bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized phase 2 umbrella study of various neoadjuvant therapies for patients with muscle-invasive urothelial carcinoma of the bladder (MIBC) who are cisplatin-ineligible or refuse cisplatin therapy and undergoing radical cystectomy (Optimus).
Authors: Necchi Andrea , Zakharia Yousef , Ghali Nadeem , Smith Michael , Hamer-Maansson J. E. , Lindley Anouk , Loriot Yohann , Meeks Joshua J 
Published: February 2022

TPS599 Background: A growing body of data support that the key to generating anti-tumor immune responses triggered by administration of immuno-oncology (IO) agents, is the activation and invasion of T lymphocytes. Checkpoint inhibitors (CPIs) are being actively explored in the neoadjuvant setting of MIBC. CPIs documented 30-40% pathologic complete response-rates (ypT0N0) in previous trials. Increasingly, novel IO agents are being developed in combinations with anti PD(L)-1 therapies. Understanding the changes in the tumor microenvironment that occur with the addition of novel immunomodulating agents to PD(L)-1 inhibitors can help inform whether a compound is viable for further development. The OPTIMUS trial is a window of opportunity, neoadjuvant platform design study in MIBC patients that are cisplatin-ineligible. The study investigates the addition of the indoleamine 2, 3-dioxygenase 1 (IDO1) inhibitor epacadostat to the PD-1 inhibitor retifanlimab. The platform design allows for investigation of other novel immune-modulating combinations. Methods: This is an open-label, randomized, Phase 2, multi-treatment group, window-of-opportunity, platform study for participants with MIBC undergoing radical cystectomy who refuse or are not eligible for cisplatin-based neoadjuvant chemotherapy (NCT04586244). Participants are randomized based on tumor tissue PD-L1 CPS ≥ 10 or PD-L1 CPS < 10 to one of the following treatment groups: Treatment Group A (epacadostat + retifanlimab); Treatment Group B (retifanlimab monotherapy); Treatment Group C (epacadostat monotherapy). 18 patients will be enrolled in each of Treatment Groups A and B. 9 patients will be enrolled into Treatment Group C. Total treatment duration is a maximum of 10 weeks. The platform study design allows for addition of future treatment groups. Pre-treatment biopsy is obtained through transurethral resection of bladder tumor (TURBT), followed by neoadjuvant treatment, followed by radical cystectomy. In all treatment groups, tissue from the surgical specimen(s) is collected and compared with the initial pre-treatment samples. The primary endpoint is the change from baseline in CD8+ lymphocytes within resected tumor. Secondary endpoints include safety and tolerability, rates of ypT0N0 response, and major pathologic response. Exploratory analyses include tumoral changes in gene cell expression profile, immune-cell protein and metabolic marker levels, and spatial relationships between cell types. Plasma is also collected and will be investigated for changes in cytokines and other inflammatory or metabolic markers. Clinical trial information: NCT04586244.
Rugotaxis: Droplet motion without external energy supply
Authors: Theodorakis Panagiotis E. , Egorov Sergei A. , Milchev Andrey 
Published: February 2022

Abstract
Nano-patterned substrates offer possibilities for controlling the motion of fluids without external energy supply in novel technologies in microfluidics, coatings, etc. Here, we report on the rugotaxial motion of droplets on wrinkled substrates with gradient in the wavelength of the wrinkles by exploring a broad range of parameters, such as amplitude of the wrinkles, substrate wettability, droplet size and wavelength gradient. Adopting a theoretical and molecular dynamics approach, we determine the Cassie-Baxter and Wenzel states of the droplets, investigate the efficiency of rugotaxis as a function of different parameters, and discuss additional effects, such as pinning. We find that shallow wrinkles characterised by small wavelength gradients, and moderate adhesion of the droplet to the substrate favour the rugotaxis motion with growing droplet size, when pinning is avoided. We also find that the driving force in rugotaxis is the gain in interfacial energy between the droplet and the substrate as the droplet enters regions of denser wrinkles (smaller wavelengths of the wrinkles).
Adipose Mitochondrial Complex I Deficiency Modulates Inflammation and Glucose Homeostasis in a Sex-Dependent Manner
Authors: Choi Kyung-Mi , Ryan Karen K , Yoon John C 
Published: February 2022

AbstractMitochondrial dysfunction in adipose tissue has been associated with type 2 diabetes, but it is unclear whether it is a cause or the consequence. Mitochondrial complex I is a major site of reactive oxygen species generation and a therapeutic target. Here we report that genetic deletion of the complex I subunit Ndufs4 specifically in adipose tissue results in an increased propensity to develop diet-induced weight gain, glucose intolerance, and elevated levels of fat inflammatory genes. This outcome is apparent in young males but not in young females, suggesting that females are relatively protected from the adverse consequences of adipose mitochondrial dysfunction for metabolic health. Mutant mice of both sexes exhibit defects in brown adipose tissue thermogenesis. Fibroblast growth factor 21 (FGF21) signaling in adipose tissue is selectively blunted in male mutant mice relative to wild-type littermates, consistent with sex-dependent regulation of its autocrine/paracrine action in adipocytes. Together, these findings support that adipocyte-specific mitochondrial dysfunction is sufficient to induce tissue inflammation and can cause systemic glucose abnormalities in male mice.
The Prediction Model Using Thyroid-stimulating Immunoglobulin Bioassay For Relapse of Graves’ Disease
Authors: Baek Han-Sang , Lee Jaejun , Jeong Chai-Ho , Lee Jeongmin , Ha Jeonghoon , Jo Kwanhoon , Kim Min-Hee , Cho Jae Hyoung , Kang Moo Il , Lim Dong-Jun 
Published: February 2022

Abstract

Objective
Thyroid-stimulating immunoglobulin (TSI) bioassay has a better ability to predict the relapse rate of Graves’ disease (GD) than the thyroid-stimulating hormone (TSH)-binding inhibitory immunoglobulin method in terms of measuring the TSH receptor antibody. However, the optimal TSI bioassay cutoff for predicting relapse after antithyroid drug (ATD) withdrawal is not well evaluated.

Methods
This retrospective study enrolled GD patients who had been treated with ATD and obtained their TSI bioassay &lt;140% from January 2010 to December 2019 in a referral hospital.

Results
Among 219 study subjects, 86 patients (39.3%) experienced relapse. The TSI bioassay value of 66.5% significantly predicted the relapse of GD (P = 0.049). The group with a TSI bioassay value &gt; 66.5% were expected to show a 23.8% relapse rate at 2 from ATD withdrawal, and the group with a TSI &lt; 66.5% had a 12.7% relapse rate based on Kaplan-Meier curves analysis. The TSI bioassay showed a good ability to predict relapse GD in the female group (P = 0.041) but did not in the male group (P = 0.573). The risk scoring based on the nomogram with risk factors for GD relapse, which was constructed to overcome the limitation, increased the predictive ability of GD relapse by 11.5% compared to the use of the TSI bioassay alone.

Conclusions
The cutoff value of the TSI bioassay to predict GD relapse should be lower than that for diagnosing GD. However, as the single use of the TSI bioassay has limitations, a nomogram with multiple risk factors including TSI bioassay could be helpful to predict GD relapse.
The Association Between Angiotensin II and Renin Kinetics in Patients After Cardiac Surgery
Authors: Meersch Melanie , Weiss Raphael , Massoth Christina , Küllmar Mira , Saadat-Gilani Khaschayar , Busen Manuel , Chawla Lakhmir , Landoni Giovanni , Bellomo Rinaldo , Gerss Joachim , Zarbock Alexander 
Published: February 2022

BACKGROUND:
Hyperreninemia after cardiac surgery is associated with cardiovascular instability. Angiotensin II (AT-II) could potentially attenuate hyperreninemia while maintaining target blood pressure. This study assesses the association between AT-II usage and renin levels in cardiac surgery patients with postoperative hyperreninemia and vasoplegia.

METHODS:
Between September 2020 and March 2021, we retrospectively identified 40 cardiac surgery patients with high Δ-renin levels (4 hours after cardiopulmonary bypass [CPB] minus preoperative levels) (defined as higher than 3.7 µU/mL) and vasopressor use who received a vasopressor therapy with either AT-II or continued norepinephrine alone. The primary outcome was the renin plasma level at 12 hours after surgery, adjusted by the renin plasma level at 4 hours after surgery.

RESULTS:
Overall, the median renin plasma concentration increased from a baseline with median of 44.3 µU/mL (Q1–Q3, 14.6–155.5) to 188.6 µU/mL (Q1–Q3, 29.8–379.0) 4 hours after CPB. High Δ-renin (difference between postoperation and preoperation) patients (higher than 3.7 µU/mL) were then treated with norepinephrine alone (median dose of 3.25 mg [Q1–Q3, 1.00–4.75]) or with additional AT-II (norepinephrine dose: 1.33 mg [Q1–Q3, 0.78–2.04]; AT-II dose: 0.34 mg [Q1–Q3, 0.29–0.78]). At 12 hours after surgery, AT-II patients had lower renin levels than standard of care patients (71.7 µU/mL [Q1–Q3, 21.9–211.4] vs 130.6 µU/mL [Q1–Q3, 62.9–317.0]; P = .034 adjusting for the renin plasma level at 4 hours after surgery).

CONCLUSIONS:
In cardiac surgery patients with hypotonia and postoperative high Δ-renin levels, AT-II was associated with reduced renin plasma levels for at 12 hours and significantly decreased norepinephrine use, while norepinephrine alone was associated with increased renin levels. Further studies of AT-II in cardiac surgery appear justified.
Synthesis and Reactivity of Heterobimetallic Co-PAlP Pincer Complexes
Authors: Semba Kazuhiko , Shimoura Fumiya , Nakao Yoshiaki 
Published: February 2022

Abstract
A cobalt complex ligated with a PAlP pincer ligand was synthesized. The Lewis acidity of the aluminum atom on the cobalt complex was confirmed by coordination with 4-dimethylaminopyridine (DMAP). Reactions of the cobalt complex with H2O, EtOH, i-PrOH, and t-BuOH efficiently afforded the corresponding cobalt hydride complexes.
Biphasic split-bolus injection protocol for routine contrast-enhanced chest CT: comparison with conventional early-phase single bolus technique
Authors: Kul Melahat , Kuru Öz Diğdem , Gürsoy Coruh Ayşegül , Özalp Ateş Funda , Gülpınar Başak , Uzun Çağlar , Atasoy K.Çetin 
Published: February 2022

Objectives:
To present a routine contrast-enhanced chest CT protocol with a split-bolus injection technique achieving combined early- and delayed phase images with a single aquisition, and to compare this technique with a conventional early-phase single-bolus chest CT protocol we formerly used at our institution, in terms of attenuation of great thoracic vessels, pleura, included hepatic and portal venous enhancement, contrast-related artifacts, and image quality.

Methods:
A total of 202 patients, who underwent routine contrast-enhanced chest CT examination aquired with either conventional early-phase single-bolus technique (group A,n = 102) or biphasic split-bolus protocol (group B,n = 100), were retrospectively included. Attenuation measurements were made by two radiologists independently on mediastinal window settings using a circular ROI at the following sites: main pulmonary artery (PA) at its bifurcation level, thoracal aorta (TA) at the level of MPA bifurcation,portal vein (PV) at porta hepatis, left and right hepatic lobe, and if present, thickened pleura (&gt;2 mm) at the level with the most intense enhancement. Respective normalized enhancement values were also calculated. Contrast-related artifacts were graded and qualitative evaluation of mediastinal lymph nodes was performed by both reviewers independently. Background noise was measured and contrast-to-noise ratios (CNRs) of the liver and TA were calculated.

Results:
While enhancement of thoracic vessels and normalised MPA enhancement did not differ significantly between both groups (p &gt; 0.05), enhancement and normalised enhancement of pleura, liver parenchyma and PV was significantly greater in group B (p &lt; 0.001). Perivenous artifacts limiting evaluation were less frequent in group B than in A and mediastinal lymph nodes were judged to be evaluated worse in group A than in group B with an excellent agreement between both observers. No significant difference was detected in CNRTA (p = 0.633), whereas CNR liver was higher in group B (p &lt; 0.001).

Conclusion:
Our split-bolus chest CT injection protocol enables simultaneous enhancement for both vascular structures and soft tissues, and thus, might raise diagnostic confidence without the need of multiple acquisitions.

Advances in knowledge:
We think that this CT protocol might also be a promising alternative in lung cancer staging, where combined contrast-enhanced CT of the chest and abdomen is indicated. We therefore suggest to further evaluate its diagnostic utility in this setting, in particular in comparison with a late delayed chest-upper abdominal CT imaging protocol.
Digital twins for well-being: an overview
Authors: Ferdousi Rahatara , Laamarti Fedwa , Hossain M. Anwar , Yang Chunsheng , El Saddik Abdulmotaleb 
Published: February 2022

Digital twin (DT) has gained success in various industries, and it is now getting attention in the healthcare industry in the form of well-being digital twin (WDT). In this paper, we present an overview of WDT to understand its potential scope, architecture and impact. We then discuss the definition and the benefits of WDT. After that, we present the evolution of DT frameworks. Subsequently we discuss the challenges, the different types, the drawbacks, and potential application areas of WDT. Finally we present the requirements for a WDT framework extracted from the literature.
Treatment profiles and trajectories surrounding the diagnosis of major depressive disorder: a research protocol for a Danish register-based study.
Authors: Herold Jeberg Pernille , Overgaard Nielsen Anne Marije Christina , Osler Merete , Kim Wirum-Andersen Marie , Jacobsen Ramune , Almarsdóttir Anna Birna , Jarlov Jensen Kristoffer , Petersen Janne 
Published: February 2022

Background: Major depressive disorder (MDD) is a prevalent illness that causes significant suffering and expenses at the personal and societal levels. The disorder is subject to heterogeneity reflected by diverse clinical phenotypes and assorted responses to treatment. Research on MDD treatments have focused on one treatment at a time, however many patients receive several different treatments. Considering the number of available treatment options, we hypothesize that it is possible to identify clinically meaningful groups of patients based on their psychiatric treatment. The objective of this study is therefore to identify psychiatric treatment profiles and trajectories of patients with major depressive disorder and, for the identified profiles and trajectories, to assess clinical and sociodemographic factors. Method: The study will be a population-based register study of patients with major depressive disorder in the Danish National Patient Register between 2011 and 2015. Using latent class analyses, we will identify homogenous groups of patients based on their psychiatric treatment patterns. These patterns constitute psychiatric treatment profiles which will be identified at six time-intervals, from 1.5 years before to 3 years after diagnosis of major depressive disorder. By cross-tabulating the identified treatment profiles, we will establish psychiatric treatment trajectories. Patients sharing profiles and trajectories will be characterized. Discussion: Identification of psychiatric treatment profiles and trajectories based on an unsupervised learning algorithm have the potential to reveal hidden patterns of psychiatric treatment. This will potentially pave the way for future studies of treatment combinations and a larger insight into the different courses of treatment. Furthermore, the assessment of clinical and sociodemographic factors may indicate different patient characteristics across treatment profiles and trajectories.
A protocol for a longitudinal, observational cohort study of infection and exposure to zoonotic and vector-borne diseases across a land-use gradient in Sabah, Malaysian Borneo: a socio-ecological systems approach
Authors: Fornace Kimberly , Manin Benny Obrain , Matthiopoulos Jason , Ferguson Heather M. , Drakeley Chris , Ahmed Kamruddin , Khoon Koay Teng , Ewers Robert M. , Daim Sylvia , Chua Tock Hing 
Published: February 2022

Introduction.Landscape changes disrupt environmental, social and biological systems, altering pathogen spillover and transmission risks. This study aims to quantify the impact of specific land management practices on spillover and transmission rates of zoonotic and vector-borne diseases within Malaysian Borneo. This protocol describes a cohort study with integrated ecological sampling to assess how deforestation and agricultural practices impact pathogen flow from wildlife and vector populations to human infection and detection by health facilities. This will focus on malaria, dengue and emerging arboviruses (Chikungunya and Zika), vector-borne diseases with varying contributions of simian reservoirs within this setting.Methods.A prospective longitudinal observational cohort study will be established in communities residing or working within the vicinity of the Stability of Altered Forest Ecosystems (SAFE) Project, a landscape gradient within Malaysian Borneo encompassing different plantation and forest types. The primary outcome of this study will be transmission intensity of selected zoonotic and vector-borne diseases, as quantified by changes in pathogen-specific antibody levels. Exposure will be measured using paired population-based serological surveys conducted at the beginning and end of the two-year cohort study. Secondary outcomes will include the distribution and infection rates ofAedesandAnophelesmosquito vectors, human risk behaviours and clinical cases reported to health facilities. Longitudinal data on human behaviour, contact with wildlife and GPS tracking of mobility patterns will be collected throughout the study period. This will be integrated with entomological surveillance to monitor densities and pathogen infection rates ofAedesandAnophelesmosquitoes relative to land cover. Within surrounding health clinics, continuous health facility surveillance will be used to monitor reported infections and febrile illnesses. Models will be developed to assess spillover and transmission rates relative to specific land management practices and evaluate abilities of surveillance systems to capture these risks.
Abnormal optical response of PAMAM dendrimer-based silver nanocomposite metamaterials
Authors: Wu Xianfeng , Li Zhenchun , Zhao Yuan , Yang Chaoshun , Zhao Wei , Zhao Xiaopeng 
Published: February 2022

Optical metamaterials present opportunities and challenges for manipulation of light. However, metamaterials with visible and near infrared responses are still particularly challenging to fabricate due to the complex preparation process and high loss. Here, a visible light poly(amidoamine) (PAMAM)-Ag metamaterial is prepared with the assistance of fifth-generation PAMAM (5G PAMAM), based on the dendritic structure. The large area of metamaterials, where Ag nanoparticles are spherical with diameters of

∼
9

nm

and distributed in a multilevel netlike sphere, results in broadband resonance. The negative Goos–Hänchen shift and anomalous spin Hall effect of light generated by 5G PAMAM-Ag in visible broadband are observed, and a strong slab focusing effect at 750–1050 nm is demonstrated. In addition, the simulation shows possible application of the dendritic structure in topological photonics. The results offer advances in the preparation of large-scale visible light metamaterials, showing the potential for subwavelength super-resolution imaging and quantum optical information fields.
Secondary attack rates in primary and secondary school bubbles following a confirmed case: Active, prospective national surveillance, November to December 2020, England
Authors: Powell Annabel A. , Ireland Georgina , Baawuah Frances , Beckmann Joanne , Okike Ifeanyichukwu O. , Ahmad Shazaad , Garstang Joanna , Brent Andrew J. , Brent Bernadette , Aiano Felicity , Hargreaves James , Langan Sinéad M. , Mangtani Punam , Nguipdop-Djomo Patrick , Sturgess Joanna , Oswald William , Halliday Katherine , Rourke Emma , Dawe Fiona , Amin-Chowdhury Zahin , Kall Meaghan , Zambon Maria , Poh John , Ijaz Samreen , Lackenby Angie , Elli Joanna , Brown Kevin E. , Diamond Sir Ian , Ramsay Mary E. , Ladhani Shamez N. 
Published: February 2022

Background
Following the full re-opening of schools in England and emergence of the SARS-CoV-2 Alpha variant, we investigated the risk of SARS-CoV-2 infection in students and staff who were contacts of a confirmed case in a school bubble (school groupings with limited interactions), along with their household members.

Methods
Primary and secondary school bubbles were recruited into sKIDsBUBBLE after being sent home to self-isolate following a confirmed case of COVID-19 in the bubble. Bubble participants and their household members were sent home-testing kits comprising nasal swabs for RT-PCR testing and whole genome sequencing, and oral fluid swabs for SARS-CoV-2 antibodies.

Results
During November-December 2020, 14 bubbles were recruited from 7 schools, including 269 bubble contacts (248 students, 21 staff) and 823 household contacts (524 adults, 299 children). The secondary attack rate was 10.0% (6/60) in primary and 3.9% (4/102) in secondary school students, compared to 6.3% (1/16) and 0% (0/1) among staff, respectively. The incidence rate for household contacts of primary school students was 6.6% (12/183) and 3.7% (1/27) for household contacts of primary school staff. In secondary schools, this was 3.5% (11/317) and 0% (0/1), respectively. Household contacts were more likely to test positive if their bubble contact tested positive although there were new infections among household contacts of uninfected bubble contacts.

Interpretation
Compared to other institutional settings, the overall risk of secondary infection in school bubbles and their household contacts was low. Our findings are important for developing evidence-based infection prevention guidelines for educational settings.