bluuebunny/crossref_metadata_2025_split huggingface dataset:
The developing landscape of combinatorial therapies of immune checkpoint blockade with DNA damage repair inhibitors for the treatment of breast and ovarian cancers
Authors: Zhu Lingling , Liu Jiewei , Chen Jiang , Zhou Qinghua 
Published: December 2021

AbstractThe use of immune checkpoint blockade (ICB) using antibodies against programmed death receptor (PD)-1, PD ligand (PD-L)-1, and cytotoxic T-lymphocyte antigen 4 (CTLA-4) has redefined the therapeutic landscape in solid tumors, including skin, lung, bladder, liver, renal, and breast tumors. However, overall response rates to ICB therapy remain limited in PD-L1-negative patients. Thus, rational and effective combination therapies will be needed to address ICB treatment resistance in these patients, as well as in PD-L1-positive patients who have progressed under ICB treatment. DNA damage repair inhibitors (DDRis) may activate T-cell responses and trigger inflammatory cytokines release and eventually immunogenic cancer cell death by amplifying DNA damage and generating immunogenic neoantigens, especially in DDR-defective tumors. DDRi may also lead to adaptive PD-L1 upregulation, providing a rationale for PD-L1/PD-1 blockade. Thus, based on preclinical evidence of efficacy and no significant overlapping toxicity, some ICB/DDRi combinations have rapidly progressed to clinical testing in breast and ovarian cancers. Here, we summarize the available clinical data on the combination of ICB with DDRi agents for treating breast and ovarian cancers and discuss the mechanisms of action and other lessons learned from translational studies conducted to date. We also review potential biomarkers to select patients most likely to respond to ICB/DDRi combination therapy.
Machine learning and deep learning predictive models for type 2 diabetes: a systematic review
Authors: Fregoso-Aparicio Luis , Noguez Julieta , Montesinos Luis , García-García José A. 
Published: December 2021

AbstractDiabetes Mellitus is a severe, chronic disease that occurs when blood glucose levels rise above certain limits. Over the last years, machine and deep learning techniques have been used to predict diabetes and its complications. However, researchers and developers still face two main challenges when building type 2 diabetes predictive models. First, there is considerable heterogeneity in previous studies regarding techniques used, making it challenging to identify the optimal one. Second, there is a lack of transparency about the features used in the models, which reduces their interpretability. This systematic review aimed at providing answers to the above challenges. The review followed the PRISMA methodology primarily, enriched with the one proposed by Keele and Durham Universities. Ninety studies were included, and the type of model, complementary techniques, dataset, and performance parameters reported were extracted. Eighteen different types of models were compared, with tree-based algorithms showing top performances. Deep Neural Networks proved suboptimal, despite their ability to deal with big and dirty data. Balancing data and feature selection techniques proved helpful to increase the model’s efficiency. Models trained on tidy datasets achieved almost perfect models.
Prevalence, antimicrobial susceptibility and virulence gene profiles of Arcobacter species isolated from human stool samples, foods of animal origin, ready-to-eat salad mixes and environmental water
Authors: Uljanovas Dainius , Gölz Greta , Brückner Vanessa , Grineviciene Audrone , Tamuleviciene Egle , Alter Thomas , Malakauskas Mindaugas 
Published: December 2021

Abstract
Background
Members of the genus Arcobacter are considered as emerging zoonotic food and waterborne pathogens that cause gastroenteritis and bacteremia in humans. However, the potential risk that Arcobacter species pose to public health remains unassessed in various countries, including Baltic states. Therefore, the aim of this study was to determine the prevalence, antimicrobial susceptibility and presence of putative virulence genes of Arcobacter isolates recovered from humans, food products and environmental water in Lithuania.

Results
A total of 1862 samples were collected and examined from 2018 to 2020 in the city of Kaunas. Overall, 11.2% (n = 208) of the samples were positive for the presence of Arcobacter spp. The highest prevalence was detected in chicken meat (36%), followed by environmental water (28.1%), raw cow milk (25%), ready-to-eat salad mixes (7.1%) and human stool (1.7%). A. butzleri was the most frequently isolated species (n = 192; 92.3%), followed by A. cryaerophilus (n = 16; 7.7%). Arcobacter spp. antimicrobial susceptibility testing revealed unimodally distributed aggregated minimal inhibitory concentrations (MICs) for gentamicin, tetracycline, ciprofloxacin, ampicillin and erythromycin. However, a bimodal distribution for azithromycin was found with 96.2% of determined MICs above the epidemiological cut-off value (ECOFF) defined for Campylobacter jejuni (0.25 µg/ml). Majority of the Arcobacter isolates (n = 187; 89.9%) showed high susceptibility to ciprofloxacin with MICs below or equal to the ECOFF value of 0.5 µg/ml. The putative virulence genes cadF (100%), ciaB (100%), cj1349 (99%), tlyA (99%), mviN (97.9%) and pldA (95.8%) were the predominant genes detected among A. butzleri isolates. In contrast, the mviN and ciaB genes were present in all, whereas cj1349 (12.5%), tlyA (25%) and hecA (12.5%) were only detected in few A. cryaerophilus isolates.

Conclusions
Our results demonstrate that food products and environmental water in Lithuania are frequently contaminated with Arcobacter spp. that carry multiple putative virulence genes. Furthermore, A. butzleri were isolated from 1.7% of inpatients. Fluoroquinolones and aminoglycosides were found to be more effective against Arcobacter in comparison to other antimicrobial agents. However, further studies are needed to determine the pathogenic mechanisms and factors that facilitate the spread of Arcobacter infections.
The evolved divergence of γ-secretase-susceptibility of homologous proteins Ngfrb and Nradd in zebrafish
Authors: Jayne Tanya , Newman Morgan , Baer Lachlan , Lardelli Michael 
Published: December 2021

Abstract
Objective
NGFR/p75NTR and NRADD/NRH proteins are closely related structurally and are encoded by genes that arose from a duplication event early in vertebrate evolution. The transmembrane domain (TMD) of NGFR is cleaved by γ-secretase but there is conflicting data around the susceptibility to γ-secretase cleavage of NRADD proteins. If NGFR and NRADD show differential susceptibility to γ-secretase, then they can be used to dissect the structural constraints determining substrate susceptibility. We sought to test this differential susceptibility.

Results
We developed labelled, lumenally-truncated forms of zebrafish Ngfrb and Nradd and a chimeric protein in which the TMD of Nradd was replaced with the TMD of Ngfrb. We expressed these in zebrafish embryos to test their susceptibility to γ-secretase cleavage by monitoring their stability using western immunoblotting. Inhibition of γ-secretase activity using DAPT increased the stability of only the Ngfrb construct. Our results support that only NGFR is cleaved by γ-secretase. Either NGFR evolved γ-secretase-susceptibility since its creation by gene duplication, or NRADD evolved to be refractory to γ-secretase. Protein structure outside of the TMD of NGFR is likely required for susceptibility to γ-secretase.
Would you like to be contacted about future research?
Authors: Newington Lisa , Alexander Caroline M. , Wells Mary 
Published: December 2021

AbstractMany research participants are willing to be contacted about future research opportunities, however this question is not always asked. Furthermore, if participants do consent for contact about future research, this information is not always accessible to other research teams. We discuss our experience of recruiting individuals who have previously taken part in healthcare research and suggest potential strategies to support this process and enable greater research participation.
Is kallikrein-8 a blood biomarker for detecting amnestic mild cognitive impairment? Results of the population-based Heinz Nixdorf Recall study
Authors: Schramm Sara , Jokisch Martha , Jöckel Karl-Heinz , Herring Arne , Keyvani Kathy 
Published: December 2021

Abstract
Background
Kallikrein-8 (KLK8) might be an early blood-biomarker of Alzheimer’s disease (AD). We examined whether blood KLK8 is elevated in persons with amnestic mild cognitive impairment (aMCI) which is a precursor of AD, compared to cognitively unimpaired (CU) controls.

Methods
Forty cases and 80 controls, matched by sex and age (± 3years), were participants of the longitudinal population-based Heinz Nixdorf Recall study (baseline: 2000–2003). Standardized cognitive performance was assessed 5 (T1) and 10 years after baseline (T2). Cases were CU at T1 and had incidental aMCI at T2. Controls were CU at T1 and T2. Blood KLK8 was measured at T2. Using multiple logistic regression the association between KLK8 in cases vs. controls was investigated by estimating odds ratios (OR) and 95% confidence intervals (95%CI), adjusted for inter-assay variability and freezing duration. Using receiver operating characteristic (ROC) analysis, the diagnostic accuracy of KLK8 was determined by estimating the area under the curve (AUC) and 95%CI (adjusted for inter-assay variability, freezing duration, age, sex).

Results
Thirty-seven participants with aMCI vs. 72 CU (36.7%women, 71.0±8.0 (mean±SD) years) had valid KLK8 measurements. Mean KLK8 was higher in cases than in controls (911.6±619.8 pg/ml vs.783.1±633.0 pg/ml). Fully adjusted, a KLK8 increase of 500pg/ml was associated with a 2.68 (1.05–6.84) higher chance of having aMCI compared to being CU. With an AUC of 0.92 (0.86–0.97), blood KLK8 was a strong discriminator for aMCI and CU.

Conclusion
This is the first population-based study to demonstrate the potential clinical utility of blood KLK8 as a biomarker for incipient AD.
Does lateral arm technique decrease the rate of clip migration in stereotactic and tomosynthesis-guided biopsies?
Authors: Weaver Olena , Cohen Ethan O. , Perry Rachel E. , Tso Hilda H. , Phalak Kanchan , Srinivasan Ashmitha , Bassett Roland , Leung Jessica W. T. 
Published: December 2021

Abstract
Background
Mammography-guided vacuum-assisted biopsies (MGVAB) can be done with stereotaxis or digital breast tomosynthesis guidance. Both methods can be performed with a conventional (CBA) or a lateral arm biopsy approach (LABA). Marker clip migration is relatively frequent in MGVAB (up to 44%), which in cases requiring surgery carries a risk of positive margins and re-excision. We aimed to compare the rates of clip migration and hematoma formation between the CBA and LABA techniques of prone MGVAB. Our HIPAA compliant retrospective study included all consecutive prone MGVAB performed in a single institution over a 20-month period. The LABA approach was used with DBT guidance; CBA utilized DBT or stereotactic guidance. The tissue sampling techniques were otherwise identical.

Results
After exclusion, 389 biopsies on 356 patients were analyzed. LABA was done in 97 (25%), and CBA in 292 (75%) cases. There was no statistical difference in clip migration rate with either 1 cm or 2 cm distance cut-off [15% for CBA and 10% for LABA for 1 cm threshold (p = 0.31); 5.8% or CBA and 3.1% or LABA for 2 cm threshold (p = 0.43)]. There was no difference in the rate of hematoma formation (57.5% in CDB and 50.5% in LABA, p = 0.24). The rates of technical failure were similar for both techniques (1.7% for CBA and 3% for LABA) with a combined failure rate of 1%.

Conclusions
LABA and CBA had no statistical difference in clip migration or hematoma formation rates. Both techniques had similar success rates and may be helpful in different clinical situations.
Evolutionary development of the cephalopod arm armature: a review
Authors: Fuchs Dirk , Hoffmann René , Klug Christian 
Published: December 2021

AbstractThe cephalopod arm armature is certainly one of the most important morphological innovations responsible for the evolutionary success of the Cephalopoda. New palaeontological discoveries in the recent past afford to review and reassess origin and homology of suckers, sucker rings, hooks, and cirri. Since a priori character state reconstructions are still ambiguous, we suggest and discuss three different evolutionary scenarios. Each of them is based on the following assumptions: (1) Neocoleoidea uniting extant Decabrachia and Octobrachia is monophyletic (= proostracum-bearing coleoids); (2) extinct Belemnitida and Diplobelida are stem decabrachians; (3) proostracum-less coleoids (Hematitida, Donovaniconida, Aulacoceratida) represent stem-neocoleoids; (4) Ammonoidea and Bactritoidea are stem coleoids. We consider a scenario where belemnoid hooks derived from primitive suckers as well-supported. Regarding belemnoid hooks and suckers as homologues implies that belemnoid, oegopsid, and probably ammonoid arm hooks arose through parallel evolution. Our conclusions challenge the widespread opinion, whereupon belemnoid hooks evolved de novo, and instead support earlier ideas formulated by Sigurd von Boletzky.
Out-of-pocket payments and catastrophic expenditures due to traffic injuries in Ouagadougou, Burkina Faso
Authors: Petitfour Laurène , Bonnet Emmanuel , Mathevet Isadora , Nikiema Aude , Ridde Valéry 
Published: December 2021

Abstract
Objective
To estimate the out-of-pocket expenditures linked to Road Traffic Injuries in Ouagadougou, Burkina Faso, as well as the prevalence of catastrophic expenditures among those out-of-pocket payments, and to identify the socio-economic determinants of catastrophic expenditures due to Road Traffic Injuries.

Methods
We surveyed every admission at the only trauma unit of Ouagadougou between January and July 2015 at the time of their admission, 7 days and 30 days later. We estimate a total amount of out-of-pocket expenditures paid by each patient. We considered an expense as catastrophic when it represented 10% at least of the annual global consumption of the patient’s household. We used linear models to determine if socio-economic characteristics were associated to a greater or smaller ratio between out-of-pocket payment and global annual consumption.

Findings
We surveyed 1323 Road injury victims three times (admission, Days 7 and 30). They paid in average 46,547 FCFA (83.64 US dollars) for their care, which represent a catastrophic expenditure for 19% of them. Less than 5% of the sample was covered by a health insurance scheme. Household economic status is found to be the first determinant of catastrophic health expenditure occurrence, exhibiting a significant and negative on the ratio between road injury expenditures and global consumption.

Conclusion
Our findings highlight the importance of developing health insurance schemes to protect poor households from the economic burden of road traffic injuries and improve equity in front of health shocks.
Awake prone position reduces work of breathing in patients with COVID-19 ARDS supported by CPAP
Authors: Chiumello Davide , Chiodaroli Elena , Coppola Silvia , Cappio Borlino Simone , Granata Claudia , Pitimada Matteo , Wendel Garcia Pedro David 
Published: December 2021

Abstract
Background
The use of awake prone position concomitant to non-invasive mechanical ventilation in acute respiratory distress syndrome (ARDS) secondary to COVID-19 has shown to improve gas exchange, whereas its effect on the work of breathing remain unclear. The objective of this study was to evaluate the effects of awake prone position during helmet continuous positive airway pressure (CPAP) ventilation on inspiratory effort, gas exchange and comfort of breathing.

Methods
Forty consecutive patients presenting with ARDS due to COVID-19 were prospectively enrolled. Gas exchange, esophageal pressure swing (ΔPes), dynamic transpulmonary pressure (dTPP), modified pressure time product (mPTP), work of breathing (WOB) and comfort of breathing, were recorded on supine position and after 3 h on prone position.

Results
The median applied PEEP with helmet CPAP was 10 [8–10] cmH2O. The PaO2/FiO2 was higher in prone compared to supine position (Supine: 166 [136–224] mmHg, Prone: 314 [232–398] mmHg, p < 0.001). Respiratory rate and minute ventilation decreased from supine to prone position from 20 [17–24] to 17 [15–19] b/min (p < 0.001) and from 8.6 [7.3–10.6] to 7.7 [6.6–8.6] L/min (p < 0.001), respectively. Prone position did not reduce ΔPes (Supine: − 7 [− 9 to − 5] cmH2O, Prone: − 6 [− 9 to − 5] cmH2O, p = 0.31) and dTPP (Supine: 17 [14–19] cmH2O, Prone: 16 [14–18] cmH2O, p = 0.34). Conversely, mPTP and WOB decreased from 152 [104–197] to 118 [90–150] cmH2O/min (p < 0.001) and from 146 [120–185] to 114 [95–151] cmH2O L/min (p < 0.001), respectively. Twenty-six (65%) patients experienced a reduction in WOB of more than 10%. The overall sensation of dyspnea was lower in prone position (p = 0.005).

Conclusions
Awake prone position with helmet CPAP enables a reduction in the work of breathing and an improvement in oxygenation in COVID-19-associated ARDS.
The impact of relative hypotension on acute kidney injury progression after cardiac surgery: a multicenter retrospective cohort study
Authors: Kotani Yuki , Yoshida Takuo , Kumasawa Junji , Kamei Jun , Taguchi Akihisa , Kido Koji , Yamaguchi Naoki , Kariya Takayuki , Nakasone Masato , Mikami Noriko , Koga Takahiro , Nakayama Izumi , Shibata Mami , Yoshida Tomonao , Nashiki Hiroshi , Karatsu Shinsuke , Nogi Kazutaka , Tokuhira Natsuko , Izawa Junichi 
Published: December 2021

Abstract
Background
Cardiac surgery is performed worldwide, and acute kidney injury (AKI) following cardiac surgery is a risk factor for mortality. However, the optimal blood pressure target to prevent AKI after cardiac surgery remains unclear. We aimed to investigate whether relative hypotension and other hemodynamic parameters after cardiac surgery are associated with subsequent AKI progression.

Methods
We retrospectively enrolled adult patients admitted to 14 intensive care units after elective cardiac surgery between January and December 2018. We defined mean perfusion pressure (MPP) as the difference between mean arterial pressure (MAP) and central venous pressure (CVP). The main exposure variables were time-weighted-average MPP-deficit (i.e., the percentage difference between preoperative and postoperative MPP) and time spent with MPP-deficit > 20% within the first 24 h. We defined other pressure-related hemodynamic parameters during the initial 24 h as exploratory exposure variables. The primary outcome was AKI progression, defined as one or more AKI stages using Kidney Disease: Improving Global Outcomes’ creatinine and urine output criteria between 24 and 72 h. We used multivariable logistic regression analyses to assess the association between the exposure variables and AKI progression.

Results
Among the 746 patients enrolled, the median time-weighted-average MPP-deficit was 20% [interquartile range (IQR): 10–27%], and the median duration with MPP-deficit > 20% was 12 h (IQR: 3–20 h). One-hundred-and-twenty patients (16.1%) experienced AKI progression. In the multivariable analyses, time-weighted-average MPP-deficit or time spent with MPP-deficit > 20% was not associated with AKI progression [odds ratio (OR): 1.01, 95% confidence interval (95% CI): 0.99–1.03]. Likewise, time spent with MPP-deficit > 20% was not associated with AKI progression (OR: 1.01, 95% CI 0.99–1.04). Among exploratory exposure variables, time-weighted-average CVP, time-weighted-average MPP, and time spent with MPP < 60 mmHg were associated with AKI progression (OR: 1.12, 95% CI 1.05–1.20; OR: 0.97, 95% CI 0.94–0.99; OR: 1.03, 95% CI 1.00–1.06, respectively).

Conclusions
Although higher CVP and lower MPP were associated with AKI progression, relative hypotension was not associated with AKI progression in patients after cardiac surgery. However, these findings were based on exploratory investigation, and further studies for validating them are required.
Trial Registration UMIN-CTR, https://www.umin.ac.jp/ctr/index-j.htm, UMIN000037074.
Anti-vascular endothelial growth factor therapy for age-related macular degeneration: a systematic review and network meta-analysis
Authors: Tricco Andrea C. , Thomas Sonia M. , Lillie Erin , Veroniki Areti Angeliki , Hamid Jemila S. , Pham Ba’ , Lee Taehoon , Agarwal Arnav , Sharpe Jane P. , Scott Alistair , Warren Rachel , Brahmbhatt Ronak , Macdonald Erin , Janoudi Ghayath , Muni Rajeev H. , Francisconi Carolina L. M. , Richter Trevor , Straus Sharon E. 
Published: December 2021

Abstract
Background
The comparative safety and efficacy between anti-vascular endothelial growth factor agents (anti-VEGFs) and between combined therapies for patients with neovascular age-related macular degeneration (nAMD) is unclear. We conducted a systematic review to examine the comparative safety and efficacy anti-VEGFs for adults with nAMD.

Methods
Studies were identified through MEDLINE, EMBASE, and Cochrane CENTRAL (inception to June 3, 2019), grey literature, and scanning reference lists. Two reviewers independently screened citations and full-text articles to identify randomized controlled trials (RCTs), extracted data, and appraised risk of bias. Pairwise random-effects meta-analysis and Bayesian network meta-analysis (NMA) were conducted. The primary outcomes were the proportion of patients experiencing moderate vision gain (≥ 15 letters on the Early Treatment Diabetic Retinopathy Study chart) and the proportion of patients experiencing moderate vision loss (≤ 15 letters).

Results
After screening 3647 citations and 485 potentially relevant full-text articles, 92 RCTs with 24,717 patients were included. NMA (34 RCTs, 8809 patients, 12 treatments) showed small differences among anti-VEGFs in improving the proportion of patients with moderate vision gain, with the largest for conbercept versus broluczumab (OR 0.15, 95% CrI: 0.05–0.56), conbercept versus ranibizumab (OR 0.17, 95% CrI: 0.05–0.59), conbercept versus aflibercept (OR 0.19, 95% CrI: 0.06–0.65), and conbercept versus bevacizumab (OR 0.2, 95% CrI: 0.06–0.69). In NMA (36 RCTs, 9081 patients, 13 treatments) for the proportion of patients with moderate vision loss, small differences were observed among anti-VEGFs, with the largest being for conbercept versus aflibercept (OR 0.24, 95% CrI: 0–4.29), conbercept versus brolucizumab (OR 0.24, 95% CrI: 0–4.71), conbercept versus bevacizumab (OR 0.26, 95% CrI: 0–4.65), and conbercept versus ranibizumab (OR 0.27, 95% CrI: 0–4.67).

Conclusion
The only observed differences were that ranibizumab, bevacizumab, aflibercept, and brolucizumab were statistically superior to conbercept in terms of the proportion of patients with nAMD who experienced moderate vision gain. However, this finding is based on indirect evidence through one small trial comparing conbercept with placebo. This does not account for drug-specific differences when assessing anatomic and functional treatment efficacy in variable dosing regimens.

Systematic review registration
PROSPERO registration number CRD42015022041.