bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comparison among PCNL, Miniperc and Ultraminiperc for lower calyceal stones between 1 and 2 cm: a prospective, comparative, multicenter and randomised study
Authors: Bozzini Giorgio , Aydogan Tahsin Batuhan , Müller Alexander , Sighinolfi Maria Chiara , Besana Umberto , Calori Alberto , Lorenzo Berti , Govorov Alexander , Pushkar Dmitry Y. , Pini Giovannalberto , Pastore Antonio Luigi , Romero-Otero Javier , Rocco Bernardo , Buizza Carlo 
Published: June 2020

AbstractBackgroundConventional Percutaneous Lithotripsy (PCNL) has been an effective, successful and easy approach for especially > 1 cm sized calyceal stones however risks of complications and nephron loss are inevitable. Our aim is to compare the efficacy and safety of PCNL, MiniPerc (MP) and UltraMiniPerc (UMP) for lower calyceal stones between 1 and 2 cm with a multicenter prospective randomized study.MethodsBetween January 2015 and June 2018, 132 consecutive patients with single lower calyceal stone were enrolled. Patients were randomized in three groups; A: PCNL; B: MP; C: UMP. 44 patients for the Group A, 47 for Group B and 41 for Group C. Exclusion criterias were the presence of coagulation impairments, age of < 18 or > 75, presence of infection or serious comorbidities. Patients were controlled with computerized tomography scan after 3 months. A negative CT or an asymptomatic patient with stone fragments < 3 mm size were the criteria to assess the stone-free status. Patient characteristics, stone free rates (SFR) s, complications and re-treatment rates were analyzed.ResultsThe mean stone size were 16.38, 16.82 and 15.23 mm respectively in Group A, B and C(p = 0.34). The overall SFR was significantly higher in Group A (86.3%) and B (82.9%) as compared to Group C (78%)(p < 0.05). The re-treatment rate was significantly higher in Group C (12.1%) and complication rates was higher in Group A (13.6%) as compared to others(p < 0.05). The hospitalization was significantly shorter in Group C compared to Group A (p = 0.04).ConclusionsPCNL and MP showed higher efficacy than UMP to obtain a better SFR. Auxiliary and re-treatment rates were higher in UMP. On the other hand for such this kind of stones PCNL had more complications. Overall evaluation favors MP as a better indication in stones 1–2 cm size.
Estimating the contribution of different age strata to vaccine serotype pneumococcal transmission in the pre vaccine era: a modelling study
Authors: Flasche Stefan , Lipsitch Marc , Ojal John , Pinsent Amy 
Published: June 2020

Abstract
Background
Herd protection through interruption of transmission has contributed greatly to the impact of pneumococcal conjugate vaccines (PCVs) and may enable the use of cost-saving reduced dose schedules. To aid PCV age targeting to achieve herd protection, we estimated which population age groups contribute most to vaccine serotype (VT) pneumococcal transmission.

Methods
We used transmission dynamic models to mirror pre-PCV epidemiology in England and Wales, Finland, Kilifi in Kenya and Nha Trang in Vietnam where data on carriage prevalence in infants, pre-school and school-aged children and adults as well as social contact patterns was available. We used Markov Chain Monte Carlo methods to fit the models and then extracted the per capita and population-based contribution of different age groups to VT transmission.

Results
We estimated that in all settings, < 1-year-old infants cause very frequent secondary vaccine type pneumococcal infections per capita. However, 1–5-year-old children have the much higher contribution to the force of infection at 51% (28, 73), 40% (27, 59), 37% (28, 48) and 67% (41, 86) of the total infection pressure in E&W, Finland, Kilifi and Nha Trang, respectively. Unlike the other settings, school-aged children in Kilifi were the dominant source for VT infections with 42% (29, 54) of all infections caused. Similarly, we estimated that the main source of VT infections in infants are pre-school children and that in Kilifi 39% (28, 51) of VT infant infections stem from school-aged children whereas this was below 15% in the other settings.

Conclusion
Vaccine protection of pre-school children is key for PCV herd immunity. However, in high transmission settings, school-aged children may substantially contribute to transmission and likely have waned much of their PCV protection under currently recommended schedules.
Upregulation of ARHGAP30 attenuates pancreatic cancer progression by inactivating the β-catenin pathway
Authors: Zhou Yongping , Hua Zhiyuan , Zhu Ye , Wang Liying , Chen Fangming , Shan Ting , Zhou Yunhai , Dai Tu 
Published: June 2020

Abstract
Background
Pancreatic cancer is a highly malignant gastrointestinal cancer that can widely metastasize during the early stage of disease, and it is associated with one of the worst prognoses among cancers. In this study, we aimed to investigate the function of Rho GTPase-activating protein 30 (ARHGAP30) in pancreatic cancer cells and thus propose a novel therapy for pancreatic cancer.

Methods
ARHGAP30 expression in tumor tissues from patients with pancreatic cancer as well as cell lines was detected using immunohistochemistry (IHC), real-time polymerase chain reaction, and western blotting. Cell proliferation, transwell, and apoptosis assays were performed and the levels of related proteins were determined after ARHGAP30 knockdown or overexpression. Additionally, in vivo experiments were performed on nude mice.

Results
ARHGAP30 expression was found to be significantly increased in tumor tissues from patients with pancreatic cancer as well as in pancreatic cancer cell lines. IHC and prognostic analyses indicated that patients with high ARHGAP30 expression had a good prognosis. ARHGAP30 overexpression significantly decreased pancreatic cancer cell proliferation and metastasis; promoted apoptosis; reduced β-catenin, B-cell lymphoma 2 (Bcl-2), matrix metalloproteinase-2 (MMP2), and MMP9 expression; and increased Bcl-2-associated X protein (Bax) and cleaved caspase-3 expression. ARHGAP30 knockdown elicited the opposite effects. The effects of ARHGAP30 knockdown were potently attenuated by the β-catenin inhibitor XAV939. ARHGAP30 knockdown-induced RHOA activity was potently attenuated by the RHOA inhibitor CCG1423. In vivo, ARHGAP30 overexpression significantly inhibited lung metastasis in nude mice and increased the survival of mice with lung metastases.

Conclusions
Our findings indicate that ARHGAP30 may function as a tumor suppressor in pancreatic cancer progression by regulating the expression of related genes and the β-catenin pathway.
Transformative medical education: must community-based traineeship experiences be part of the curriculum? A qualitative study
Authors: Massé Julie , Dupéré Sophie , Martin Élisabeth , Lévesque Martine C. 
Published: June 2020

AbstractBackgroundThere are shortcomings in medical practitioners’ capacity to adapt to the particular needs of people experiencing circumstances of social vulnerability. Clinical traineeships create opportunities for the acquisition of knowledge, competencies, attitudes, and behaviors. However, some authors question the learnings to be made through classical clinical training pathways. This article explores the learnings gained from a traineeship experience within a community-based clinical setting intended for patients experiencing social vulnerability and operating under an alternative paradigm of care. To our knowledge, there is little research intended to identify and understand what medical trainees gain from their experience in such contexts.MethodsThis exploratory qualitative study is based on twelve interviews with practicing physicians who completed a traineeship atLa Maison Bleue(Montreal, Canada) and three interviews conducted with key informants involved in traineeship management. Based on Mezirow’s theory of transformational learning, data were analyzed according to L’Écuyer’s principles of qualitative content analysis. NVivo software was used.ResultsThe main learnings gained through the traineeship are related to (1) greater awareness of beliefs, assumptions and biases through prejudice deconstruction, cultural humility and critical reflection on own limitations, power and privileges; (2) the development of critical perspectives regarding the health care system; (3) a renewed vision of medical practice involving a less stigmatizing approach, advocacy, empowerment, interdisciplinarity and intersectorality; and (4) strengthened professional identity and future practice orientation including confirmation of interest for community-based practice, the identification of criteria for choosing a future practice setting, and commitment to becoming an actor of social change. Certain characteristics of the setting, the patients and the learner’s individual profile are shown to be factors that promote these learnings.ConclusionsThis article highlights how a traineeship experience within a clinical setting intended for a clientele experiencing circumstances of social vulnerability and operating under an alternative paradigm presents an opportunity for transformative learning and health practice transformation toward renewed values of health equity and social justice. Our findings suggest medical traineeships in community-based clinical settings are a promising lead to foster the development of fundamental learnings that are conducive to acceptable and equitable care for people experiencing social vulnerability.
SARS-CoV-2 COVID-19 susceptibility and lung inflammatory storm by smoking and vaping
Authors: Kaur Gagandeep , Lungarella Giuseppe , Rahman Irfan 
Published: June 2020

AbstractThe current pandemic of COVID-19 has caused severe morbidity and mortality across the globe. People with a smoking history have severe disease outcomes by COVID-19 infection. Epidemiological studies show that old age and pre-existing disease conditions (hypertension and diabetes) result in severe disease outcome and mortality amongst COVID-19 patients. Evidences suggest that the S1 domain of the SARS-CoV-2 (causative agent of COVID-19) membrane spike has a high affinity towards the angiotensin-converting enzyme 2 (ACE2) receptor found on the host’s lung epithelium. Likewise, TMPRSS2 protease has been shown to be crucial for viral activation thus facilitating the viral engulfment. The viral entry has been shown to cause ‘cytokine storm’ involving excessive production of pro-inflammatory cytokines/chemokines including IL-6, TNF-α, IFN-γ, IL-2, IL-7, IP-10, MCP-3 or GM-CSF, which is augmented by smoking. Future research could target these inflammatory-immunological responses to develop effective therapy for COVID-19. This mini-review provides a consolidated account on the role of inflammation and immune responses, proteases, and epithelial permeability by smoking and vaping during SARS-CoV2 infection with future directions of research, and provides a list of the potential targets for therapies particularly controlling cytokine storms in the lung.
A comprehensive custom panel evaluation for routine hereditary cancer testing: improving the yield of germline mutation detection
Authors: Velázquez Carolina , Lastra Enrique , Avila Cobos Francisco , Abella Luis , de la Cruz Virginia , Hernando Blanca Ascensión , Hernández Lara , Martínez Noemí , Infante Mar , Durán Mercedes 
Published: June 2020

Abstract
Background
In the context of our Regional Program of Hereditary Cancer, individuals fulfilling the criteria are tested for germline mutations to subsequently establish the clinical management. Our standard diagnostic approach focuses on sequencing a few classic high-risk genes, a method that frequently renders uninformative genetic results. This study aims to examine the improved yield offered by an On-Demand panel.

Methods
We designed an On-Demand panel for the analysis of 35-genes associated with inherited cancer susceptibility in a total of 128 cases of Hereditary Breast and Ovarian Cancer (HBOC) and Hereditary Nonpolyposis Colorectal Cancer (HNPCC).

Results
Eighteen deleterious mutations were detected, in both routinely (BRCA2, MLH1, MSH2, PMS2) and non-routinely (ATM, BLM, BRIP1, CHEK2, MUTYH) tested genes. The screening extended to 35 genes rendered by patients carrying several- up to 6-Variants of Unknown Significance (VUS). Moreover, we confirmed the splicing disruption at RNA level for a not previously reported BRIP1 splicing mutation. Using an On-Demand panel, we identified 18 pathogenic mutation carriers, seven of which would have gone unnoticed with traditional analysis.

Conclusions
Our results reinforce the utility of NGS gene panels in the diagnostic routine to increase the performance of genetic testing, especially in individuals from families with overlapping cancer phenotypes.
Extrasynaptic CaMKIIα is involved in the antidepressant effects of ketamine by downregulating GluN2B receptors in an LPS-induced depression model
Authors: Tang Xiao-Hui , Zhang Guang-Fen , Xu Ning , Duan Gui-Fang , Jia Min , Liu Ru , Zhou Zhi-Qiang , Yang Jian-Jun 
Published: June 2020

AbstractBackgroundA subanesthetic dose of ketamine provides rapid and effective antidepressant effects, but the molecular mechanism remains elusive. It has been reported that overactivation of extrasynaptic GluN2B receptors is associated with the antidepressant effects of ketamine and the interaction between GluN2B and calcium/calmodulin-dependent protein kinase IIα (CaMKIIα) is important for GluN2B localization and activity. Here, we tested whether changes of CaMKIIα and GluN2B are involved in the antidepressant effects of ketamine.MethodsLipopolysaccharide (LPS) was injected intraperitoneally (i.p.) into male C57BL/6 mice. For the interventional study, mice were administrated with ketamine (10 mg/kg, i.p.) or a CaMKIIα inhibitor KN93. Behavioral alterations were evaluated by open-field, novelty-suppressed feeding, and forced-swimming tests. Physiological functions were evaluated by the body weight and fur coat state of mice. The levels of p-CaMKIIα, CaMKIIα, p-GluN2B, GluN2B, p-CREB, CREB, BDNF, GluR1, and GluR2 in the hippocampus were detected by western blotting. The interaction between GluN2B and CaMKIIα was studied using immunoprecipitation assay and small interfering RNA (siRNA) assays. The colocalizations of GluN2B/PSD95 and p-GluN2B/PSD95 were detected by immunofluorescence. The long-term potentiation (LTP) in SC-CA1 of the hippocampus was detected by electrophysiology.ResultsLPS injection induced depression-like behaviors, which were accompanied by significant increases in extrasynaptic p-CaMKIIα expression, extrasynaptic GluN2B localization, and phosphorylation and decreases in p-CREB, BDNF, and GluR1 expressions and LTP impairment. These changes were prevented by ketamine administration. Immunoprecipitation assay revealed that LPS induced an increase in the p-CaMKIIα–GluN2B interaction, which was attenuated by ketamine administration. SiRNA assay revealed that CaMKIIα knockdown reduced the level and number of clusters of GluN2B in the cultured hippocampal neurons. KN93 administration also reduced extrasynaptic p-CaMKIIα expression, extrasynaptic GluN2B localization, and phosphorylation and exerted antidepressant effects.ConclusionThese results indicate that extrasynaptic CaMKIIα plays a key role in the cellular mechanism of ketamine’s antidepressant effect and it is related to the downregulation of extrasynaptic GluN2B localization and phosphorylation.
Classical and lectin complement pathways and markers of inflammation for investigation of susceptibility to infections among healthy older adults
Authors: LaFon David C. , Thiel Steffen , Kim Young-il , Dransfield Mark T. , Nahm Moon H. 
Published: June 2020

Abstract
Background
There is increasing recognition of the significance of chronic, low-level inflammation in older adults, or “inflammaging.” Innate immune responses and host-bacterial interactions are recognized as key factors in inflammaging. Inflammatory cytokine IL-6, and complement protein C1q have been identified as biomarkers for the development of frailty and aging-related diseases. Older adults are also susceptible to infections with serotypes of Streptococcus pneumoniae that bind ficolin-2, a component of the lectin complement pathway, and low ficolin-2 levels could possibly be involved in such susceptibility.

Methods
The aim of our study was to evaluate complement pathway components and biomarkers for inflammaging among older adults in order to investigate potential innate immune mechanisms that may account for susceptibility to infections in this population. We compared inflammatory markers, as well as components/activity of the classical and lectin complement pathways between healthy older and younger adults. We hypothesized that older adults would have higher levels of inflammatory markers and C1q, and lower levels of lectin pathway components. Older (≥70 years old) and younger (19–54 years old) adults without significant smoking history or chronic medical conditions were eligible for participation. Inflammatory markers (IL-6, TNF-α, CRP), classical complement pathway activity (CH50) and protein levels (C1q, C3, C4), and lectin pathway (MBL levels/activity, CL-L1, MASP-1/2/3, MAp44, MAp19, and H/M/L-ficolin) were compared between groups.

Results
Older adults had significantly higher mean levels of IL-6 and TNF-α. There were no significant differences in lectin pathway components between older and younger adults. Unexpectedly, mean C1q was significantly higher in the younger group in both unadjusted and adjusted analyses. There was also a significant association between race and C1q levels, but this association did not completely account for the observed differences between age groups.

Conclusions
We did not observe deficiencies in lectin pathway components to account for increased susceptibility to ficolin-binding serotypes of S. pneumoniae. Elevated levels of inflammatory cytokines in older adults are suggestive of inflammaging. However, the observed age and race-associated changes in C1q have not been previously reported in the populations included in our study. These findings are relevant to the investigation of C1q in aging-related pathology, and for its proposed role as a biomarker for frailty and disease.
Assessment of two POC technologies for CD4 count in Morocco
Authors: Elharti Elmir , Abbadi Halima , Bensghir Rajae , Marhoum El Filali Kamal , Elmrabet Hajar , Oumzil Hicham 
Published: June 2020

Abstract
Background
In the era of “test and treat strategy”, CD4 testing remains an important tool for monitoring HIV-infected individuals. Since conventional methods of CD4 count measurement are costly and cumbersome, POC CD4 counting technique are more affordable and practical for countries with limited resources. Before introducing such methods in Morocco, we decided to assess their reliability.

Methods
In this study 92 blood samples from HIV-infected patients, were tested by PIMA and FACSPresto to derive CD4 count. Flow cytometry using FacsCalibur, was used as reference method for CD4 count comparison. Linear regression, Bland–Altman analysis were performed to assess correlation and agreement between these POC methods and the reference method. In addition, sensitivity and specificity, positive predictive value (PPV), negative predictive value (NPV) and misclassification percentage at 350 and 200 CD4 count thresholds; were also determined. Finally, because FACSPresto can also measure hemoglobin (Hb) concentration, 52 samples were used to compare FACSPresto against an automated hematology analyzer.

Results
The coefficient of determination R2 was 0.93 for both methods. Bland–Altman analysis displayed a mean bias of − 32.3 and − 8.1 cells/µl for PIMA and FACSPresto, respectively. Moreover, with a threshold of 350 CD4 count, PIMA displayed a sensitivity, specificity, PPV, NPV, were 88.57%, 94.12%, 91.18%, 92.31%; respectively. FACSPresto showed 88.23%, 96.23%, 93.75% and 92.73%; respectively. Furthermore, the upward misclassification percentage was 8.57 and 5.88%, for PIMA and FACSPresto, respectively; whereas the downward misclassification percentage was 7.84% and 7.54%; respectively. With 200 cells/µl threshold, PIMA had a sensitivity, specificity, PPV and NPV of 83.33%, 98.53%, 93.75% and 95.71%, respectively. Regarding FACSPresto, sensitivity, specificity, PPV and NPV was 82.35%, 98.57%, 88.57% and 95.83%; respectively. Upward misclassification percentage was 5.56% and 5.88%, for PIMA and FACSPresto, respectively; whereas downward misclassification percentage was 4.41% and 4.29%; respectively. Finally, the hemoglobin measurement evaluation displayed an R2 of 0.80 and a mean bias of − 0.12 with a LOA between − 1.75 and 1.51.

Conclusion
When compared to the reference method, PIMA and FACSPresto have shown good performance, for CD4 counting. The introduction of such POC technology will speed up the uptake of patients in the continuum of HIV care, in our country.
Core-labelling technique (CLT): a novel combination of the ingrowth-core method and tracer technique for deep root study
Authors: Han Eusun , Dresbøll Dorte Bodin , Thorup-Kristensen Kristian 
Published: June 2020

Abstract
Background
Ingrowth-core method is a useful tool to determine fine root growth of standing crops by inserting root-free soil in mesh-bags for certain period of time. However, the root density observed by the method does not directly explain the nutrient uptake potential of crop plants as it varies over soil depth and incubation time. We have inserted an access-tube up to 4.2 m of soil depth with openings directly under crop plants, through which ingrowth-cores containing labelled soil with nutrient tracers were installed, called core-labelling technique (CLT). The main advantage of CLT would be its capacity to determine both root density and root activity from the same crop plants in deep soil layers. We tested the validity of the new method using a model crop species, alfalfa (Medicago sativa) against three depth-levels (1.0, 2.5 and 4.2 m), three sampling spots with varying distance (0–0.36, 0.36–0.72 and > 5 m from core-labelled spot), two sampling times (week 4 and 8), and two plant parts (young and old leaves) under two field experiments (spring and autumn).

Results
Using CLT, we were able to observe both deep root growth and root activity up to 4.2 m of soil depth. Tracer concentrations revealed that there was no sign of tracer-leakage to adjacent areas which is considered to be advantageous over the generic tracer-injection. Root activity increased with longer incubation period and tracer concentrations were higher in younger leaves only for anionic tracers.

Conclusions
Our results indicate that CLT can lead to a comprehensive deep root study aiming at measuring both deep root growth and root activity from the same plants. Once produced and installed, the access-tubes and ingrowth-cores can be used for a long-term period, which reduces the workload and cost for the research. Therefore, CLT has a wide range of potential applications to the research involving roots in deep soil layers, which requires further confirmation by future experiments.