bluuebunny/crossref_metadata_2025 huggingface dataset:
Profile of the multicenter cohort of the German Cancer Consortium’s Clinical Communication Platform
Authors: Maier Daniel , Vehreschild Jörg Janne , Uhl Barbara , Meyer Sandra , Berger-Thürmel Karin , Boerries Melanie , Braren Rickmer , Grünwald Viktor , Hadaschik Boris , Palm Stefan , Singer Susanne , Stuschke Martin , Juárez David , Delpy Pierre , Lambarki Mohamed , Hummel Michael , Engels Cäcilia , Andreas Stefanie , Gökbuget Nicola , Ihrig Kristina , Burock Susen , Keune Dietmar , Eggert Angelika , Keilholz Ulrich , Schulz Hagen , Büttner Daniel , Löck Steffen , Krause Mechthild , Esins Mirko , Ressing Frank , Schuler Martin , Brandts Christian , Brucker Daniel P. , Husmann Gabriele , Oellerich Thomas , Metzger Patrick , Voigt Frederik , Illert Anna L. , Theobald Matthias , Kindler Thomas , Sudhof Ursula , Reckmann Achim , Schwinghammer Felix , Nasseh Daniel , Weichert Wilko , von Bergwelt-Baildon Michael , Bitzer Michael , Malek Nisar , Öner Öznur , Schulze-Osthoff Klaus , Bartels Stefan , Haier Jörg , Ammann Raimund , Schmidt Anja Franziska , Guenther Bernd , Janning Melanie , Kasper Bernd , Loges Sonja , Stilgenbauer Stephan , Kuhn Peter , Tausch Eugen , Runow Silvana , Kerscher Alexander , Neumann Michael , Breu Martin , Lablans Martin , Serve Hubert
Published: April 2023

Treatment concepts in oncology are becoming increasingly personalized and diverse. Successively, changes in standards of care mandate continuous monitoring of patient pathways and clinical outcomes based on large, representative real-world data. The German Cancer Consortium’s (DKTK) Clinical Communication Platform (CCP) provides such opportunity. Connecting fourteen university hospital-based cancer centers, the CCP relies on a federated IT-infrastructure sourcing data from facility-based cancer registry units and biobanks. Federated analyses resulted in a cohort of 600,915 patients, out of which 232,991 were incident since 2013 and for which a comprehensive documentation is available. Next to demographic data (i.e., age at diagnosis: 2.0% 0–20 years, 8.3% 21–40 years, 30.9% 41–60 years, 50.1% 61–80 years, 8.8% 81+ years; and gender: 45.2% female, 54.7% male, 0.1% other) and diagnoses (five most frequent tumor origins: 22,523 prostate, 18,409 breast, 15,575 lung, 13,964 skin/malignant melanoma, 9005 brain), the cohort dataset contains information about therapeutic interventions and response assessments and is connected to 287,883 liquid and tissue biosamples. Focusing on diagnoses and therapy-sequences, showcase analyses of diagnosis-specific sub-cohorts (pancreas, larynx, kidney, thyroid gland) demonstrate the analytical opportunities offered by the cohort’s data. Due to its data granularity and size, the cohort is a potential catalyst for translational cancer research. It provides rapid access to comprehensive patient groups and may improve the understanding of the clinical course of various (even rare) malignancies. Therefore, the cohort may serve as a decisions-making tool for clinical trial design and contributes to the evaluation of scientific findings under real-world conditions.
Taylorism on steroids or enabling autonomy? A systematic review of algorithmic management
Authors: Noponen Niilo , Feshchenko Polina , Auvinen Tommi , Luoma-aho Vilma , Abrahamsson Pekka
Published: April 2023

The use of algorithmic management systems is rapidly changing organizational models and practices, as millions of workers in multiple sectors worldwide are managed by computer software. Despite receiving increasing academic interest, little summarizing literature exist on the ways algorithmic systems are used in management. This article aims to fill this gap by systematically reviewing and qualitatively analyzing 172 articles on the topic. Our research contributes to the existent algorithmic management literature in three ways. First, we provide a descriptive overview of algorithmic management as a field of research. Second, we identify and synthesize the discussion on the key concepts of the topic, namely how algorithmic management: (1) simultaneously restrains and enables workers’ autonomy—yet income dependency and other factors force inflexible work practices; (2) creates a complex, digital version of Taylorism; and (3) creates new and changes existing organizational power structures. Third, as our main theoretical contribution, we create the framework of Algorithmic Management Grid that demonstrates the ways in which organizations use algorithmic systems in management. The Algorithmic Management Grid illustrates how, in both novel and traditional organizational models, algorithmic management may be used with emphasis either on controlling or enabling workers. Based on the reviewed literature, we claim that so far, companies have mostly utilized algorithmic systems in a controlling manner, neglecting the technology’s enabling potential in organizing.
Purinergic Tuning of the Tripartite Neuromuscular Synapse
Authors: Sousa-Soares Carlos , Noronha-Matos José Bernardo , Correia-de-Sá Paulo
Published: April 2023

The vertebrate neuromuscular junction (NMJ) is a specialised chemical synapse involved in the transmission of bioelectric signals between a motor neuron and a skeletal muscle fiber, leading to muscle contraction. Typically, the NMJ is a tripartite synapse comprising (a) a presynaptic region represented by the motor nerve ending, (b) a postsynaptic skeletal motor endplate area, and (c) perisynaptic Schwann cells (PSCs) that shield the motor nerve terminal. Increasing evidence points towards the role of PSCs in the maintenance and control of neuromuscular integrity, transmission, and plasticity. Acetylcholine (ACh) is the main neurotransmitter at the vertebrate skeletal NMJ, and its role is fine-tuned by co-released purinergic neuromodulators, like adenosine 5′-triphosphate (ATP) and its metabolite adenosine (ADO). Adenine nucleotides modulate transmitter release and expression of postsynaptic ACh receptors at motor synapses via the activation of P2Y and P2X receptors. Endogenously generated ADO modulates ACh release by acting via co-localised inhibitory A1 and facilitatory A2A receptors on motor nerve terminals, whose tonic activation depends on the neuronal firing pattern and their interplay with cholinergic receptors and neuropeptides. Thus, the concerted action of adenine nucleotides, ADO, and ACh/neuropeptide co-transmitters is paramount to adapting the neuromuscular transmission to the working load under pathological conditions, like Myasthenia gravis. Unravelling these functional complexities prompted us to review our knowledge about the way purines orchestrate neuromuscular transmission and plasticity in light of the tripartite synapse concept, emphasising the often-forgotten role of PSCs in this context.
Physiology-guided PCI versus CABG for left main coronary artery disease: insights from the DEFINE-LM registry
Authors: Warisawa Takayuki , Cook Christopher M. , Kawase Yoshiaki , Howard James P. , Ahmad Yousif , Seligman Henry , Rajkumar Christopher , Toya Takumi , Doi Shunichi , Nakajima Akihiro , Tanigaki Toru , Omori Hiroyuki , Nakayama Masafumi , Vera-Urquiza Rafael , Yuasa Sonoka , Sato Takao , Kikuta Yuetsu , Nishina Hidetaka , Al-Lamee Rasha , Sen Sayan , Lerman Amir , Akashi Yoshihiro J. , Escaned Javier , Matsuo Hitoshi , Davies Justin E.
Published: April 2023

There have been no studies comparing clinical outcomes of physiology-guided revascularization in patients with unprotected left main coronary disease (ULMD) between percutaneous coronary intervention (PCI) vs. coronary artery bypass grafting (CABG). The aim of this study was to assess the long-term clinical outcomes between PCI and CABG of patients with physiologically significant ULMD. From an international multicenter registry of ULMD patients interrogated with instantaneous wave-free ratio (iFR), we analyzed data from 151 patients (85 PCI vs. 66 CABG) who underwent revascularization according to the cutoff value of iFR ≤ 0.89. Propensity score matching was employed to adjust for baseline clinical characteristics. The primary endpoint was a composite of all-cause death, non-fatal myocardial infarction, and ischemia-driven target lesion revascularization. The secondary endpoints were the individual components of the primary endpoint. Mean age was 66.6 (± 9.2) years, 79.2% male. Mean SYNTAX score was 22.6 (± 8.4) and median iFR was 0.83 (IQR 0.74–0.87). After performing propensity score matching analysis, 48 patients treated with CABG were matched to those who underwent PCI. At a median follow-up period of 2.8 years, the primary endpoint occurred in 8.3% in PCI group and 20.8% in CABG group, respectively (HR 3.80; 95% CI 1.04–13.9; p = 0.043). There was no difference in each component of the primary event (p > 0.05 for all). Within the present study, iFR-guided PCI was associated with lower cardiovascular events rate in patients with ULMD and intermediate SYNTAX score, as compared to CABG.

Graphical abstract

State-of-the-art PCI vs. CABG for ULMD. Study design and primary endpoint in patients with physiologically significant ULMD. MACE was defined as the composite of all-cause death, non-fatal myocardial infarction, and target lesion revascularization. The blue line denotes the PCI arm, and the red line denotes the CABG arm. PCI was associated with significantly lower risk of MACE than CABG. CABG: coronary artery bypass grafting; iFR: instantaneous wave-free ratio; MACE: major adverse cardiovascular events; PCI: percutaneous coronary intervention; ULMD: unprotected left main coronary artery disease.
Small extracellular vesicles promote invadopodia activity in glioblastoma cells in a therapy-dependent manner
Authors: Whitehead Clarissa A. , Fang Haoyun , Su Huaqi , Morokoff Andrew P. , Kaye Andrew H. , Hanssen Eric , Nowell Cameron J. , Drummond Katharine J. , Greening David W. , Vella Laura J. , Mantamadiotis Theo , Stylli Stanley S.
Published: April 2023

Purpose

The therapeutic efficacy of radiotherapy/temozolomide treatment for glioblastoma (GBM) is limited by the augmented invasiveness mediated by invadopodia activity of surviving GBM cells. As yet, however the underlying mechanisms remain poorly understood. Due to their ability to transport oncogenic material between cells, small extracellular vesicles (sEVs) have emerged as key mediators of tumour progression. We hypothesize that the sustained growth and invasion of cancer cells depends on bidirectional sEV-mediated cell–cell communication.

Methods

Invadopodia assays and zymography gels were used to examine the invadopodia activity capacity of GBM cells. Differential ultracentrifugation was utilized to isolate sEVs from conditioned medium and proteomic analyses were conducted on both GBM cell lines and their sEVs to determine the cargo present within the sEVs. In addition, the impact of radiotherapy and temozolomide treatment of GBM cells was studied.

Results

We found that GBM cells form active invadopodia and secrete sEVs containing the matrix metalloproteinase MMP-2. Subsequent proteomic studies revealed the presence of an invadopodia-related protein sEV cargo and that sEVs from highly invadopodia active GBM cells (LN229) increase invadopodia activity in sEV recipient GBM cells. We also found that GBM cells displayed increases in invadopodia activity and sEV secretion post radiation/temozolomide treatment. Together, these data reveal a relationship between invadopodia and sEV composition/secretion/uptake in promoting the invasiveness of GBM cells.

Conclusions

Our data indicate that sEVs secreted by GBM cells can facilitate tumour invasion by promoting invadopodia activity in recipient cells, which may be enhanced by treatment with radio-chemotherapy. The transfer of pro-invasive cargos may yield important insights into the functional capacity of sEVs in invadopodia.
A Systematic Review of Individual Tree Crown Detection and Delineation with Convolutional Neural Networks (CNN)
Authors: Zhao Haotian , Morgenroth Justin , Pearse Grant , Schindler Jan
Published: April 2023

Purpose of Review

Crown detection and measurement at the individual tree level provide detailed information for accurate forest management. To efficiently acquire such information, approaches to conduct individual tree detection and crown delineation (ITDCD) using remotely sensed data have been proposed. In recent years, deep learning, specifically convolutional neural networks (CNN), has shown potential in this field. This article provides a systematic review of the studies that used CNN for ITDCD and identifies major trends and research gaps across six perspectives: accuracy assessment methods, data types, platforms and resolutions, forest environments, CNN models, and training strategies and techniques.

Recent Findings

CNN models were mostly applied to high-resolution red–green–blue (RGB) images. When compared with other state-of-the-art approaches, CNN models showed significant improvements in accuracy. One study reported an increase in detection accuracy of over 11%, while two studies reported increases in F1-score of over 16%. However, model performance varied across different forest environments and data types. Several factors including data scarcity, model selection, and training approaches affected ITDCD results.

Future studies could (1) explore data fusion approaches to take advantage of the characteristics of different types of remote sensing data, (2) further improve data efficiency with customised sample approaches and synthetic samples, (3) explore the potential of smaller CNN models and compare their learning efficiency with commonly used models, and (4) evaluate impacts of pre-training and parameter tunings.
Hospital antibiotic consumption—an interrupted time series analysis of the early and late phases of the COVID-19 pandemic in Poland, a retrospective study
Authors: Siewierska Małgorzata , Gajda Mateusz , Opalska Aleksandra , Brudło Michał , Krzyściak Paweł , Gryglewska Barbara , Różańska Anna , Wójkowska-Mach Jadwiga
Published: April 2023

Background

COVID-19 has been challenging for the entire healthcare system, due to the lack of sufficient treatment protocols, especially during initial phases and as regards antibiotic use. The aim of this study was to identify the trends of antimicrobial consumption in one of the largest tertiary hospitals in Poland during COVID-19.

Methods

This is a retrospective study conducted at the University Hospital in Krakow, Poland, between Feb/Mar 2020 and Feb 2021. It included 250 patients. All included patients were hospitalized due to COVID-19 with confirmed SARS-CoV-2 infection without bacterial co-infections during the first phase of COVID-19 in Europe and following 3-month intervals: five equal groups of patients in each. COVID severity and antibiotic consumption were assessed according to WHO recommendations.

Results

In total 178 (71.2%) patients received antibiotics with a incidence rate of laboratory-confirmed healthcare-associated infection (LC-HAI) was 20%. The severity of COVID-19 was mild in 40.8%, moderate in 36.8%, and severe in 22.4% cases. The ABX administration was significantly higher for intensive care unit (ICU) patients (97.7% vs. 65.7%). Length of hospital stay was extended for patients with ABX (22.3 vs. 14.4 days). In total, 3 946.87 DDDs of ABXs were used, including 1512.63 DDDs in ICU, accounting for 780.94 and 2522.73 per 1000 hospital days, respectively. The median values of antibiotic DDD were greater among patients with severe COVID-19 than others (20.92). Patients admitted at the beginning of the pandemic (Feb/Mar, May 2020) had significantly greater values of median DDDs, respectively, 25.3 and 16.0 compared to those admitted in later (Aug, Nov 2020; Feb 2021), respectively, 11.0, 11.0 and 11.2, but the proportion of patients receiving ABX therapy was lower in Feb/Mar and May 2020 (62.0 and 48.0%), whereas the highest during the late period of the pandemic, i.e., in Aug, Nov. 2020 and Feb. 2021 (78% and both 84.0%).

Conclusions

Data suggest great misuse of antibiotics without relevant data about HAIs. Almost all ICU patients received some antibiotics, which was correlated with prolonged hospitalization.
Three-dimensional sedimentation patterns of two interacting disks in a viscous fluid
Authors: Liu Yi , Guo Yu , Yang Bo , Pan Dingyi , Xia Zhenhua , Yu Zhaosheng , Wang Lian-Ping
Published: April 2023

The sedimentation of two spherical solid objects in a viscous fluid has been extensively investigated and well understood. However, a pair of flat disks (in three dimensions) settling in the fluid shows more complex hydrodynamic behaviour. The present work aims to improve the understanding of this phenomenon by performing direct numerical simulation and physical experiments. The present results show that the sedimentation processes are significantly influenced by disk shape, characterized by a dimensionless moment of inertia I*, and Reynolds number Re of the leading disk. For the flatter disks with smaller I*, steady falling with enduring contact transits to periodic swinging with intermittent contacts as Re increases. The disks with larger I* tend to fall in a drafting-kissing-tumbling mode at low Re and to remain separated at high Re. Based on I* and Re, a phase diagram is created to classify the two-disk falling into ten distinctive patterns. The planar motion or three-dimensional motion of the disks is determined primarily by Re. Turbulent disturbance flows at a high Re contribute to the chaotic three-dimensional rotation of the disks. The chance for the two disks to contact is increased when I* and Re are reduced.
Penetrative convection: heat transport with marginal stability assumption
Authors: Ding Zijing , Ouyang Zhen
Published: April 2023

This paper investigates heat transport in penetrative convection with a marginally stable temporal-horizontal-averaged field or background field. Assuming that the background field is steady and is stabilised by the nonlinear perturbation terms, we obtain an eigenvalue problem with an unknown background temperature

$\tau$

by truncating the nonlinear terms. Using a piecewise profile for

$\tau$

, we derived an analytical scaling law for heat transport in penetrative convection as

$Ra\rightarrow \infty$

:

$Nu=(1/8)(1-T_M)^{5/3}Ra^{1/3}$

(

$Nu$

is the Nusselt number;

$Ra$

is the Rayleigh number and

$T_M$

corresponds to the temperature at which the density is maximal). A conditional lower bound on

$Nu$

, under the marginal stability assumption, is then derived from a variational problem. All the solutions to the full system should deliver a higher heat flux than the lower bound if they satisfy the marginal stability assumption. However, data from the present direct numerical simulations and previous optimal steady solutions by Ding & Wu (J. Fluid Mech., vol. 920, 2021, A48) exhibit smaller

$Nu$

than the lower bound at large

$Ra$

, indicating that these averaged fields are over-stabilised by the nonlinear terms. To incorporate a more physically plausible constraint to bound heat transport, an alternative approach, i.e. the quasilinear approach is invoked which delivers the highest heat transport and agrees well with Veronis's assumption, i.e.

$Nu\sim Ra^{1/3}$

(Astrophys. J., vol. 137, 1963, p. 641). Interestingly, the background temperature

$\tau$

yielded by the quasilinear approach can be non-unique when instability is subcritical.
The Southern-sky MWA Rapid Two-metre (SMART) pulsar survey—I. Survey design and processing pipeline
Authors: Bhat N. D. R. , Swainston N. A. , McSweeney S. J. , Xue M. , Meyers B.W. , Kudale S. , Dai S. , Tremblay S. E. , van Straten W. , Shannon R. M. , Smith K. R. , Sokolowski M. , Ord S. M. , Sleap G. , Williams A. , Hancock P. J. , Lange R. , Tocknell J. , Johnston-Hollitt M. , Kaplan D. L. , Tingay S. J. , Walker M.
Published: April 2023

We present an overview of the Southern-sky MWA Rapid Two-metre (SMART) pulsar survey that exploits the Murchison Widefield Array’s large field of view and voltage-capture system to survey the sky south of 30$^{\circ}$in declination for pulsars and fast transients in the 140–170 MHz band. The survey is enabled by the advent of the Phase II MWA’s compact configuration, which offers an enormous efficiency in beam-forming and processing costs, thereby making an all-sky survey of this magnitude tractable with the MWA. Even with the long dwell times employed for the survey (4800 s), data collection can be completed in$<$100 h of telescope time, while still retaining the ability to reach a limiting sensitivity of$\sim$2–3 mJy (at 150 MHz, near zenith), which is effectively 3–5 times deeper than the previous-generation low-frequency southern-sky pulsar survey, completed in the 1990s. Each observation is processed to generate$\sim$5000–8000 tied-array beams that tessellate the full$\sim 610\, {\textrm{deg}^{2}}$field of view (at 155 MHz), which are then processed to search for pulsars. The voltage-capture recording of the survey also allows a multitude ofpost hocprocessing options including the reprocessing of data for higher time resolution and even exploring image-based techniques for pulsar candidate identification. Due to the substantial computational cost in pulsar searches at low frequencies, the survey data processing is undertaken in multiple passes: in the first pass, a shallow survey is performed, where 10 min of each observation is processed, reaching about one-third of the full-search sensitivity. Here we present the system overview including details of ongoing processing and initial results. Further details including first pulsar discoveries and a census of low-frequency detections are presented in a companion paper. Future plans include deeper searches to reach the full sensitivity and acceleration searches to target binary and millisecond pulsars. Our simulation analysis forecasts$\sim$300 new pulsars upon the completion of full processing. The SMART survey will also generate a complete digital record of the low-frequency sky, which will serve as a valuable reference for future pulsar searches planned with the low-frequency Square Kilometre Array.
Antiviral treatment in schizophrenia: a randomized pilot PET study on the effects of valaciclovir on neuroinflammation
Authors: Jonker Iris , Doorduin Janine , Knegtering Henderikus , van't Hag Erna , Dierckx Rudi A. , de Vries Erik F. J. , Schoevers Robert A. , Klein Hans C.
Published: April 2023

Background

Patients with schizophrenia experience cognitive impairment, which could be related to neuroinflammation in the hippocampus. The cause for such hippocampal inflammation is still unknown, but it has been suggested that herpes virus infection is involved. This study therefore aimed to determine whether add-on treatment of schizophrenic patients with the anti- viral drug valaciclovir would reduce hippocampal neuroinflammation and consequently improve cognitive symptoms.

Methods

We performed a double-blind monocenter study in 24 male and female patients with schizophrenia, experiencing active psychotic symptoms. Patients were orally treated with the anti-viral drug valaciclovir for seven consecutive days (8 g/day). Neuroinflammation was measured with Positron Emission Tomography using the translocator protein ligand [11C]-PK11195, pre-treatment and at seven days post-treatment, as were psychotic symptoms and cognition.

Results

Valaciclovir treatment resulted in reduced TSPO binding (39%) in the hippocampus, as well as in the brainstem, frontal lobe, temporal lobe, parahippocampal gyrus, amygdala, parietal lobe, occipital lobe, insula and cingulate gyri, nucleus accumbens and thalamus (31–40%) when using binding potential (BPND) as an outcome. With total distribution volume (VT) as outcome we found essentially the same results, but associations only approached statistical significance (p = 0.050 for hippocampus). Placebo treatment did not affect neuroinflammation. No effects of valaciclovir on psychotic symptoms or cognitive functioning were found.

Conclusion

We found a decreased TSPO binding following antiviral treatment, which could suggest a viral underpinning of neuroinflammation in psychotic patients. Whether this reduced neuroinflammation by treatment with valaciclovir has clinical implications and is specific for schizophrenia warrants further research.
Efficacy of dynamic interpersonal therapy for major depressive disorder in China: results of a multicentered, three-arm, randomized, controlled trial
Authors: Wang Yuan , Yao Jiayu , Koszycki Diana , Jiang Wenhui , Fang Fang , Wang Minghong , Tao Jing , Zhao Wenqing , Liu Yilan , Su Shanshan , Peng Yihua , Wang Hongyan , Wang Lanlan , Gao Rui , Gu Junjie , Zhang Jie , Bai Yanle , Wu Yanru , Su Yousong , Zhao Yating , Zheng Ziwei , Chen Shuangyi , Qiu Jianyin
Published: April 2023

Background

Dynamic interpersonal therapy (DIT) is a brief, structured psychodynamic psychotherapy with demonstrated efficacy in treating major depressive disorder (MDD). The aim of the study was to determine whether DIT is an acceptable and efficacious treatment for MDD patients in China.

Method

Patients were randomized to 16-week treatments with either DIT plus antidepressant medication (DIT + ADM; n = 66), general supportive therapy plus antidepressant medication (GST + ADM; n = 75) or antidepressant medication alone (ADM; n = 70). The Hamilton Depression Rating Scale (HAMD) administered by blind raters was the primary efficacy measure. Assessments were completed during the acute 16-week treatment and up to 12-month posttreatment.

Results

The group × time interaction was significant for the primary outcome HAMD (F = 2.900, df1 = 10, df2 = 774.72, p = 0.001) in the acute treatment phase. Pairwise comparisons showed a benefit of DIT + ADM over ADM at weeks 12 [least-squares (LS) mean difference = −3.161, p = 0.007] and 16 (LS mean difference = −3.237, p = 0.004). Because of the unexpected high attrition during the posttreatment follow-up phase, analyses of follow-up data were considered exploratory. Differences between DIT + ADM and ADM remained significant at the 1-, 6-, and 12-month follow-up (ps range from 0.001 to 0.027). DIT + ADM had no advantage over GST + ADM during the acute treatment phase. However, at the 12-month follow-up, patients who received DIT remained less depressed.

Conclusions

Acute treatment with DIT or GST in combination with ADM was similarly efficacious in reducing depressive symptoms and yielded a better outcome than ADM alone. DIT may provide MDD patients with long-term benefits in symptom improvement but results must be viewed with caution.
Paucity problems and some relatives of Vinogradov’s mean value theorem
Authors: WOOLEY TREVOR D.
Published: April 2023

When$k\geqslant 4$and$0\leqslant d\leqslant (k-2)/4$, we consider the system of Diophantine equations\begin{align*}x_1^j+\ldots +x_k^j=y_1^j+\ldots +y_k^j\quad (1\leqslant j\leqslant k,\, j\ne k-d).\end{align*}We show that in this cousin of a Vinogradov system, there is a paucity of non-diagonal positive integral solutions. Our quantitative estimates are particularly sharp when$d=o\!\left(k^{1/4}\right)$.
Activism and Objectivity in Political Research
Authors: Frazer Michael L.
Published: April 2023

There are two opposed views on the proper relationship between academic research and political activism. The first argues that academics who study politics must remain objective, hence precluding activism. The second argues that academics can and should also be political activists, hence precluding scholarly objectivity. This article argues against an assumption shared by these otherwise opposing positions: that activism and objectivity are incompatible. It conceptually identifies and then normatively defends a form of objectivity characterized by active engagement with evidence that is what Max Weber calls “inconvenient” for one’s existing beliefs and commitments. Far from being incompatible with political activism, this form of objectivity is essential to its success. Since scholars, activists, and scholar-activists alike would all benefit from active engagement with inconvenient evidence, I conclude that academic institutions should promote this form of objectivity among both activist and non-activist scholars, while political organizations should promote the same virtue among both academic and non-academic activists.
A broadband Butler-based dual-polarized omni-directional antenna
Authors: Wu Xiaoqing , Shen Lin-Ping , Zhang Lijun
Published: April 2023

This paper presents a broadband Butler-based slant ±45° dual-polarized omni-directional antenna working at the frequency band of 1.69–2.69 GHz for extending wireless communication network capacity in the limited service size. The proposed antenna realizes a 360° full coverage with wider bandwidth in a compact cylinder and increases the network capacity to 6 × 6 MIMO instead of using three traditional 2 × 2 MIMO omni-directional antennas. Theoretical analysis, simulation, and fabrication are conducted to validate the idea of the proposed omni-directional antenna. The measured results show 46% bandwidth with 15 dB return loss, 2.2 dB azimuth null and 8.9–10.5 dBi gain for port-C with 0° phase increment, and 14.1 dB azimuth null and 9.6–10.6 dBi gain for port-L/R (left/right) with ±120° phase increment, respectively.
Compact modified hourglass-shaped aperture-coupled antenna for radar applications
Authors: Priyalatha P. , Kumari Runa , Nandi Sourav
Published: April 2023

This paper furnishes a compact modified hourglass-shaped aperture-coupled antenna for radar applications. The effect of slots of various shapes and various slot lengths on the input impedance, radiation pattern, and gain of the antenna are analyzed. The proposed antenna, designed using a modified hourglass-shaped aperture, offers a gain of 8.214 dBi for an compact antenna with a dimension of 20.4 × 20.4 × 1.041 mm3 and an aperture area of 2.495 mm2. Implementation of this proposed modified hourglass-shaped aperture offers a high gain per unit radiating patch area of 40.26 dB/$\lambda _g ^2$ and a high gain per unit aperture area of 1324.84 dB/$\lambda _g ^2$. The proposed aperture feeds a circular patch which radiates at its resonant frequency of 10.5 GHz. The proposed design is fabricated and the simulated results are verified experimentally. Equivalent circuit analysis is also done. A measured gain of 7.2 dBi is observed at 10.5 GHz. The physical area of the antenna is reduced without compromising the gain by judiciously choosing the shape of slot with more degree of freedom for impedance matching. The proposed antenna is well suited for the unit cell of phased array antennas for X-band missile radar applications.
Assessment of Top of Atmosphere, Atmospheric and Surface Energy Budgets in CMIP6 Models on Regional Scales
Authors: Li Donghao , Folini Doris , Wild Martin
Published: April 2023

We examine top of atmosphere (TOA), atmospheric, and surface energy budget components of 53 CMIP6 models for the period 2000–2009 on regional scales with respect to two reference data sets: the NASA Energy and Water cycle Study (NEWS), from which we adopt the regional decomposition, and the Clouds and the Earth's Radiant Energy System (CERES) Energy Balanced and Filled (EBAF). Focusing on regional scale, CMIP6 models tend to have more energy entering or less energy leaving the climate systems at TOA over the Northern Hemisphere land, Southern Hemisphere ocean and the polar regions compared to CERES EBAF, while the contrary applies in other regions. Atmospheric net shortwave and longwave fluxes both tend to be underestimated in CMIP6 models as compared to EBAF, with substantial regional differences. Regional surface radiative fluxes as reported by NEWS and EBAF can differ substantially. Nevertheless, robust regional biases exist in CMIP6. Surface upward shortwave radiation is overestimated by 43 (81%) models over Eurasia. For almost all surface radiative flux components over the North Atlantic and Indian Ocean, there are at least 21 (40%) models which fall outside the NEWS uncertainty range. Latent heat flux is overestimated over most of the land and ocean regions while firm conclusions for sensible heat flux remain elusive due to discrepancies between different reference data sets. Compared to CMIP5, there is an overall improvement in CMIP6 on regional scale. Still, substantial deficiencies and spreads on regional scale remain, which are potentially translated into an inadequate simulation of atmospheric dynamics or hydrological cycle.
Record‐Strong Eastward Propagating 4‐Day Wave in the Southern Hemisphere Observed During the 2019 Antarctic Sudden Stratospheric Warming
Authors: Luo Jiahui , Ma Zheng , Gong Yun , Zhang Shaodong , Xiao Qiao , Huang Chunming , Huang Kaiming
Published: April 2023

Based on the zonal winds from the Modern‐Era Retrospective Analysis for Research and Applications, version 2 reanalysis data, we investigate the enhancement of an eastward propagating 4‐day wave (E4DW) during the 2019 Antarctic sudden stratospheric warming (SSW). The amplitudes of E4DW are centered at 50°S and 50 km with a maximum amplitude of ∼20 m/s. The enhanced E4DW significantly exceeds the climatological level and has the strongest amplitude in the Southern Hemisphere since 1980. Our results show that the E4DW is generated by the atmospheric instabilities via a double‐jet configuration of the zonal mean zonal winds. Our analysis further indicates that the special structure of the zonal mean zonal winds caused by the 2019 Antarctic SSW at the stratopause is responsible for the excitation of the record‐strong E4DW in 2019 in the Southern Hemisphere.
Characterizing the Variability of Boundary Currents and Ocean Heat Content Around New Zealand Using a Multi‐Decadal High‐Resolution Regional Ocean Model
Authors: Kerry Colette , Roughan Moninya , De Souza Joao
Published: April 2023

New Zealand is located in the southwest Pacific Ocean and is surrounded by a complex system of boundary currents that vary on a variety of time scales, with important impacts on weather, primary productivity, and fisheries. While various observational and modeling studies have shed light on many of the characteristics of New Zealand's ocean circulation, this study provides a comprehensive, quantitative, seamless, 3‐dimensional characterization of the region's boundary current circulation and ocean heat content. We use a 28 yr long hydrodynamic model simulation that accurately represents the mean and variability of the ocean circulation to characterize and quantify the temporal and spatial variability across the region. We show that low‐frequency variability in boundary current transport and upper ocean heat content are correlated over the entire New Zealand oceanic region. Oceanic eddies dominate heat content variability at intra‐annual scales in the northeast of the region, while on the west and southeast coasts heat content varies predominantly at interannual scales controlled by large‐scale changes in the subtropical and sub‐Antarctic fronts. The model shows a significant downstream strengthening and deepening of the boundary currents off northeast New Zealand which, if confirmed by observations, could suggest a significant new understanding of this Western Boundary Current system. This study presents a region‐wide characterization of the temporal and spatial variability of ocean currents and heat content, and their interconnections, providing a vital basis for understanding climate change impacts and the increasing occurrence of marine heatwaves.
Using naltrexone to validate a human laboratory test system to screen new medications for alcoholism (TESMA)- a randomized clinical trial
Authors: Spreer Maik , Grählert Xina , Klut Ina-Maria , Al Hamdan Feras , Sommer Wolfgang H. , Plawecki Martin H. , O’Connor Sean , Böttcher Michael , Sauer Cathrin , Smolka Michael N. , Zimmermann Ulrich S.
Published: April 2023

This registered clinical trial sought to validate a laboratory test system devised to screen medications for alcoholism treatment (TESMA) under different contingencies of alcohol reinforcement. Forty-six nondependent, but at least medium-risk drinkers were given the opportunity to earn intravenous infusions of ethanol, or saline, as rewards for work in a progressive-ratio paradigm. Work demand pattern and alcohol exposure dynamics were devised to achieve a gradual shift from low-demand work for alcohol (WFA) permitting quickly increasing breath alcohol concentrations (BrAC) to high-demand WFA, which could only decelerate an inevitable decrease of the previously earned BrAC. Thereby, the reward contingency changed, modeling different drinking motivations. The experiment was repeated after at least 7 days of randomized, double-blinded treatment with naltrexone, escalated to 50 mg/d, or placebo. Subjects treated with naltrexone reduced their cumulative WFA (cWFA) slightly more than participants receiving placebo. This difference was not statistically significant in the preplanned analysis of the entire 150 min of self-administration, i.e., our primary endpoint (p = 0.471, Cohen’s d = 0.215). Naltrexone serum levels correlated with change in cWFA (r = −0.53; p = 0.014). Separate exploratory analyses revealed that naltrexone significantly reduced WFA during the first, but not the second half of the experiment (Cohen’s d = 0.643 and 0.14, respectively). Phase-dependent associations of WFA with changes in subjective stimulation, wellbeing and desire for alcohol suggested that the predominant reinforcement of WFA was positive during the first phase only, and might have been negative during the second. We conclude that the TESMA is a safe and practical method. It bears the potential to quickly and efficiently screen new drugs for their efficacy to attenuate positively reinforced alcohol consumption. It possibly also provides a condition of negative reinforcement, and for the first time provides experimental evidence suggesting that naltrexone’s effect might depend on reward contingency.
GPR84 regulates pulmonary inflammation by modulating neutrophil functions
Authors: Wang Si-wei , Zhang Qing , Lu Dan , Fang You-chen , Yan Xiao-ci , Chen Jing , Xia Zhi-kan , Yuan Qian-ting , Chen Lin-hai , Zhang Yang-ming , Nan Fa-jun , Xie Xin
Published: April 2023

Acute lung injury (ALI) is an acute, progressive hypoxic respiratory failure that could develop into acute respiratory distress syndrome (ARDS) with very high mortality rate. ALI is believed to be caused by uncontrolled inflammation, and multiple types of immune cells, especially neutrophils, are critically involved in the development of ALI. The treatment for ALI/ARDS is very limited, a better understanding of the pathogenesis and new therapies are urgently needed. Here we discover that GPR84, a medium chain fatty acid receptor, plays critical roles in ALI development by regulating neutrophil functions. GPR84 is highly upregulated in the cells isolated from the bronchoalveolar lavage fluid of LPS-induced ALI mice. GPR84 deficiency or blockage significantly ameliorated ALI mice lung inflammation by reducing neutrophils infiltration and oxidative stress. Further studies reveal that activation of GPR84 strongly induced reactive oxygen species production from neutrophils by stimulating Lyn, AKT and ERK1/2 activation and the assembly of the NADPH oxidase. These results reveal an important role of GPR84 in neutrophil functions and lung inflammation and strongly suggest that GPR84 is a potential drug target for ALI.
Prognostic value of early bone marrow MRD status in CAR-T therapy for myeloma
Authors: Bansal Radhika , Baksh Mizba , Larsen Jeremy T. , Hathcock Matthew A. , Dingli David , Stewart A. Keith , Kapoor Prashant , Kourelis Taxiarchis , Hayman Suzanne R. , Warsame Rahma M. , Fonseca Rafael , Bergsagel P. Leif , Ailawadhi Sikander , Kumar Shaji K. , Lin Yi
Published: April 2023

Bone marrow (BM) assessment of minimal residual disease (MRD) is prognostic for survival in multiple myeloma (MM). BM is still hypocellular at month 1 post CAR-T, thus the value of MRD negative (MRDneg) status at this timepoint is unclear. We examined the impact of month 1 BM MRD status in MM patients who received CART at Mayo Clinic between 8/2016 and 6/2021. Among 60 patients, 78% were BM-MRDneg at month 1; and 85% (40/47) of these patients also had decreased to less than normal level of both involved and uninvolved free light chain (FLC < NL). Patients who achieved CR/sCR had higher rates of month 1 BM-MRDneg and FLC < NL. The rate of sustained BM-MRDneg was 40% (19/47). Rate of conversion from MRDpos to MRDneg was 5%(1/20). At month 1, 38%(18/47) of the BM-MRDneg were hypocellular. Recovery to normal cellularity was observed in 50%(7/14) with a median time to normalization at 12 months (range: 3–Not reached). Compared to Month 1 BM-MRDpos patients, patients who were BM-MRDneg had longer PFS irrespective of BM cellularity [PFS: 2.9 months (95% CI, 1.2-NR) vs. 17.5 months (95% CI, 10.4-NR), p < 0.0001]. Month 1 BM-MRDneg and FLC below normal were associated with prolonged survival. Our data support the continued evaluation of BM early post-CART infusion as a prognostic tool.
Effectiveness of mRNA COVID-19 vaccine booster doses against Omicron severe outcomes
Authors: Grewal Ramandip , Nguyen Lena , Buchan Sarah A. , Wilson Sarah E. , Nasreen Sharifa , Austin Peter C. , Brown Kevin A. , Fell Deshayne B. , Gubbay Jonathan B. , Schwartz Kevin L. , Tadrous Mina , Wilson Kumanan , Kwong Jeffrey C.
Published: April 2023

We estimated the effectiveness of booster doses of monovalent mRNA COVID-19 vaccines against Omicron-associated severe outcomes among adults in Ontario, Canada. We used a test-negative design to estimate vaccine effectiveness (VE) against hospitalization or death among SARS-CoV-2-tested adults aged ≥50 years from January 2 to October 1, 2022, stratified by age and time since vaccination. We also compared VE during BA.1/BA.2 and BA.4/BA.5 sublineage predominance. We included 11,160 cases and 62,880 tests for test-negative controls. Depending on the age group, compared to unvaccinated adults, VE was 91–98% 7–59 days after a third dose, waned to 76–87% after ≥240 days, was restored to 92–97% 7–59 days after a fourth dose, and waned to 86–89% after ≥120 days. VE was lower and declined faster during BA.4/BA.5 versus BA.1/BA.2 predominance, particularly after ≥120 days. Here we show that booster doses of monovalent mRNA COVID-19 vaccines restored strong protection against severe outcomes for at least 3 months after vaccination. Across the entire study period, protection declined slightly over time, but waned more during BA.4/BA.5 predominance.
OTTERS: a powerful TWAS framework leveraging summary-level reference data
Authors: Dai Qile , Zhou Geyu , Zhao Hongyu , Võsa Urmo , Franke Lude , Battle Alexis , Teumer Alexander , Lehtimäki Terho , Raitakari Olli T. , Esko Tõnu ,   eQTLGen Consortium, Agbessi Mawussé , Ahsan Habibul , Alves Isabel , Andiappan Anand Kumar , Arindrarto Wibowo , Awadalla Philip , Battle Alexis , Beutner Frank , Jan Bonder Marc , Boomsma Dorret I. , Christiansen Mark W. , Claringbould Annique , Deelen Patrick , Favé Marie-Julie , Frayling Timothy , Gharib Sina A. , Gibson Greg , Heijmans Bastiaan T. , Hemani Gibran , Jansen Rick , Kähönen Mika , Kalnapenkis Anette , Kasela Silva , Kettunen Johannes , Kim Yungil , Kirsten Holger , Kovacs Peter , Krohn Knut , Kronberg Jaanika , Kukushkina Viktorija , Kutalik Zoltan , Lee Bernett , Loeffler Markus , Marigorta Urko M. , Mei Hailang , Milani Lili , Montgomery Grant W. , Müller-Nurasyid Martina , Nauck Matthias , Nivard Michel G. , Penninx Brenda , Perola Markus , Pervjakova Natalia , Pierce Brandon L. , Powell Joseph , Prokisch Holger , Psaty Bruce M. , Ripatti Samuli , Rotzschke Olaf , Rüeger Sina , Saha Ashis , Scholz Markus , Schramm Katharina , Seppälä Ilkka , Slagboom Eline P. , Stehouwer Coen D. A. , Stumvoll Michael , Sullivan Patrick , ‘t Hoen Peter A. C. , Thiery Joachim , Tong Lin , Tönjes Anke , van Dongen Jenny , van Iterson Maarten , van Meurs Joyce , Veldink Jan H. , Verlouw Joost , Visscher Peter M. , Völker Uwe , Westra Harm-Jan , Wijmenga Cisca , Yaghootka Hanieh , Yang Jian , Zeng Biao , Zhang Futao , Epstein Michael P. , Yang Jingjing
Published: April 2023

Most existing TWAS tools require individual-level eQTL reference data and thus are not applicable to summary-level reference eQTL datasets. The development of TWAS methods that can harness summary-level reference data is valuable to enable TWAS in broader settings and enhance power due to increased reference sample size. Thus, we develop a TWAS framework called OTTERS (Omnibus Transcriptome Test using Expression Reference Summary data) that adapts multiple polygenic risk score (PRS) methods to estimate eQTL weights from summary-level eQTL reference data and conducts an omnibus TWAS. We show that OTTERS is a practical and powerful TWAS tool by both simulations and application studies.
Electrochemical generation of hydrogen peroxide from a zinc gallium oxide anode with dual active sites
Authors: Li Lejing , Hu Zhuofeng , Kang Yongqiang , Cao Shiyu , Xu Liangpang , Yu Luo , Zhang Lizhi , Yu Jimmy C.
Published: April 2023

Electrochemical water oxidation enables the conversion of H2O to H2O2. It holds distinct advantages to the O2 reduction reaction, which is restricted by the inefficient mass transfer and limited solubility of O2 in aqueous media. Nonetheless, most reported anodes suffer from high overpotentials (usually >1000 mV) and low selectivity. Electrolysis at high overpotentials often causes serious decomposition of peroxides and leads to declined selectivity. Herein, we report a ZnGa2O4 anode with dual active sites to improve the selectivity and resist the decomposition of peroxides. Its faradaic efficiency reaches 82% at 2.3 V versus RHE for H2O2 generation through both direct (via OH−) and indirect (via HCO3−) pathways. The percarbonate is the critical species generated through the conversion of bicarbonate at Ga-Ga dual sites. The peroxy bond is stable on the surface of the ZnGa2O4 anode, significantly improving faradaic efficiency.
Regulating electronic states of nitride/hydroxide to accelerate kinetics for oxygen evolution at large current density
Authors: Zhai Panlong , Wang Chen , Zhao Yuanyuan , Zhang Yanxue , Gao Junfeng , Sun Licheng , Hou Jungang
Published: April 2023

Rational design efficient transition metal-based electrocatalysts for oxygen evolution reaction (OER) is critical for water splitting. However, industrial water-alkali electrolysis requires large current densities at low overpotentials, always limited by intrinsic activity. Herein, we report hierarchical bimetal nitride/hydroxide (NiMoN/NiFe LDH) array as model catalyst, regulating the electronic states and tracking the relationship of structure-activity. As-activated NiMoN/NiFe LDH exhibits the industrially required current density of 1000 mA cm−2at overpotential of 266 mV with 250 h stability for OER. Especially, in-situ electrochemical spectroscopic reveals that heterointerface facilitates dynamic structure evolution to optimize electronic structure. Operando electrochemical impedance spectroscopy implies accelerated OER kinetics and intermediate evolution due to fast charge transport. The OER mechanism is revealed by the combination of theoretical and experimental studies, indicating as-activated NiMoN/NiFe LDH follows lattice oxygen oxidation mechanism with accelerated kinetics. This work paves an avenue to develop efficient catalysts for industrial water electrolysis via tuning electronic states.