF) mapping were retrospectively identified. Intralesional fat of HCCs was assessed using an ROI-based analysis and the median fat fraction of steatotic HCCs was compared between tumor grades G1-3 with non-parametric testing. ROC analysis was performed in case of statistically significant differences (p < 0.05). Subgroup analyses were conducted for patients with/without liver steatosis and with/without liver cirrhosis.

Results

A total of 57 patients with steatotic HCCs (62 lesions) were eligible for analysis. The median fat fraction was significantly higher for G1 lesions (median [interquartile range], 7.9% [6.0─10.7%]) than for G2 (4.4% [3.2─6.6%]; p = .001) and G3 lesions (4.7% [2.8─7.8%]; p = .036). PDFF was a good discriminator between G1 and G2/3 lesions (AUC .81; cut-off 5.8%, sensitivity 83%, specificity 68%) with comparable results in patients with liver cirrhosis. In patients with liver steatosis, intralesional fat content was higher than in the overall sample, with PDFF performing better in distinguishing between G1 and G2/3 lesions (AUC .92; cut-off 8.8%, sensitivity 83%, specificity 91%).

Conclusions

Quantification of intralesional fat using MRI PDFF mapping allows distinction between well- and less-differentiated steatotic HCCs.

Clinical relevance

PDFF mapping may help optimize precision medicine as a tool for tumor grade assessment in steatotic HCCs. Further investigation of intratumoral fat content as a potential prognostic indicator of treatment response is encouraged.

Key Points

• MRI proton density fat fraction mapping enables distinction between well- (G1) and less- (G2 and G3) differentiated steatotic hepatocellular carcinomas.

• In a retrospective single-center study with 62 histologically proven steatotic hepatocellular carcinomas, G1 tumors showed a higher intralesional fat content than G2 and G3 tumors (7.9% vs. 4.4% and 4.7%; p = .004).

• In liver steatosis, MRI proton density fat fraction mapping was an even better discriminator between G1 and G2/G3 steatotic hepatocellular carcinomas.
Development and validation of dynamic bioenergetic model for intermittent ergometer cycling
Authors: Lidar Julius , Ainegren Mats , Sundström David
Published: June 2023

Purpose

The aim of this study was to develop and validate a bioenergetic model describing the dynamic behavior of the alactic, lactic, and aerobic metabolic energy supply systems as well as different sources of the total metabolic energy demand.

Methods

The bioenergetic supply model consisted of terms for the alactic, lactic, and aerobic system metabolic rates while the demand model consisted of terms for the corresponding metabolic rates of principal cycling work, pulmonary ventilation, and accumulated metabolites. The bioenergetic model was formulated as a system of differential equations and model parameters were estimated by a non-linear grey-box approach, utilizing power output and aerobic metabolic rate (MRae) data from fourteen cyclists performing an experimental trial (P2) on a cycle ergometer. Validity was assessed by comparing model simulation and measurements on a similar follow-up experimental trial (P3).

Results

The root mean square error between modelled and measured MRae was 61.9 ± 7.9 W and 79.2 ± 30.5 W for P2 and P3, respectively. The corresponding mean absolute percentage error was 8.6 ± 1.5% and 10.6 ± 3.3% for P2 and P3, respectively.

Conclusion

The validation of the model showed excellent overall agreement between measured and modeled MRae during intermittent cycling by well-trained male cyclist. However, the standard deviation was 38.5% of the average root mean square error for P3, indicating not as good reliability.
Round-robin testing for LMO2 and MYC as immunohistochemical markers to screen MYC rearrangements in aggressive large B-cell lymphoma
Authors: Papaleo Natalia , Climent Fina , Tapia Gustavo , Luizaga Luis , Azcarate Juan , Bosch-Schips Jan , Muñoz-Marmol Ana M. , Salido Marta , Lome-Maldonado Carmen , Vazquez Ivonne , Colomo Luis
Published: June 2023

Aggressive large B-cell lymphomas (aLBCL) include a heterogeneous group of lymphomas with diverse biological features. One of the approaches to the diagnosis of aLBCL is based on the identification of MYC rearrangements (MYC-R), in addition to BCL2 and BCL6 rearrangements by genetic techniques, mainly fluorescent in situ hybridization (FISH). Because of the low incidence of MYC-R, the identification of useful immunohistochemistry markers to select cases for MYC FISH testing may be useful in daily practice. In a previous work, we identified a strong association between the profile CD10 positive/LMO2 negative expression and the presence of MYC-R in aLBCL and obtained good intralaboratory reproducibility. In this study, we wanted to evaluate external reproducibility. To evaluate whether LMO2 can be a reproducible marker between observers 50 aLBCL cases were circulated among 7 hematopathologists of 5 hospitals. Fleiss’ kappa index for LMO2 and MYC were 0.87 and 0.70, respectively, indicating high agreement between observers. In addition, during 2021–2022, the enrolled centers included LMO2 in their diagnostic panels to evaluate prospectively the utility of the marker, and 213 cases were analyzed. Comparing LMO2 with MYC, the group of CD10 positive cases showed higher specificity (86% vs 79%), positive predictive value (66% vs 58%), likelihood positive value (5.47 vs 3.78), and accuracy (83% vs 79%), whereas the negative predictive values remained similar (90% vs 91%). These findings place LMO2 as a useful and reproducible marker to screen MYC-R in aLBCL.
The long weight: association between distressed communities index and long-term weight outcomes following bariatric surgery
Authors: Johns Alexandra J. , Luce M. Siobhan , Kaneski Mason J. , Lowery Ryan A. , Jachniewicz Barbara , Salas Angela , McCreary Randi , Russell Raquel M. , Lyo Victoria , Ali Mohammed R. , Ahmed Shushmita M.
Published: June 2023

Background

Socioeconomic status (SES) is multifactorial, and its effect on post-bariatric weight recurrence is unclear. Distressed Community Index (DCI) is a composite SES score measuring community economic well-being. This study aims to evaluate the effect of DCI on long-term post-bariatric weight outcomes.

Methods

Retrospective analysis of patients undergoing primary laparoscopic Roux-en-Y gastric bypass or sleeve gastrectomy between 2015 and 2020 was performed. All weights in the electronic medical record (EMR), including non-bariatric visits, were captured. Patients were stratified into low tier (LT) and high tier (HT) DCI groups.

Results

Of 583 patients, 431 (73.9%) were HT and 152 (26.1%) were LT. Average bariatric follow up was 1.78 ± 1.6 years and average postoperative weight in the EMR was 3.96 ± 2.26 years. Rates of bariatric follow up within the last year were similar (13.8% LT vs 16.2% HT, p = 0.47). LT had higher percent total body weight loss (%TWL; 26% LT vs 23% HT, p < 0.01) and percent excess weight loss (%EWL; 62% vs 57%, p = 0.04) at 1 year on univariate analysis. On multivariate linear regression adjusting for baseline characteristics and surgery type, there were no differences in %EWL between groups at 1 year (p = 0.22), ≥ 3 years (p = 0.53) or ≥ 5 years (p = 0.34) postop. While on univariate analysis LT only trended towards greater percentage of patients with > 15% increase from their 1-year weight (33.3% LT vs 21.0% HT, p = 0.06), on multivariate analysis this difference was significant (OR 2.0, LT 95%CI 1.41–2.84). There were no differences in the percentage of patients with > 15% decrease in %EWL from 1 to 3 + years postop between groups (OR 0.98, LT 95% CI 0.72–1.35).

Conclusions

While low tier patients had similar weight loss at 1 year, they were twice as likely to have weight recurrence at ≥ 3 years. Further studies are needed to identify factors contributing to greater weight recurrence among this population.
Phase II clinical trial to study the safety and efficacy of combined S-1 + oxaliplatin therapy as neoadjuvant chemotherapy for locally advanced gastric cancer in older patients
Authors: Ota Mitsuhiko , Saeki Hiroshi , Uehara Hideo , Matsuda Yoshiko , Tsutsumi Satoshi , Kusumoto Tetsuya , Yasui Hisateru , Ubukata Yasunari , Yamaguchi Shohei , Orita Hiroyuki , Izawa Naoki , Kakizoe Saburo , Shimokawa Mototsugu , Yoshizumi Tomoharu , Kakeji Yoshihiro , Mori Masaki , Oki Eiji
Published: June 2023

Background

Gastrectomy with D2 dissection and adjuvant chemotherapy is the standard treatment for locally advanced gastric cancer (LAGC) in Asia. However, administering chemotherapy with sufficient intensity after gastrectomy is challenging. Several trials demonstrated the efficacy of neoadjuvant chemotherapy (NAC). However, limited studies explored the feasibility of NAC-SOX for older patients with LAGC. This phase II study (KSCC1801) evaluated the safety and efficacy of NAC-SOX in patients with LAGC aged ≥ 70 years.

Methods

Patients received three cycles of SOX130 (oxaliplatin 130 mg/m2 on day 1, oral S-1 40–60 mg twice daily for two weeks every three weeks) as NAC, followed by gastrectomy with lymph node dissection. The primary endpoint was the dose intensity (DI). The secondary endpoints were safety, R0 resection rate, pathological response rate (pRR), overall survival, and relapse-free survival.

Results

The median age of 26 enrolled patients was 74.5 years. The median DI in NAC-SOX130 was 97.2% for S-1 and 98.3% for oxaliplatin. Three cycles of NAC were administered in 25 patients (96.2%), of whom 24 (92.3%) underwent gastrectomy with lymphadenectomy. The R0 resection rate was 92.3% and the pRR (≥ grade 1b) was 62.5%. The major adverse events (≥ grade 3) were neutropenia (20.0%), thrombocytopenia (11.5%), anorexia (11.5%), nausea (7.7%), and hyponatremia (7.7%). Postoperative complications of abdominal infection, elevated blood amylase, and bacteremia occurred in one patient each. Severe diarrhea and dehydration caused one treatment-related death.

Conclusions

NAC-SOX130 is a feasible therapy for older patients, although systemic management and careful monitoring of adverse events are necessary.
The policy is always greener: impact heterogeneity of Covid-19 vaccination lotteries in the US.
Authors: Grossi Giulio
Published: June 2023

Covid-19 vaccination has posed crucial challenges to policymakers and health administrations worldwide. Besides the pressure posed by the pandemic, government administrations have to strive against vaccine hesitancy, which seems to be higher with respect to previous vaccination rollouts. To increase the vaccinated population, Ohio announced a monetary incentive as a lottery for those who were vaccinated. 18 other states followed this first example, with varying results. In this paper, we want to evaluate the effect of such policies within the potential outcome framework using the penalized synthetic control method. In the context of staggered treatment adoption, we estimate the effects at a disaggregated level using a panel dataset. We focused on policy outcomes at the county, state, and supra-state levels, highlighting differences between counties with different social characteristics and time frames for policy introduction. We also studied the treatment effect to see whether the impact of these monetary incentives was permanent or only temporary, accelerating the vaccination of citizens who would have been vaccinated in any case.