bluuebunny/crossref_metadata_2025_split huggingface dataset:
Talimogene laherparepvec upregulates immune-cell populations in non-injected lesions: findings from a phase II, multicenter, open-label study in patients with stage IIIB–IVM1c melanoma
Authors: Malvehy Josep , Samoylenko Igor , Schadendorf Dirk , Gutzmer Ralf , Grob Jean-Jacques , Sacco Joseph J , Gorski Kevin S , Anderson Abraham , Pickett Cheryl A , Liu Kate , Gogas Helen 
Published: March 2021

BackgroundTalimogene laherparepvec (T-VEC), an oncolytic virus, was designed to selectively replicate in and lyse tumor cells, releasing tumor-derived antigen to stimulate a tumor-specific immune response.MethodsIn this phase II study in patients with unresectable stage IIIB–IV melanoma, we evaluated non-injected lesions to establish whether baseline or change in intratumoral CD8+ T-cell density (determined using immunohistochemistry) correlated with T-VEC clinical response.ResultsOf 112 enrolled patients, 111 received ≥1 dose of T-VEC. After a median follow-up of 108.0 weeks, objective/complete response rates were 28%/14% in the overall population and 32%/18% in patients with stage IIIB–IVM1a disease. No unexpected toxicity occurred. Baseline and week 6 change from baseline CD8+ T-cell density results were available for 91 and 65 patients, respectively. Neither baseline nor change in CD8+ T-cell density correlated with objective response rate, changes in tumor burden, duration of response or durable response rate. However, a 2.4-fold median increase in CD8+ T-cell density in non-injected lesions from baseline to week 6 was observed. In exploratory analyses, multiparameter immunofluorescence showed that after treatment there was an increase in the proportion of infiltrating CD8+ T-cells expressing granzyme B and checkpoint markers (programmed death-1, programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte antigen-4) in non-injected lesions, together with an increase in helper T-cells. Consistent with T-cell infiltrate, we observed an increase in the adaptive resistance marker PD-L1 in non-injected lesions.ConclusionsThis study indicates that T-VEC induces systemic immune activity and alters the tumor microenvironment in a way that will likely enhance the effects of other immunotherapy agents in combination therapy.Trial registration numberNCT02366195.
Aspirin treatment prevents inflammation in experimental bifurcation aneurysms in New Zealand White rabbits
Authors: Wanderer Stefan , Grüter Basil Erwin , Strange Fabio , Boillat Gwendoline , Sivanrupan Sivani , Rey Jeannine , von Gunten Michael , Remonda Luca , Widmer Hans Rudolf , Casoni Daniela , Andereggen Lukas , Fandino Javier , Marbacher Serge 
Published: March 2021

BackgroundAneurysm wall degeneration is linked to growth and rupture. To address the effect of aspirin (ASA) on aneurysm formation under various wall conditions, this issue was analyzed in a novel rabbit bifurcation model.MethodsBifurcation aneurysms created in 45 New Zealand White rabbits were randomized to vital (n=15), decellularized (n=13), or elastase-degraded (n=17) wall groups; each group was assigned to a study arm with or without ASA. At follow-up 28 days later, aneurysms were evaluated for patency, growth, and wall inflammation at macroscopic and histological levels.Results36 rabbits survived to follow-up at the end of the trial. None of the aneurysms had ruptured. Patency was visualized in all aneurysms by intraoperative fluorescence angiography and confirmed in 33 (92%) of 36 aneurysms by MRI/MRA. Aneurysm size was significantly increased in the vital (without ASA) and elastase-degraded (with and without ASA) groups. Aneurysm thrombosis was considered complete in three (50%) of six decellularized aneurysms without ASA by MRI/MRA. Locoregional inflammation of the aneurysm complex was significantly reduced in histological analysis among all groups treated with ASA.ConclusionASA intake prevented inflammation of both the periadventitial tissue and aneurysm wall, irrespective of initial wall condition. Although ASA prevented significant growth in aneurysms with vital walls, this preventive effect did not have an important role in elastase-degraded pouches. In possible translation to the clinical situation, ASA might exert a potential preventive effect during early phases of aneurysm formation in patients with healthy vessels but not in those with highly degenerative aneurysm walls.
The local-filament pattern in the anomalous transparency of the Universe for energetic gamma rays
Authors: Troitsky Sergey 
Published: March 2021

AbstractThe propagation length of high-energy photons through the Universe is limited by$$e^{+}e^{-}$$e+e-pair production on the extragalactic background radiation. Previous studies reported discrepancies between predicted and observed attenuation, suggesting explanations in terms of new physics. However, these effects are dominated by a limited number of observed sources, while many do not show any discrepancy. Here, we consider the distribution in the sky of these apparently anomalous objects, selected in two very different approaches: the study of unphysical hardenings at distance-dependent energies in deabsorbed spectra of TeV blazars, and the observation of ultra-high-energy air showers from the directions of BL Lac type objects. In both cases, directions to the anomalous sources follow the projected local distribution of galaxies: all the distant sources, contributing to the anomalies, are seen through the local filament. This matches the prediction of the proposed earlier explanation of the anomalies based on mixing of photons with axion-like particles in the filament’s magnetic field. For ultra-high energies, this axion interpretation may be tested by the search of primary gamma rays.
Theoretical study of the $$D^0 \rightarrow K^- \pi ^+ \eta $$ reaction
Authors: Toledo Genaro , Ikeno Natsumi , Oset Eulogio 
Published: March 2021

AbstractWe develop a model to study the $$D^0 \rightarrow K^- \pi ^+ \eta $$

D
0

→

K
-

π
+

η

weak decay, starting with the color favored external emission and Cabibbo favored mode at the quark level. A less favored internal emission decay mode is also studied as a source of small corrections. Some pairs of quarks are allowed to hadronize producing two pseudoscalar mesons, which posteriorly are allowed to interact to finally provide the $$K^- \pi ^+ \eta $$

K
-

π
+

η

state. The chiral unitary approach is used to take into account the final state interaction of pairs of mesons, which has as a consequence the production of the $$\kappa $$
κ
($$K^*_0(700)$$

K
0
∗

(
700
)

) and the $$a_0(980)$$

a
0

(
980
)

resonances, well visible in the invariant mass distributions. We also introduce the $$\bar{K}^{*0} \eta $$

K

¯

∗
0

η

production in a phenomenological way and show that the s-wave pseudoscalar interaction together with this vector excitation mode are sufficient to provide a fair reproduction of the experimental data. The model provides the relative weight of the $$a_0(980)$$

a
0

(
980
)

to the $$\kappa $$
κ
excitation, and their strength is clearly visible in the low energy part of the $$K \pi $$

K
π

spectrum.
First record of the leafhopper tribe Adelungiini Baker (Hemiptera, Auchenorrhyncha, Cicadellidae: Megophthalminae) from Turkey, with notes on Achrus albicosta (Kusnezov, 1929)
Authors: GNEZDILOV VLADIMIR M. , ÖZGEN INANÇ , EMELJANOV ALEXANDR F. , NEIMOROVETS VLADIMIR V. 
Published: March 2021

The tribe Adelungiini Baker, 1915 is recorded for the first time from Turkey and the genus Achrus Lindberg, 1925 is recorded for the first time from China based on Achrus albicosta (Kusnezov, 1929) collected by Kozlov’s Mongol-Sichuan expedition in Inner Mongolia at the beginning of last century and recently—in Eastern Anatolia, Elaziğ Province. New locality records as well as illustrations of external view and male genitalia structures for A. albicosta are given from Mongolia, Kazakhstan, Turkmenistan, Uzbekistan, and Iran.
What Ails India’s Electronic Manufacturing Industry: An Assessment
Authors: Raju Sunitha , Saradhi V. Raveendra 
Published: March 2021

Manufacturing imperatives of the electronics industry require technological capability across components to develop a strong supply base. With domestic value addition being less than 25%, catapulting domestic production capability would necessitate promoting productivity enhancing innovations at the firm level, particularly in design and development capabilities. For assessing the technological orientation of the electronics manufacturing Industry, the empirical investigation of this article focuses on two important channels of influence, namely imports and firm productivity and exports and firm productivity under a liberalised regime, thereby identifying the determinants of production growth of electronics manufacturing in India. The econometric analysis has underlined the low technological capability of manufacturing firms. While the import of raw material is significant for both domestic-oriented and export-oriented firms, import of capital goods is significant for only export-oriented firms. Further, R&D expenditure is low which is statistically significant. Taken together, these results highlight that high imports are on account of domestic non-availability, and imports have substituted domestic R&D that underlines low technological capability of Indian firms. Further, export-oriented firms have technologically advanced products possibly to face the competitive pressures in the international market. To supplement these insights, the descriptive analysis focused on the trade orientation of the sample firms and cost structure in determining their market behaviour. The share of firms engaging in domestic activity surged post liberalisation, suggesting that the focus was primarily on fast expanding domestic market. As such, import engagement has increased significantly but export engagement has decreased. This suggests that imports have not facilitated export growth but only bridged the gap of non-availability of inputs domestically. The analysis of cost structure points to a decline in the share of capital goods and R&D, both implying lack of technological capability of the firms. Further, increasingly firms are turning to trading, that is, import of finished goods. As such, to promote a conducive manufacturing ecosystem, there is a need to promote technological capability and encourage export orientation of the firms. JEL Codes: F10, F14, L63
Extraction of Aural Foreign Bodies in a Rural Setting: 10-Year Review and a Novel Method to Remove Magnetic Stones
Authors: Reyes-Chicuellar Nayellin , Crossland Graeme 
Published: March 2021

Background: The external auditory canal’s unique anatomical characteristics made the presence of foreign bodies (FBs) a clinical challenge, particularly in rural settings without ready access to tertiary care and specialist intervention. Aims: Our study surveys the experience in aural FBs surgical management in a rural Australian tertiary center. It proposes a safe, easy, and affordable technique to remove stones from the ear canal. Methods: We have completed a 10-year retrospective surgical chart review, including 474 patients (52 adults and 428 children) requiring surgical management to remove aural FBs at the Royal Darwin Hospital, Northern Territory, Australia. We surveyed for patient demographics, foreign-body description, complications, location, and removal attempts. We identified what factors determine the need for surgical management and propose a technique for a safe, uncomplicated, and affordable removal of stones from the ear canal after applying this method in a small subgroup. Results: The most common FBs requiring surgery in children were stones. A predominance in the Aboriginal population from remote communities was found, leading to a nasal bridle magnet technique to remove stones in rural settings. This method reduces the number of extraction attempts of the most frequent FB found in children’s ears, aiming to minimize complications, negative experiences, and health cost. Conclusion: Contrary to international literature, stones were found to be the most common FB in remote aboriginal populations. The proposed technique reduces the number of extraction attempts of the most frequent FB found in children’s ears, aiming to minimize complications, negative experiences, and health cost.
Dietary guidelines training may improve health promotion practice: Results of a controlled trial in Brazil
Authors: Tramontt Cláudia Raulino , Maia Tarsis de Mattos , Baraldi Larissa Galastri , Jaime Patricia Constante 
Published: March 2021

Background: The double burden of malnutrition points to an urgent need to develop strategies to promote healthy diets. Health professionals are key elements for health promotion and must be prepared to deal with these issues in health services. Aim: This study aimed to evaluate the impact of an educational intervention based on Brazilian Dietary Guidelines in the practice of multidisciplinary teams working in primary health care. Methods: A controlled trial comprising pre- and post-tests was conducted with four multidisciplinary healthcare teams. The intervention group received 16 hours of training on the Brazilian Dietary Guidelines. The professionals’ practices were evaluated by direct observation, before and after the intervention, for two months at each timepoint. Data on dietary counselling were collected using a previously validated scale. The Kruskal-Wallis test was used for intragroup comparison at T0 versus T1, and the intergroup effects of the intervention were estimated by generalized linear regression analysis with a 95% confidence interval. Results: The regression with the interaction term between the intervention group and time showed a positive effect of the educational intervention on professionals’ practices in the intervention group in the crude and adjusted models (coefficient = 1.36 and p = 0.020). Brazilian Dietary Guidelines application significantly increased in non-nutritionist professionals’ practices ( p = 0.007) and in activities not related to nutrition ( p = 0.028) in the intervention group over time (T1-T0). No significant differences were found in the control group. Conclusion: The intervention proved to be effective in promoting changes in health professionals’ practices, demonstrating the strength of the strategy for dissemination of nutrition guidelines in primary health care.
A comparison between laterally wedged insoles and ankle-foot orthoses for the treatment of medial osteoarthritis of the knee: A randomized cross-over trial
Authors: Schwarze Martin , Bartsch Leonie P , Block Julia , Alimusaj Merkur , Jaber Ayham , Schiltenwolf Marcus , Wolf Sebastian I 
Published: March 2021

Objective: To compare biomechanical and clinical outcome of laterally wedged insoles (LWI) and an ankle-foot orthosis (AFO) in patients with medial knee osteoarthritis. Design: Single-centre, block-randomized, cross-over controlled trial. Setting: Outpatient clinic. Subjects: About 39 patients with symptomatic medial knee osteoarthritis. Interventions: Patients started with either LWI or AFO, determined randomly, and six weeks later changed to the alternative. Main measures: Change in the 1st maximum of external knee adduction moment (eKAM) was assessed with gait analysis. Additional outcomes were other kinetic and kinematic changes and the patient-reported outcomes EQ-5D-5L, Oxford Knee Score (OKS), American Knee Society Clinical Rating System (AKSS), Hannover Functional Ability Questionnaire – Osteoarthritis and knee pain. Results: Mean age (SD) of the study population was 58 (8) years, mean BMI 30 (5). Both aids significantly improved OKS (LWI P = 0.003, AFO P = 0.001), AKSS Knee Score (LWI P = 0.01, AFO P = 0.004) and EQ-5D-5L Index (LWI P = 0.001, AFO P = 0.002). AFO reduced the 1st maximum of eKAM by 18% ( P < 0.001). The LWI reduced both maxima by 6% ( P = 0.02, P = 0.03). Both AFO and LWI reduced the knee adduction angular impulse (KAAI) by 11% ( P < 0.001) and 5% ( P = 0.05) respectively. The eKAM (1st maximum) and KAAI reduction was significantly larger with AFO than with LWI ( P = 0.001, P = 0.004). Conclusions: AFO reduces medial knee load more than LWI. Nevertheless, no clinical superiority of either of the two aids could be shown.
A qualitative and quantitative account of patient’s experiences of ketamine and its antidepressant properties
Authors: Sumner Rachael L , Chacko Emme , McMillan Rebecca , Spriggs Meg J , Anderson Christie , Chen James , French Amelia , Jung SungHun , Rajan Akshaya , Malpas Gemma , Hay John , Ponton Rhys , Muthukumaraswamy Suresh D , Sundram Frederick 
Published: March 2021

Background: Ketamine is central to one of the most rapidly growing areas of neuroscientific research into novel treatments for depression. Limited research has indicated that the psychedelic properties of ketamine may play a role in its antidepressant effects. Aim: The aim of the current study was to explore the psychedelic experiences and sustained impact of ketamine in major depressive disorder. Methods: In the current study, ketamine (0.44 mg/kg) was administered to 32 volunteers with major depressive disorder in a crossover design with the active-placebo remifentanil, in a magnetic resonance imaging (MRI) environment. The 11-dimension altered states of consciousness questionnaire and individual qualitative interviews were used to capture the acute psychedelic experience. The Montgomery-Asberg Depression Rating Scale and further interviewing explored lasting effects. The second qualitative interview took place ⩾3 weeks post-ketamine. Results: Greater antidepressant response (reduction in Montgomery-Asberg Depression Rating Scale at 24 h) correlated with the 11-dimension altered states of consciousness dimensions: spirituality, experience of unity, and insight. The first qualitative interview revealed that all participants experienced perceptual changes. Additional themes emerged including loss of control and emotional and mood changes. The final interview showed evidence of a psychedelic afterglow, and changes to perspective on life, people, and problems, as well as changes to how participants felt about their depression and treatments. Conclusions: The current study provides preliminary evidence for a role of the psychedelic experience and afterglow in ketamine’s antidepressant properties. Reflexive thematic analysis provided a wealth of information on participants’ experience of the study and demonstrated the psychedelic properties of ketamine are not fully captured by commonly used questionnaires.
Shared Decision Making during the COVID-19 Pandemic
Authors: Köther Anja K. , Siebenhaar Katharina U. , Alpers Georg W. 
Published: March 2021

Objective The COVID-19 pandemic pushed some of the most well-developed health care systems to their limits. In many cases, this has challenged patient-centered care. We set out to examine individuals’ attitudes toward shared decision making (SDM) and to identify predictors of participation preference during the pandemic. Methods We conducted an online survey with a large convenience sample ( N = 1061). Our main measures of interest were participants’ generic and COVID-19–related participation preference as well as their acceptance and distress regarding a triage vignette. We also assessed anxiety, e-health literacy, and aspects of participants’ health. We conducted group comparisons and multiple linear regression analyses on participation preference as well as triage acceptance. Results In generic decision making, most participants expressed a strong need for information and a moderate participation preference. In the hypothetical case of COVID-19 infection, most preferred physician-led decisions. Generic participation preference was the strongest predictor of COVID-19–related participation preference, followed by age, education, and anxiety. Furthermore, both higher generic and COVID-19–related participation preferences predicted lower triage acceptance. Conclusion Our findings demonstrate potential health care recipients’ attitudes toward SDM during a severe health care crisis and emphasize that participation preference varies according to the context.
Clinical Evaluation of Bone-Anchored Intraoral Bodily Molar Distalizer
Authors: Sesham Vasu Murthy , Garipelli Naveen , Neela Praveen Kumar , Mamillapalli Pavan Kumar 
Published: March 2021

Introduction: Correction of Class II has become a routine with the introduction of mini-implants. Objective: The objective of the study was to evaluate the clinical efficiency of bone-anchored intraoral bodily molar distalizer (BAIBMD) as compared to bone-anchored pendulum appliance (BAPA). Materials and Methods: This split-mouth study included 11 subjects (6 boys and 5 girls) who required molar distalization. BAPA constructed on one side and BAIBMD on the other side. Both the appliances were anchored to the bone, using a single 2 × 8 mm titanium mini-screw placed in the anterior para-median region of the mid-palatal suture with its head embedded into the Nance button during construction. The force delivery mechanism on both the sides consisted of 200 g-force application, using an activated 0.032˝ titanium molybdenum alloy (TMA)[A]:Author: Please provide expansion for “TMA.” springs fabricated with respective designs and inserted into the lingual sheaths of the first molar bands. The rate, duration, and nature of tooth movement for both the sides were compared. Descriptive statistics for various parameters were analyzed using Wilcoxon signed-rank test. Results: Clinically successful distalization was achieved on both sides. No statistical difference was found in the rate of distalization. Differences in the treatment duration between the two groups were statistically significant, with less duration taken for distalization with BAPA. Statistically significant molar tipping was observed in BAPA. Conclusion: While both the appliances provided a similar rate of distalization, BAIBMD took more duration than BAPA but produced a predominantly translatory type of distal tooth movement.
Perioperative and oncological outcomes of renal cell carcinoma with venous tumour thrombus
Authors: Bokka Sriharsha , Manikandan Ramanitharan , Dorairajan Lalgudi Narayanan , Srivathsa K , Sreenivasan Sreerag Kodakkattil , Kalra Sidhartha , Pottakat Biju 
Published: March 2021

Aim: The aim of the present study is to report the perioperative and long-term surgical outcomes of renal cell carcinoma (RCC) with venous tumour thrombus (VTT). Materials and methods: Data of 34 patients (males = 23, females = 11) from 2009 to 2020 who underwent radical nephrectomy with thrombectomy for RCC and VTT was retrospectively analysed. The parameters recorded include tumour laterality, size, level of thrombus, surgical approach, blood loss, transfusion rates, operative time, hospital stay, Clavien complications, tumour histology, follow-up duration, local recurrence, distant metastasis, overall and cancer-specific survival rates. Results: The extent of thrombus was level I in thirteen, level II in twelve, level III (a-1, b-2, c-1, d-2) in six and level IV in three patients respectively. Mean operative time was 320 (±145) min, mean blood loss was 1371.15 (±1020.8) ml and mean hospital stay was 9.6 (±7.4) days. Mean transfusion rate was 6.4 (±3.2) units. Three patients died within the first 30 days of surgery. Cardiopulmonary bypass (CPB) was utilized in three patients. Median follow-up period was 58 (Range: 4–101) months. A statistically significant correlation was found between operative time ( p = 0.014) and median survival ( p = 0.003) respectively and tumour thrombosis level. Nine patients died due to metastasis, and ten due to unrelated causes. The estimated actuarial survival rates at a median of 58 months were 35.3%. Conclusion: An accurate preoperative assessment of the thrombus extent with the involvement of a multidisciplinary team approach is crucial in achieving optimal surgical outcomes in patients of RCC with VTT, particularly with level III and IV thrombus.