bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regional biogeography versus intra-annual dynamics of the root and soil microbiome
Authors: Bell-Dereske Lukas P. , Benucci Gian Maria Niccolò , da Costa Pedro Beschoren , Bonito Gregory , Friesen Maren L. , Tiemann Lisa K. , Evans Sarah E. 
Published: June 2023

Abstract
Background
Root and soil microbial communities constitute the below-ground plant microbiome, are drivers of nutrient cycling, and affect plant productivity. However, our understanding of their spatiotemporal patterns is confounded by exogenous factors that covary spatially, such as changes in host plant species, climate, and edaphic factors. These spatiotemporal patterns likely differ across microbiome domains (bacteria and fungi) and niches (root vs. soil).

Results
To capture spatial patterns at a regional scale, we sampled the below-ground microbiome of switchgrass monocultures of five sites spanning > 3 degrees of latitude within the Great Lakes region. To capture temporal patterns, we sampled the below-ground microbiome across the growing season within a single site. We compared the strength of spatiotemporal factors to nitrogen addition determining the major drivers in our perennial cropping system. All microbial communities were most strongly structured by sampling site, though collection date also had strong effects; in contrast, nitrogen addition had little to no effect on communities. Though all microbial communities were found to have significant spatiotemporal patterns, sampling site and collection date better explained bacterial than fungal community structure, which appeared more defined by stochastic processes. Root communities, especially bacterial, were more temporally structured than soil communities which were more spatially structured, both across and within sampling sites. Finally, we characterized a core set of taxa in the switchgrass microbiome that persists across space and time. These core taxa represented < 6% of total species richness but > 27% of relative abundance, with potential nitrogen fixing bacteria and fungal mutualists dominating the root community and saprotrophs dominating the soil community.

Conclusions
Our results highlight the dynamic variability of plant microbiome composition and assembly across space and time, even within a single variety of a plant species. Root and soil fungal community compositions appeared spatiotemporally paired, while root and soil bacterial communities showed a temporal lag in compositional similarity suggesting active recruitment of soil bacteria into the root niche throughout the growing season. A better understanding of the drivers of these differential responses to space and time may improve our ability to predict microbial community structure and function under novel conditions.
What is the Prevalence of General Anxiety Disorder and Depression Symptoms in Semi-elite Australian Football Players: A Cross-Sectional Study
Authors: Henderson Anthony , Harris Sarah Ann , Kirkham Troy , Charlesworth Jonathon , Murphy Myles Calder 
Published: June 2023

Abstract
Background
The prevalence of anxiety and depression symptoms in semi-elite Australian footballers is unknown. The primary objective of this study was to determine the prevalence of generalised anxiety disorder (GAD) and depressive symptoms in semi-elite Australian Football players. Our secondary objective was to explore the association between demographic and football-specific factors with GAD and depressive symptoms. A cross-sectional epidemiological study including 369 semi-elite Western Australian Football League (WAFL) players from the Men and Women’s 2022 season (n = 337 men, 91%) was conducted. Symptoms of depression were measured using the Patient Health Questionnaire-9 scale (PHQ-9) and symptoms of GAD with the GAD-7 scale.

Results
Our response rate was 82.9%. Thirteen players had missing data. The prevalence of GAD symptoms was 8.5% in men and 28.6% in women (10% overall). The prevalence of depressive symptoms was 20% in men and 57% in women (23% overall). Being a woman (gender) was associated with a sevenfold increased risk of GAD and/or depression symptoms [odds ratio (OR): 7.33, 95% confidence interval (CI): 3.18–16.92; p < 0.001]. Players of ‘Aboriginal or Torres Strait Islander’ ethnicity were two times more likely to report GAD and/or depression symptoms in comparison to players of ‘Australian’ ethnicity (OR: 2.13; 95% CI: 1.01–4.49; p = 0.048). Concussion history was not a significant risk factor for GAD or depression symptoms.

Conclusion
This study demonstrated that approximately 1 in 10 WAFL players met the diagnostic cut-off criteria for probable GAD, and 1 in 5 for probable depression. The prevalence for depression symptoms in this study were far higher than the national average in the comparative age bracket. WAFL women’s players also reported a substantially higher prevalence of GAD and depressive symptoms than men, and should be further investigated as a priority by the WAFL.
Progress of tissue adhesives based on proteins and synthetic polymers
Authors: Han Gi-Yeon , Hwang Soo-Kyung , Cho Ki-Hyun , Kim Hyun-Joong , Cho Chong-Su 
Published: June 2023

Abstract
In recent years, polymer-based tissue adhesives (TAs) have been developed as an alternative to sutures to close and seal incisions or wounds owing to their ease of use, rapid application time, low cost, and minimal tissue damage. Although significant research is being conducted to develop new TAs with improved performances using different strategies, the applications of TAs are limited by several factors, such as weak adhesion strength and poor mechanical properties. Therefore, the next-generation advanced TAs with biomimetic and multifunctional properties should be developed. Herein, we review the requirements, adhesive performances, characteristics, adhesive mechanisms, applications, commercial products, and advantages and disadvantages of proteins- and synthetic polymer-based TAs. Furthermore, future perspectives in the field of TA-based research have been discussed.
Radiographic involvement of cervical facet joints in ankylosing spondylitis: a longitudinal analysis in correlation with vertebral body lesions
Authors: Lee Tae-Han , Lee Seunghun , Koo Bon San , Joo Kyung Bin , Kim Tae-Hwan 
Published: June 2023

Abstract
Background
The inability to assess structural changes in facet joints is a limitation of established radiographic scoring systems for ankylosing spondylitis (AS). We compared radiographic evidence of ankylosis in cervical facet joints and cervical vertebral bodies in patients with AS.

Methods
We analysed longitudinal data collected from 1106 AS patients and assessed 4984 spinal radiographs obtained up to 16 years of follow-up. Comparisons between cervical facet joints and cervical vertebral bodies focused on the presence of ankylosis, which was defined by at least one facet joint exhibiting complete ankylosis (according to the method of de Vlam) or at least one vertebral body with a bridging syndesmophyte (according to the modified Stoke Ankylosing Spondylitis Spinal Score [mSASSS]). Ankylosis was assessed over time using spinal radiographs collected during follow-up periods stratified in 4-year increments.

Results
Patients with cervical facet joint ankylosis had higher cervical mSASSS, sacroiliitis grades, and inflammatory markers, with more prevalent hip involvement and uveitis. Overall, the numbers of spinal radiographs indicating ankylosis were comparable between cervical facet joints (17.8%) and cervical vertebral bodies (16.8%), and they usually presented together (13.5%). We observed similar proportions of radiographs with ankylosis only in cervical facet joints (4.3%) and cervical vertebral bodies (3.3%). As damage progressed, configurations with both cervical facet joint ankylosis and bridging syndesmophytes became more predominant with longer follow-up times, while configurations with cervical facet joint ankylosis only or bridging syndesmophytes only were less frequently observed.

Conclusions
Evidence of cervical facet joint ankylosis appears as often as bridging syndesmophytes on routine AS spinal radiographs. Presence of cervical facet joint ankylosis should be considered because it may have a higher disease burden.
Four-years retention rate of golimumab administered after discontinuation of non-TNF inhibitors in patients with inflammatory rheumatic diseases
Authors: Pombo-Suárez Manuel , Seoane-Mato Daniel , Díaz-González Federico , Sánchez-Alonso Fernando , Sánchez-Jareño Marta , Cea-Calvo Luis , Castrejón Isabel 
Published: June 2023

Abstract
Background
In patients with rheumatic diseases, the use of biological (b) or targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARDs) after discontinuation of tumor necrosis factor inhibitors (TNFi) is known to be effective. However, data on the use of TNFi after discontinuation of non-TNFi bDMARDs or tsDMARDs (non-TNFi) are scarce. This study assessed the 4-years golimumab retention in patients with rheumatic diseases when used after discontinuation of non-TNFi.

Methods
Adults with rheumatoid arthritis (RA; n = 72), psoriatic arthritis (PsA; n = 30) or axial spondyloarthritis (axSpA; n = 23) who initiated golimumab after discontinuation of non-TNFi from the Spanish registry of biological drugs (BIOBADASER) were analyzed retrospectively. The retention rate (drug survival or persistence) of golimumab up to 4 years was evaluated.

Results
The golimumab retention rate was 60.7% (51.4–68.8) at year 1, 45.9% (36.0–55.2) at year 2, 39.9% (29.8–49.7) at year 3 and 33.4% (23.0–44.2) at year 4. Retention rates did not differ significantly whether golimumab was used as second, third, or fourth/subsequent line of therapy (p log-rank = 0.462). Golimumab retention rates were higher in axSpA or PsA patients than in RA patients (p log-rank = 0.002). When golimumab was administered as third or fourth/subsequent line, the 4-years retention rate after discontinuation of non-TNFi was similar to that after discontinuation of TNFi.

Conclusion
In patients who discontinued non-TNFi, most of whom received golimumab as third/subsequent line of therapy, one-third of patients remained on golimumab at year 4. Retention rates were higher in patients with axSpA and PsA than in those with RA.
Incidence of soft tissue releases in robotic assisted cementless TKA with mechanical alignment and flexion gap balancing
Authors: Selvanathan Nanchappan , Ayeni Femi E. , Sorial Rami 
Published: June 2023

Abstract
Background
To ensure the success of total knee arthroplasty (TKA), precise bone cuts and a well-balanced soft tissue envelope are crucial. Soft tissue release may be necessary, subject to various factors. Therefore, documenting the type, frequency, and necessity of soft tissue releases can establish a benchmark for comparing different alignment techniques and philosophies and evaluating their outcomes. The purpose of this study was to demonstrate that robotic-assisted knee surgery requires minimal soft tissue release.

Methods
We prospectively documented and retrospectively reviewed the soft tissue releases employed in securing ligament balance in the first 175 patients who received robotic-assisted TKAs at Nepean Hospital. ROSA was utilized in all surgeries with the aim of restoring mechanical coronal alignment, with a flexion gap balancing technique. Surgeries were performed between December 2019 to August 2021 by a single surgeon who used a standard medial parapatellar approach without a tourniquet, and the cementless persona prosthesis. All patients were followed up for a minimum of 6 months post-surgery. Soft tissue releases included any form of medial release for varus knee, posterolateral release for valgus knee and PCL fenestration or sacrifice.

Results
There were 131 female and 44 male patients, aged between 48 to 89 years (average 60 years). The preoperative HKA ranged from 22 degrees varus to 28 degrees valgus, with 71% of patients presenting with a varus deformity. For the whole group, the no need for soft tissue release was documented in 123 patients (70.3%), small fenestrated releases of PCL in 27 (15.4%), sacrifice of PCL in 8 (4.5%), medial releases in 4 (2.3%) and posterolateral releases in 13 (7.4%). In 29.7% of patients in whom a soft tissue release was necessary for balance, over half were/received minor fenestrations of the PCL. Outcomes to date included no revisions or impending revisions, 2 MUAs (1%), and Oxford knee scores averaged 40 at 6 months.

Conclusion
We concluded that Robot technology enhanced the precision of bone cuts and allowed for titration of required soft tissue releases to achieve optimal balance.
A phase 1/2, first-in-human trial of ZB131, a novel antibody targeting cancer-specific plectin (CSP) in advanced solid tumors.
Authors: Sommerhalder David , Piha-Paul Sarina A. , Pelster Meredith , Borad Mitesh J. , Vandross Andrae Lavon , Spira Alexander I. , Perez Samantha , Brinton Lindsey , Kelly Kimberly , Ramanathan Ramesh K. , Reilley Matthew 
Published: June 2023

3083 Background: Cancer-Specific Plectin (CSP) is a novel pro-tumorigenic target that is selectively expressed on the surface of tumors, while absent from benign tissue. CSP is highly expressed in many solid cancers, particularly pancreatic (PC), cholangiocarcinoma (CCA), and ovarian (OC). ZB131 (Zielbio), is a humanized anti-CSP IgG1 monoclonal antibody that binds specifically to CSP on the surface of tumor cells, rapidly internalizes and modulates key proliferative and cytoskeletal remodeling signaling pathways to decrease cancer cell growth and increase the recruitment of anti-tumor immune infiltrates. Methods: The dose escalation (3+3 design) and expansion are enrolling adult patients (pts) with advanced treatment-refractory solid tumors. ZB131 was administered IV over 60 minutes (without premedication) weekly. The starting dose of ZB131 is 0.3 mg/kg followed by 1,3, 9, 15 and 30 mg/kg. Primary objectives are safety, tolerability, and maximum tolerated dose/determination of Phase 2 dose. Secondary objectives are preliminary efficacy (RECIST v1.1), Pharmacokinetic (PK) and pharmacodynamic parameters in blood and paired tumor biopsies. Results: As of 31 Jan 2023, 24 pts had enrolled (9 PC, 6 CCA, 4 OC, 5 other). The median age was 59.5 yr (range, 35 – 84) with a median of 4 prior lines of therapy. The median ZB131 treatment duration is 5.3 weeks (range, 1 – 33). No dose-limiting toxicities were observed up to the dose of 30 mg/kg which is currently enrolling. Treatment-related adverse events (TRAEs) were grade 1/ 2: nausea (n=6), fatigue (n=5), anemia (n=3), diarrhea (n=2), flulike symptoms (n=2), and vomiting (n=2). Mild flu-like symptoms and nausea/vomiting were observed during or following infusion at doses of 9 mg/kg and above. Except for one episode of Gr 3 neutropenia at the 30 mg/kg dose, no other drug-related grade 3/4 TRAE’s were reported. Five pts had stable disease range, 12 – 33 weeks (2 PC, 1 CCA, 2 OC), with a 43% decrease in CA-125 observed in one OC pt. The PKs are linear and dose-proportional for all dose levels evaluated (estimated T½ of 6-9 days). No antidrug antibodies have been detected. Conclusions: Interim data from dose-escalation of this first-in-class, anti CSP antibody, demonstrates good tolerability with encouraging signs of activity and target engagement in heavily pretreated pts. Results support further clinical evaluation of ZB131 in dose-expansion cohorts including OC and including combination therapy with gemcitabine. Clinical trial information: NCT 05074472 .
First-in-human study of ZG19018, targeting KRAS G12C, as monotherapy in patients with advanced solid tumors.
Authors: Liu Rongrui , Qu Xiujuan , Yang Nong , Chai Xiaoli , Xu Jianming 
Published: June 2023

e15127 Background: ZG19018 tablet is a selective KRAS G12C inhibitor that inhibits the activation of KRAS G12C and multiple downstream signaling pathways. It showed very promising anti-tumor effects in preclinical studies. Here we report the preliminary results from a phase 1 dose escalation study that assessed the tolerability, safety, pharmacokinetics and efficacy of ZG19018 in patients (pts) with advanced solid tumors. Methods: This is an open-label, multi-center study in pts with KRAS G12C mutated solid tumors and progressed following prior standard therapies. The study consisted of a rapid dose-escalation phase for the low-dose groups (50 mg qd and 150 mg qd, orally) and a standard 3+3 design phase for the high-dose groups (300 mg qd, 300 mg bid and 450 mg bid, orally). The first treatment cycle (21 days) was defined as the dose-limiting toxicity (DLT) assessment period. Patients could continue to receive ZG19018 until one of the treatment discontinuation criteria was met. Tumor response was assessed by the investigator per RECIST1.1 criteria. Pharmacokinetics profiles were also assessed in all pts. Results: As of January 31st, 2023, 14 pts (8 males and 6 females) completed the DLT assessments, with a median age of 65 years. Of them, 11 (78.6%) were non-small cell lung cancer (NSCLC) pts, 2 (14.3%) with colorectal cancer (CRC), and 1 (7.1%) with cervical cancer (CESC); 12 pts (85.7%) had received ≥ 1 line of stand therapies and 2 pts (14.3%) had received ≥ 3 lines. The dose group of 450 mg bid was determined as the maximally administered dose, where 2 pts experienced a DLT (grade 3 γ-GGT elevation and grade 3 ALT elevation, respectively), therefore an additional dose group of 400 mg bid has been added and is currently undergoing. Treatment-related adverse events (TRAEs) occurred in 13 pts (92.9%), most frequent in nausea (42.9%), diarrhea (42.9%), vomiting (35.7%), AST elevation (35.7%), γ-GGT elevation (35.7%), ALT elevation (28.6%), hypertriglyceridemia (28.6%), blood creatine phosphokinase MB elevation (21.4%) and ALP elevation (21.4%). No SAE was reported. In 12 pts evaluated for the best overall responses, 2 (16.7%) had PR (1 NSCLC, 1 CRC), 6 (50%) had SD (4 NSCLC, 1 CRC，1 CESC) and 4 (33.3%) had PD (4 NSCLC). The maximum drug exposure of ZG19018 is 8 months in 1 patient with colorectal cancer who is SD and remaining in the study. The Cmax and AUC0-t increased from 50 mg qd to 450 mg bid approximately in dose proportion. Conclusions: ZG19018 is tolerable and demonstrates a good safety under the dose level of 450 mg bid. It also demonstrates preliminary antitumor effects in pts with solid tumors, with reasonable PK profiles. Clinical trial information: ChiCTR20220296 .
Preliminary results of a phase I, first-in-human, dose escalation study of IMM2902 in patients with HER2-expressing advanced solid tumors.
Authors: Meng Yanchun , Zhang Jian , Zhao Chuanhua , Cheng Ying , Zhu Liming , Song Zhengbo , Xu Nong , Wang Zhen , Wang Yanping , Du Yiqun , Jing Deqiang , Chen Dinglu , Qu Qiaofeng , Zhao Xiwen , Li Wei , Lu Qiying , Tian Wenzhi , Xu Jianming 
Published: June 2023

e15185 Background: IMM2902 is a novel recombinant bispecific fusion protein containing SIRPα binding domain trapped to the light chain of a humanized anti-HER2 antibody. With its high affinity to HER2 and CD47 on tumor cell membrane, IMM2902 can drive several anti-tumoral killing mechanisms such as directly targeting HER2 expressing tumor cells; restoring the phagocytic function of macrophages against tumor cells via CD47-SIRPα blockade; activating NK cells and macrophages mediated antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent cellular cytotoxicity (ADCC); and most importantly, inducing accelerated HER2 internalization and degradation. Phase I dose escalation studies of IMM2902 in advanced solid tumors are conducted in both China and the United States, here we present the preliminary results from China trial. Methods: The dose escalation study of IMM2902 was conducted following a modified 3+3 design to evaluate the safety and tolerability of the study drug and to determine the MTD/RP2D. IMM2902 was administered intravenously every week (QW) in 4-week cycles, and the first cycle was the DLT observation period. The tumor responses were evaluated based on RECIST v1.1. IMM2902 pharmacokinetics (PK) and pharmacodynamics (PD) were also evaluated. Results: As of 26 December 2022, a total of 16 subjects had received at least one dose of IMM2902 in 5 dose cohorts (0.03, 0.1, 0.3, 0.9 and 2.0 mg/kg). Of the 16 subjects, no DLTs were observed. Treatment related adverse events (TRAEs) occurred in all 16 subjects (100%), with 4 subjects (25%) reported to have grade 3 TRAEs. No subject discontinued IMM2902 treatment due to TRAEs. The most common TRAEs were platelet count decreased (62.5%), infusion related reaction (50%), and anemia (43.8%). The most common grade 3 or above TRAE was platelet count decreased (18.8%). One SAE (grade 3 gastrointestinal hemorrhage) was reported, which was unrelated to IMM2902. Among 13 evaluable subjects, 4 patients achieved SD (2 pts with gastric cancer at 0.1 mg/kg, 1 pt with skin cancer at 0.9 mg/kg, and 1 pt with breast cancer at 2.0 mg/kg). Preliminary PK analysis showed IMM2902 had a non-linear PK. Serum concentration of IMM2902 reached steady state after the third administration. Preliminary PD data showed that, beginning at 0.3 mg/kg, the number of peripheral CD3+ and CD8+ T-cells increased after 4 weeks of treatment. Conclusions: IMM2902 showed an encouraging preliminary safety, tolerability and anti-tumor activity up to 2.0 mg/kg. The phase I/II study is ongoing. Clinical trial information: ChiCTR20212375 .
Observational constraints on the modification of standard ΛCDM cosmology with dark radiation
Authors: Zhao Yifei , Qiang Ling-Xuan 
Published: June 2023

Abstract
We revisit a cosmological model modified by an extra “radiation-like” energy component in the Universe, which can be interpreted as many physical phenomena. Here, we derive the constraint on the energy density

from this modification with current cosmological observations, including Cosmic Microwave Background, Baryon Acoustic Oscillation, Observational Hubble Parameter data and Type Ia supernovae. Performing a Bayesian analysis gives

at 95% confidence level. Our work shows the dark radiation energy is small. Alleviating H
0 tension by introducing this term can also be interpreted as the systematic error caused by the numerical method.
Unexpected paths to cooperation on tied hyperbolic networks
Authors: Duh Maja , Gosak Marko , Perc Matjaž 
Published: June 2023

Abstract
Hyperbolic networks have high clustering, short average path lengths, and community structure, which are all properties that are commonly associated with social networks. As such, these networks constitute the perfect playing ground for probing factors that may affect public cooperation in realistic scenarios. And although much is already known about the evolution of cooperation on networks, we here consider the public goods game on tied hyperbolic networks, such that payoffs in one network layer influence the payoffs in the other and vice versa. We also consider random, assortative, and disassortative mixing in the networks to account for varying connections between players over time. While our research confirms the overall positive impact of interdependent payoffs, we also find that mixing on the network where cooperation thrives may strongly promote the cooperation in the other network, while destroying it completely in the former. We show that this is related to the mapping of lower payoffs from one network to the other, where cooperators in one network benefit from the failure of cooperators in the other network. Namely, as soon as the multiplication factor for the public goods is high enough to nullify the negative effects of mixing and cooperators thus recover, the positive effect on cooperation in the other network vanishes. We determine optimal conditions for this phenomenon in terms of the frequency of mixing and the strength of ties between the payoffs on both networks, and we discuss the implications of our research for enhanced cooperation in coupled populations, in particular in the light of mutual success not always being desirable for cooperation to thrive.