bluuebunny/crossref_metadata_2025_split huggingface dataset:
ROS-induced PADI2 downregulation accelerates cellular senescence via the stimulation of SASP production and NFκB activation
Authors: Kim Hyun-Jung , Kim Woo-Jin , Shin Hye-Rim , Yoon Hee-In , Moon Jae-I , Lee Eunji , Lim Jin-Muk , Cho Young-Dan , Lee Mi-Hye , Kim Hong-Gee , Ryoo Hyun-Mo 
Published: February 2022

AbstractCellular senescence is closely related to tissue aging including bone. Bone homeostasis is maintained by the tight balance between bone-forming osteoblasts and bone-resorbing osteoclasts, but it undergoes deregulation with age, causing age-associated osteoporosis, a main cause of which is osteoblast dysfunction. Oxidative stress caused by the accumulation of reactive oxygen species (ROS) in bone tissues with aging can accelerate osteoblast senescence and dysfunction. However, the regulatory mechanism that controls the ROS-induced senescence of osteoblasts is poorly understood. Here, we identified Peptidyl arginine deiminase 2 (PADI2), a post-translational modifying enzyme, as a regulator of ROS-accelerated senescence of osteoblasts via RNA-sequencing and further functional validations. PADI2 downregulation by treatment with H2O2 or its siRNA promoted cellular senescence and suppressed osteoblast differentiation. CCL2, 5, and 7 known as the elements of the senescence-associated secretory phenotype (SASP) which is a secretome including proinflammatory cytokines and chemokines emitted by senescent cells and a representative feature of senescence, were upregulated by H2O2 treatment or Padi2 knockdown. Furthermore, blocking these SASP factors with neutralizing antibodies or siRNAs alleviated the senescence and dysfunction of osteoblasts induced by H2O2 treatment or Padi2 knockdown. The elevated production of these SASP factors was mediated by the activation of NFκB signaling pathway. The inhibition of NFκB using the pharmacological inhibitor or siRNA effectively relieved H2O2 treatment- or Padi2 knockdown-induced senescence and osteoblast dysfunction. Together, our study for the first time uncover the role of PADI2 in ROS-accelerated cellular senescence of osteoblasts and provide new mechanistic and therapeutic insights into excessive ROS-promoted cellular senescence and aging-related bone diseases.
On the second-order regularity of solutions to the parabolic p-Laplace equation
Authors: Feng Yawen , Parviainen Mikko , Sarsa Saara 
Published: February 2022

AbstractIn this paper, we study the second-order Sobolev regularity of solutions to the parabolic p-Laplace equation. For any p-parabolic function u, we show that $$D(\left| Du\right| ^{\frac{p-2+s}{2}}Du)$$

D
(

D
u

p
-
2
+
s

2

D
u
)

exists as a function and belongs to $$L^{2}_{\text {loc}}$$

L
loc
2

with $$s>-1$$

s
>
-
1

and $$1<p<\infty $$

1
<
p
<
∞

. The range of s is sharp.
Physiology dictated treatment after severe trauma: timing is everything
Authors: van Wessem Karlijn J. P. , Leenen Luke P. H. , Hietbrink Falco 
Published: February 2022

Abstract
Introduction
Damage control strategies in resuscitation and (fracture) surgery have become standard of care in the treatment of severely injured patients. It is suggested that damage control improves survival and decreases the incidence of organ failure. However, these strategies can possibly increase the risk of complications such as infections. Indication for damage control procedures is guided by physiological parameters, type of injury, and the surgeon’s experience. We analyzed outcomes of severely injured patients who underwent emergency surgery.

Methods
Severely injured patients, admitted to a level-1 trauma center ICU from 2016 to 2020 who were in need of ventilator support and required immediate surgical intervention ( ≤24 h) were included. Demographics, treatment, and outcome parameters were analyzed.

Results
Hundred ninety-five patients were identified with a median ISS of 33 (IQR 25–38). Ninety-seven patients underwent immediate definitive surgery (ETC group), while 98 patients were first treated according to damage control principles with abbreviated surgery (DCS group). Although ISS was similar in both groups, DCS patients were younger, suffered from more severe truncal injuries, were more frequently in shock with more severe acidosis and coagulopathy, and received more blood products. ETC patients with traumatic brain injury needed more often a craniotomy. Seventy-four percent of DCS patients received definitive surgery in the second surgical procedure. There was no difference in mortality, nor any other outcome including organ failure and infections.

Conclusions
When in severely injured patients treatment is dictated by physiology into either early definitive surgery or damage control with multiple shorter procedures stretched over several days combined with aggressive resuscitation with blood products, outcome is comparable in terms of complications.
Event-free survival after 68 Ga-PSMA-11 PET/CT in recurrent hormone-sensitive prostate cancer (HSPC) patients eligible for salvage therapy
Authors: Ceci Francesco , Rovera Guido , Iorio Giuseppe Carlo , Guarneri Alessia , Chiofalo Valeria , Passera Roberto , Oderda Marco , Dall’Armellina Sara , Liberini Virginia , Grimaldi Serena , Bellò Marilena , Gontero Paolo , Ricardi Umberto , Deandreis Désirée 
Published: February 2022

Abstract

Background/aim
Prostate-specific-membrane-antigen/positron emission tomography (PSMA-PET) detects with high accuracy disease-recurrence, leading to changes in the management of biochemically-recurrent (BCR) prostate cancer (PCa). However, data regarding the oncological outcomes of patients who performed PSMA-PET are needed. The aim of this study was to evaluate the incidence of clinically relevant events during follow-up in patients who performed PSMA-PET for BCR after radical treatment.

Materials and methods
This analysis included consecutive, hormone-sensitive, hormone-free, recurrent PCa patients (HSPC) enrolled through a prospective study. All patients were eligible for salvage therapy, having at least 24 months of follow-up after PSMA-PET. The primary endpoint was the Event-Free Survival (EFS), defined as the time between the PSMA-PET and the date of event/last follow-up. The Kaplan–Meier method was used to estimate the EFS curves. EFS was also investigated by Cox proportional hazards regression. Events were defined as death, radiological progression, or PSA recurrence after therapy.

Results
One-hundred and seventy-six (n = 176) patients were analyzed (median PSA 0.62 [IQR: 0.43–1.00] ng/mL; median follow-up of 35.4 [IQR: 26.5–40.3] months). The EFS was 78.8% at 1 year, 65.2% (2 years), and 52.2% (3 years). Patients experiencing events during study follow-up had a significantly higher median PSA (0.81 [IQR: 0.53–1.28] vs 0.51 [IQR: 0.36–0.80] ng/mL) and a lower PSA doubling time (PSAdt) (5.4 [IQR: 3.7–11.6] vs 12.7 [IQR: 6.6–24.3] months) (p < 0.001) compared to event-free patients. The Kaplan–Meier curves showed that PSA > 0.5 ng/mL, PSAdt ≤ 6 months, and a positive PSMA-PET result were associated with a higher event rate (p < 0.01). No significant differences of event rates were observed in patients who received changes in therapy management after PSMA-PET vs. patients who did not receive therapy changes. Finally, PSA > 0.5 ng/mL and PSAdt ≤ 6 months were statistically significant event-predictors in multivariate model (p < 0.001).

Conclusion
Low PSA and long PSAdt were significant predictors of longer EFS. A lower incidence of events was observed in patients having negative PSMA-PET, since longer EFS was significantly more probable in case of a negative scan.
Use of mathematical modelling to assess respiratory syncytial virus epidemiology and interventions: a literature review
Authors: Lang John C. 
Published: February 2022

AbstractRespiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infection worldwide, resulting in approximately sixty thousand annual hospitalizations of< 5-year-olds in the United States alone and three million annual hospitalizations globally. The development of over 40 vaccines and immunoprophylactic interventions targeting RSV has the potential to significantly reduce the disease burden from RSV infection in the near future. In the context of RSV, a highly contagious pathogen, dynamic transmission models (DTMs) are valuable tools in the evaluation and comparison of the effectiveness of different interventions. This review, the first of its kind for RSV DTMs, provides a valuable foundation for future modelling efforts and highlights important gaps in our understanding of RSV epidemics. Specifically, we have searched the literature using Web of Science, Scopus, Embase, and PubMed to identify all published manuscripts reporting the development of DTMs focused on the population transmission of RSV. We reviewed the resulting studies and summarized the structure, parameterization, and results of the models developed therein. We anticipate that future RSV DTMs, combined with cost-effectiveness evaluations, will play a significant role in shaping decision making in the development and implementation of intervention programs.
Prognostic impact of complete metastasectomy in metastatic renal cell carcinoma in the era of immuno-oncology-based combination therapies
Authors: Stühler Viktoria , Herrmann Lisa , Maas Moritz , Walz Simon , Rausch Steffen , Stenzl Arnulf , Bedke Jens 
Published: February 2022

Abstract
Purpose
Complete metastasectomy of renal cell carcinoma (RCC) is receding into the past due to the progress of immuno-oncology-based combinations (IO) in systemic therapy. The prognostic impact of curative intended complete metastasectomy vs. immediate IO-based therapy or tyrosine kinase inhibition (TKI) on progression-free survival (PFS) and cancer-specific survival (CSS) was investigated in the first-line setting.

Methods
205 patients with synchronous or metachronous metastasis received complete metastasectomy (n = 80) or systemic therapy (n = 125, TKI: 87, TKI–IO: 13, IO–IO: 25) as first-line therapy. The prognostic impact of these therapies was assessed using Cox regression and Kaplan–Meier analyses.

Results
First-line complete metastasectomy significantly improved CSS compared to both TKI monotherapy (6.1 vs. 2.6 years, HR 0.45, p < 0.001) and IO-based combination therapy (IO–IO/TKI–IO, 6.1 vs. 3.5 years, HR 0.28, p = 0.007). Repetitive complete metastasectomy without ever receiving systemic therapy vs. systemic therapy in first-line significantly prolonged CSS (11.3 vs. 3.1 years, HR 0.34, p = 0.002). First-line complete metastasectomy and subsequent systemic therapy at tumor progression was associated with a significant CSS benefit vs. systemic therapy (5.8 vs. 3.1 years, HR 0.53, p = 0.003), also compared to IO-based combinations (5.8 vs. 3.5 years, HR 0.30, p = 0.017). Median PFS was improved by IO-based therapy compared to TKI monotherapy in the first-line setting (HR 0.61, p = 0.05), with maximal benefit of the TKI–IO combination vs. TKI monotherapy (HR 0.27, p = 0.01), as well as compared to PFS of complete metastasectomy (HR 0.34, p = 0.035).

Conclusion
Despite the progress of IO-based combination therapies in first line, complete metastasectomy remains an integral part of the multimodality treatment of metastatic RCC.
Real-world anticoagulatory treatment after percutaneous mitral valve repair using MitraClip: a retrospective, observational study on 1300 patients
Authors: Hohmann Christopher , Ludwig Marion , Walker Jochen , Iliadis Christos , Schipper Jan-Hendrik , Baldus Stephan , Pfister Roman 
Published: February 2022

Abstract
Aims
This study sought to investigate current anticoagulatory treatment patterns and clinical outcome in patients undergoing transcatheter mitral valve repair (MitraClip).

Methods and results
In a retrospective study of a German claims database (InGef research database), anticoagulatory treatment regimens were assessed using any drug prescription post discharge within the first 90 days after MitraClip procedure. Clinical events between 30 days and 6 months were examined by treatment regime. The study population comprised 1342 patients undergoing MitraClip procedure between 2014 and 2018. 22.4% received antiplatelet monotherapy, 20.8% oral anticoagulation (OAC) plus antiplatelet therapy, 19.4% OAC monotherapy, 11.7% dual antiplatelet therapy, 2.8% triple therapy and 21.0% did not receive any anticoagulatory drugs. 63% of patients with OAC received non-vitamin-K antagonist oral anticoagulants (NOAC). A total of 168 patients were newly prescribed OAC after MitraClip, of whom 12 patients (7.1%) had no diagnosis of atrial fibrillation or venous thromboembolism. 40% of patients with OAC prior to MitraClip did not have any OAC after MitraClip. The adjusted risk of all-cause mortality was significantly increased in patients with no anticoagulatory treatment (HR 3.84, 95% CI 2.33–6.33, p < 0.0001) when compared to antiplatelet monotherapy whereas the other regimes were not significantly different.

Conclusions
This large real-world data analysis demonstrates a heterogeneous spectrum of prescriptions for anticoagulant therapies after MitraClip. Considering relevant differences in clinical outcome across treatment groups, major effort is warranted for controlled trials in order to establish evidence-based recommendations on anticoagulatory treatment after percutaneous mitral valve repair.

Graphical abstract
Gut microbiota-dependent metabolite trimethylamine N-oxide (TMAO) and cardiovascular risk in patients with suspected functionally relevant coronary artery disease (fCAD)
Authors: Amrein Melissa , Li Xinmin S. , Walter Joan , Wang Zeneng , Zimmermann Tobias , Strebel Ivo , Honegger Ursina , Leu Kathrin , Schäfer Ibrahim , Twerenbold Raphael , Puelacher Christian , Glarner Noemi , Nestelberger Thomas , Koechlin Luca , Ceresa Benjamin , Haaf Philip , Bakula Adam , Zellweger Michael , Hazen Stanley L. , Mueller Christian 
Published: February 2022

Abstract
Background
Trimethylamine N-oxide (TMAO) has been associated with cardiovascular outcomes. However, the diagnostic value of TMAO and its precursors have not been assessed for functionally relevant coronary artery disease (fCAD) and its prognostic potential in this setting needs to be evaluated.

Methods
Among 1726 patients with suspected fCAD serum TMAO, and its precursors betaine, choline and carnitine, were quantified using liquid chromatography tandem mass spectrometry. Diagnosis of fCAD was performed by myocardial perfusion single photon emission tomography (MPI-SPECT) and coronary angiography blinded to marker concentrations. Incident all-cause death, cardiovascular death (CVD) and myocardial infarction (MI) were assessed during 5-years follow-up.

Results
Concentrations of TMAO, betaine, choline and carnitine were significantly higher in patients with fCAD versus those without (TMAO 5.33 μM vs 4.66 μM, p < 0.001); however, diagnostic accuracy was low (TMAO area under the receiver operating curve [AUC]: 0.56, 95% CI [0.53–0.59], p < 0.001). In prognostic analyses, TMAO, choline and carnitine above the median were associated with significantly (p < 0.001 for all) higher cumulative events for death and CVD during 5-years follow-up. TMAO remained a significant predictor for death and CVD even in full models adjusted for renal function (HR = 1.58 (1.16, 2.14), p = 0.003; HR = 1.66 [1.07, 2.59], p = 0.025). Prognostic discriminative accuracy for TMAO was good and robust for death and CVD (2-years AUC for CVD 0.73, 95% CI [0.65–0.80]).

Conclusion
TMAO and its precursors, betaine, choline and carnitine were significantly associated with fCAD, but with limited diagnostic value. TMAO was a strong predictor for incident death and CVD in patients with suspected fCAD.

Clinical trial registration
NCT01838148.

Graphical abstract
Associations of dairy, meat, and fish intakes with risk of incident dementia and with cognitive performance: the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD)
Authors: Ylilauri Maija P. T. , Hantunen Sari , Lönnroos Eija , Salonen Jukka T. , Tuomainen Tomi-Pekka , Virtanen Jyrki K. 
Published: February 2022

Abstract
Purpose
To investigate if dairy, meat, and fish intakes associate with dementia and cognitive performance.

Methods
We included 2497 dementia-free men from Eastern Finland, aged 42–60 years in 1984–1989 at the baseline examinations. Data on cognitive tests [Mini Mental State Exam (MMSE), trail making test (TMT), verbal fluency test (VFL), selective reminding test (SRT), and Russell’s adaptation of the visual reproduction test (VRT)] at the 4-year re-examinations were available for 482 men and on the ApoE phenotype for 1259 men. Data on dementia events were obtained by linkage to national health registers. Diet was assessed with baseline 4-day food records. Cox regression and analysis of covariance were used for analyses.

Results
During a mean 22-year follow-up, 337 men had a dementia diagnosis. Among the foods, only cheese intake associated with dementia risk (hazard ratio in the highest vs. the lowest quartile = 0.72, 95% confidence interval = 0.52–0.99, P-trend = 0.05). In the cognitive tests, higher non-fermented dairy and milk intakes associated with worse verbal fluency (VFT). Higher processed red meat intake associated with worse verbal (SRT) and visual memory (VRT), whereas higher unprocessed red meat intake associated with better general cognitive functioning (MMSE) and processing speed and executive functioning (TMT). Higher fish intake associated with better verbal memory (SRT). Among APOE-ε4 carriers, especially non-fermented dairy intake associated with higher risk of dementia outcomes, and higher fish intake indicated better cognitive performance.

Conclusion
Although higher intake of some food groups associated with cognitive performance, we found little evidence for associations with dementia risk.
Occupational exposure to physicians working with a Zero-Gravity™ protection system in haemodynamic and electrophysiology labs and the assessment of its performance against a standard ceiling suspended shield
Authors: Domienik-Andrzejewska Joanna , Mirowski Mateusz , Jastrzębski Marek , Górnik Tomasz , Masiarek Konrad , Warchoł Izabela , Grabowicz Włodzimierz 
Published: February 2022

AbstractA two centre clinical study was performed to analyse exposure levels of cardiac physicians performing electrophysiology and haemodynamic procedures with the use of state of the art Zero-Gravity™ radiation protective system (ZG). The effectiveness of ZG was compared against the commonly used ceiling suspended lead shield (CSS) in a haemodynamic lab. The operator’s exposure was assessed using thermoluminescent dosimeters (TLDs) during both ablation (radiofrequency ablation (RFA) and cryoablation (CRYA)) and angiography and angioplasty procedures (CA/PCI). The dosimeters were placed in multiple body regions: near the left eye, on the left side of the neck, waist and chest, on both hands and ankles during each measurement performed with the use of ZG. In total 29 measurements were performed during 105 procedures. To compare the effectiveness of ZG against CSS an extra 80 measurements were performed with the standard lead apron, thyroid collar and ceiling suspended lead shield during CA/PCI procedures. For ZG, the upper values for the average eye lens and whole body doses per procedure were 4 µSv and 16 µSv for the left eye lens in electrophysiology lab (with additionally used CSS) and haemodynamic lab (without CSS), respectively, and about 10 µSv for the remaining body parts (neck, chest and waist) in both labs. The skin doses to hands and ankles non-protected by the ZG were 5 µSv for the most exposed left finger and left ankle in electrophysiology lab, while in haemodynamic lab 150 µSv and 17 µSv, respectively. The ZG performance was 3 times (p < 0.05) and at least 15 times (p < 0.05) higher for the eye lenses and thoracic region, respectively, compared to CSS (with dosimeters on the apron/collar). However, when only ZG was used slightly higher normalised doses were observed for the left finger compared to CSS (5.88e − 2 Sv/Gym2 vs. 4.31 e − 2 Sv/Gym2, p = 0.016). The study results indicate that ZG performance is superior to CSS. It can be simultaneously used with the ceiling suspended lead shield to ensure the protection to the hands as long as this is not obstructive for the work.
Cuticular hydrocarbons for the identification and geographic assignment of empty puparia of forensically important flies
Authors: Moore Hannah , Lutz Lena , Bernhardt Victoria , Drijfhout Falko P. , Cody Robert B. , Amendt Jens 
Published: February 2022

AbstractResearch in social insects has shown that hydrocarbons on their cuticle are species-specific. This has also been proven for Diptera and is a promising tool for identifying important fly taxa in Forensic Entomology. Sometimes the empty puparia, in which the metamorphosis to the adult fly has taken place, can be the most useful entomological evidence at the crime scene. However, so far, they are used with little profit in criminal investigations due to the difficulties of reliably discriminate among different species. We analysed the CHC chemical profiles of empty puparia from seven forensically important blow flies Calliphora vicina, Chrysomya albiceps, Lucilia caesar, Lucilia sericata, Lucilia silvarum, Protophormia terraenovae, Phormia regina and the flesh fly Sarcophaga caerulescens. The aim was to use their profiles for identification but also investigate geographical differences by comparing profiles of the same species (here: C. vicina and L. sericata) from different regions. The cuticular hydrocarbons were extracted with hexane and analysed using gas chromatography-mass spectrometry. Our results reveal distinguishing differences within the cuticular hydrocarbon profiles allowing for identification of all analysed species. There were also differences shown in the profiles of C. vicina from Germany, Spain, Norway and England, indicating that geographical locations can be determined from this chemical analysis. Differences in L. sericata, sampled from England and two locations in Germany, were less pronounced, but there was even some indication that it may be possible to distinguish populations within Germany that are about 70 km apart from one another.