bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of denosumab on pedicle screw fixation: a prospective 2-year longitudinal study using finite element analysis
Authors: Tani Soji , Ishikawa Koji , Kudo Yoshifumi , Tsuchiya Koki , Matsuoka Akira , Maruyama Hiroshi , Emori Haruka , Yamamura Ryo , Hayakawa Chikara , Sekimizu Masaya , Oshita Yusuke , Ozawa Tomoyuki , Shirahata Toshiyuki , Nagai Takashi , Toyone Tomoaki , Inagaki Katsunori
Published: March 2021

Background

Pedicle screw loosening is a major complication following spinal fixation associated with osteoporosis in elderly. However, denosumab is a promising treatment in patients with osteoporosis. The effect of denosumab on pedicle screw fixation is unknown. Therefore, we investigated whether denosumab treatment improves pedicle screw fixation in elderly patients with osteoporosis.

Methods

This was a 2-year prospective open-label study. From February 2015 to January 2016, we included 21 patients with postmenopausal osteoporosis who received initial denosumab treatment. At baseline, 12 months, and 24 months, we measured volumetric bone mineral density (BMD) using quantitative computed tomography (QCT) and performed CT-based finite element analysis (FEA). Finite element models of L4 vertebrae were created to analyze the bone strength and screw fixation.

Results

BMD increased with denosumab treatment. FEA revealed that both pullout strength of pedicle screws and compression force of the vertebra increased significantly at 12 and 24 months following denosumab treatment. Notably, pullout strength showed a stronger correlation with three-dimensional volumetric BMD around pedicle screw placement assessed by QCT (r = 0.83, at 24 months) than with two-dimensional areal BMD assessed by dual energy X-ray absorptiometry (r = 0.35, at 24 months).

Conclusion

To our knowledge, this is the first study to reveal that denosumab treatment achieved strong pedicle screw fixation with an increase in BMD around the screw assessed by QCT and FEA; therefore, denosumab could be useful for osteoporosis treatment during spinal surgery in elderly patients with osteoporosis.
Is there a renoprotective value to leukodepletion during heart valve surgery? A randomized controlled trial (ROLO)
Authors: Khoshbin Espeed , Spencer Sally , Solomon Laurence , Tang Augustine , Clark Stephen , Stokes Elizabeth , Wordsworth Sarah , Dabner Lucy , Edwards Julia , Reeves Barnaby , Rogers Chris
Published: March 2021

Background

Acute Kidney Injury (AKI) adversely affects outcomes after cardiac surgery. A major mediator of AKI is the activation of leukocytes through exposure to the cardiopulmonary bypass circuit. We evaluate the use of leukodepletion filters throughout bypass to protect against post-operative AKI by removing activated leukocytes during cardiac surgery.

Methods

This is a single-centre, double-blind, randomized controlled trial comparing the use of leukodepletion versus a standard arterial filter throughout bypass. Elective adult patients undergoing heart valve surgery with or without concomitant procedures were investigated. The primary clinical outcome measured was the development of AKI according to the KDIGO criteria. Secondary measures included biomarkers of renal tubular damage (urinary Retinol Binding Protein and Kidney Injury Molecule-1), glomerular kidney injury (urinary Micro Albumin and serum Cystatin C) and urinary Neutrophil Gelatinase Associated Lipocalin, as well as the length of hospital stay and quality of life measures through EQ-5D-5L questionnaires.

Results

The ROLO trial randomized 64 participants with a rate of recruitment higher than anticipated (57% achieved, 40% anticipated). The incidence of AKI was greater in the leukodepletion filter group (44% versus 23%, risk difference 21, 95% CI − 2 to 44%). This clinical finding was supported by biomarker levels especially by a tendency toward glomerular insult at 48 h, demonstrated by a raised serum Cystatin C (mean difference 0.11, 95% CI 0.00 to 0.23,p = 0.068) in the leukodepleted group. There was however no clear association between the incidence or severity of AKI and length of hospital stay. On average, health related quality of life returned to pre-operative levels in both groups within 3 months of surgery.

Conclusions

Leukocyte depletion during cardiopulmonary bypass does not significantly reduce the incidence of AKI after valvular heart surgery. Other methods to ameliorate renal dysfunction after cardiac surgery need to be investigated.

Trial registration

The trial was registered by the International Standard Randomized Controlled Trial Number RegistryISRCTN42121335. Registered on the 18 February 2014. The trial was run by the Bristol Clinical Trials and Evaluation Unit. This trial was financially supported by the National Institute of Health Research (Research for Patient Benefit), award ID: PB-PG-0711-25,090.
High-dose rapamycin exerts a temporary impact on T. reesei RUT-C30 through gene trFKBP12
Authors: Pang Ai-Ping , Wang Haiyan , Zhang Funing , Hu Xin , Wu Fu-Gen , Zhou Zhihua , Wang Wei , Lu Zuhong , Lin Fengming
Published: March 2021

Background

Knowledge with respect to regulatory systems for cellulase production is prerequisite for exploitation of such regulatory networks to increase cellulase production, improve fermentation efficiency and reduce the relevant production cost. The target of rapamycin (TOR) signaling pathway is considered as a central signaling hub coordinating eukaryotic cell growth and metabolism with environmental inputs. However, how and to what extent the TOR signaling pathway and rapamycin are involved in cellulase production remain elusive.

Result

At the early fermentation stage, high-dose rapamycin (100 μM) caused a temporary inhibition effect on cellulase production, cell growth and sporulation of Trichoderma reesei RUT-C30 independently of the carbon sources, and specifically caused a tentative morphology defect in RUT-C30 grown on cellulose. On the contrary, the lipid content of T. reesei RUT-C30 was not affected by rapamycin. Accordingly, the transcriptional levels of genes involved in the cellulase production were downregulated notably with the addition of rapamycin. Although the mRNA levels of the putative rapamycin receptor trFKBP12 was upregulated significantly by rapamycin, gene trTOR (the downstream effector of the rapamycin–FKBP12 complex) and genes associated with the TOR signaling pathways were not changed markedly. With the deletion of gene trFKBP12, there is no impact of rapamycin on cellulase production, indicating that trFKBP12 mediates the observed temporary inhibition effect of rapamycin.

Conclusion

Our study shows for the first time that only high-concentration rapamycin induced a transient impact on T. reesei RUT-C30 at its early cultivation stage, demonstrating T. reesei RUT-C30 is highly resistant to rapamycin, probably due to that trTOR and its related signaling pathways were not that sensitive to rapamycin. This temporary influence of rapamycin was facilitated by gene trFKBP12. These findings add to our knowledge on the roles of rapamycin and the TOR signaling pathways play in T. reesei.
OncoGEMINI: software for investigating tumor variants from multiple biopsies with integrated cancer annotations
Authors: Nicholas Thomas J. , Cormier Michael J. , Huang Xiaomeng , Qiao Yi , Marth Gabor T. , Quinlan Aaron R.
Published: March 2021

Background

DNA sequencing has unveiled extensive tumor heterogeneity in several different cancer types, with many exhibiting diverse subclonal populations. Identifying and tracing mutations throughout the expansion and progression of a tumor represents a significant challenge. Furthermore, prioritizing the subset of such mutations most likely to contribute to tumor evolution or that could serve as potential therapeutic targets represents an ongoing problem.

Results

Here, we describe OncoGEMINI, a new tool designed for exploring the complex patterns and trajectory of somatic and inherited variation observed in heterogeneous tumors biopsied over the course of treatment. This is accomplished by creating a searchable database of variants that includes tumor sampling time points and allows for filtering methods that reflect specific changes in variant allele frequencies over time. Additionally, by incorporating existing annotations and resources that facilitate the interpretation of cancer mutations (e.g., CIViC, DGIdb), OncoGEMINI enables rapid searches for, and potential identification of, mutations that may be driving subclonal evolution.

Conclusions

By combining relevant genomic annotations alongside specific filtering tools, OncoGEMINI provides powerful and customizable approaches that enable the quick identification of individual tumor variants that meet specified criteria. It can be applied to a wide range of tumor-derived sequence data, but is especially designed for studies with multiple samples, including longitudinal datasets. It is available under an MIT license at github.com/fakedrtom/oncogemini.
Development of double-positive thymocytes at single-cell resolution
Authors: Li Young , Li Kun , Zhu Lianbang , Li Bin , Zong Dandan , Cai Pengfei , Jiang Chen , Du Pengcheng , Lin Jun , Qu Kun
Published: March 2021

Background

T cells generated from thymopoiesis are essential for the immune system, and recent single-cell studies have contributed to our understanding of the development of thymocytes at the genetic and epigenetic levels. However, the development of double-positive (DP) T cells, which comprise the majority of thymocytes, has not been well investigated.

Methods

We applied single-cell sequencing to mouse thymocytes and analyzed the transcriptome data using Seurat. By applying unsupervised clustering, we defined thymocyte subtypes and validated DP cell subtypes by flow cytometry. We classified the cell cycle phases of each cell according to expression of cell cycle phase-specific genes. For immune synapse detection, we used immunofluorescent staining and ImageStream-based flow cytometry. We studied and integrated human thymocyte data to verify the conservation of our findings and also performed cross-species comparisons to examine species-specific gene regulation.

Results

We classified blast, rearrangement, and selection subtypes of DP thymocytes and used the surface markers CD2 and Ly6d to identify these subtypes by flow cytometry. Based on this new classification, we found that the proliferation of blast DP cells is quite different from that of double-positive cells and other cell types, which tend to exit the cell cycle after a single round. At the DP cell selection stage, we observed that CD8-associated immune synapses formed between thymocytes, indicating that CD8sp selection occurred among thymocytes themselves. Moreover, cross-species comparison revealed species-specific transcription factors (TFs) that contribute to the transcriptional differences of thymocytes from humans and mice.

Conclusions

Our study classified DP thymocyte subtypes of different developmental stages and provided new insight into the development of DP thymocytes at single-cell resolution, furthering our knowledge of the fundamental immunological process of thymopoiesis.
Microglial PGC-1α protects against ischemic brain injury by suppressing neuroinflammation
Authors: Han Bin , Jiang Wei , Cui Pan , Zheng Kai , Dang Chun , Wang Junjie , Li He , Chen Lin , Zhang Rongxin , Wang Qing Mei , Ju Zhenyu , Hao Junwei
Published: March 2021

Background

Neuroinflammation and immune responses occurring minutes to hours after stroke are associated with brain injury after acute ischemic stroke (AIS). PPARγ coactivator-1α (PGC-1α), as a master coregulator of gene expression in mitochondrial biogenesis, was found to be transiently upregulated in microglia after AIS. However, the role of microglial PGC-1α in poststroke immune modulation remains unknown.

Methods

PGC-1α expression in microglia from human and mouse brain samples following ischemic stroke was first determined. Subsequently, we employed transgenic mice with microglia-specific overexpression of PGC-1α for middle cerebral artery occlusion (MCAO). The morphology and gene expression profile of microglia with PGC-1α overexpression were evaluated. Downstream inflammatory cytokine production and NLRP3 activation were also determined. ChIP-Seq analysis was performed to detect PGC-1α-binding sites in microglia. Autophagic and mitophagic activity was further monitored by immunofluorescence staining. Unc-51-like autophagy activating kinase 1 (ULK1) expression was evaluated under the PGC-1α interaction with ERRα. Finally, pharmacological inhibition and genomic knockdown of ULK1 were performed to estimate the role of ULK1 in mediating mitophagic activity after ischemic stroke.

Results

PGC-1α expression was shortly increased after ischemic stroke, not only in human brain samples but also in mouse brain samples. Microglia-specific PGC-1α overexpressing mice exhibited significantly decreased neurologic deficits after ischemic injury, with reduced NLRP3 activation and proinflammatory cytokine production. ChIP-Seq analysis and KEGG pathway analysis revealed that mitophagy was significantly enhanced. PGC-1α significantly promoted autophagic flux and induced autolysosome formation. More specifically, the autophagic clearance of mitochondria was enhanced by PGC-1α regulation, indicating the important role of mitophagy. Pharmacological inhibition or knockdown of ULK1 expression impaired autophagic/mitophagic activity, thus abolishing the neuroprotective effects of PGC-1α.

Conclusions

Mechanistically, in AIS, PGC-1α promotes autophagy and mitophagy through ULK1 and reduces NLRP3 activation. Our findings indicate that microglial PGC-1α may be a promising therapeutic target for AIS.
Phenome-wide investigation of the causal associations between childhood BMI and adult trait outcomes: a two-sample Mendelian randomization study
Authors: Dong Shan-Shan , Zhang Kun , Guo Yan , Ding Jing-Miao , Rong Yu , Feng Jun-Cheng , Yao Shi , Hao Ruo-Han , Jiang Feng , Chen Jia-Bin , Wu Hao , Chen Xiao-Feng , Yang Tie-Lin
Published: March 2021

Background

Childhood obesity is reported to be associated with the risk of many diseases in adulthood. However, observational studies cannot fully account for confounding factors. We aimed to systematically assess the causal associations between childhood body mass index (BMI) and various adult traits/diseases using two-sample Mendelian randomization (MR).

Methods

After data filtering, 263 adult traits genetically correlated with childhood BMI (P < 0.05) were subjected to MR analyses. Inverse-variance weighted, MR-Egger, weighted median, and weighted mode methods were used to estimate the causal effects. Multivariable MR analysis was performed to test whether the effects of childhood BMI on adult traits are independent from adult BMI.

Results

We identified potential causal effects of childhood obesity on 60 adult traits (27 disease-related traits, 27 lifestyle factors, and 6 other traits). Higher childhood BMI was associated with a reduced overall health rating (β = − 0.10, 95% CI − 0.13 to − 0.07,P = 6.26 × 10−11). Specifically, higher childhood BMI was associated with increased odds of coronary artery disease (OR = 1.09, 95% CI 1.06 to 1.11,P = 4.28 × 10−11), essential hypertension (OR = 1.12, 95% CI 1.08 to 1.16,P = 1.27 × 10−11), type 2 diabetes (OR = 1.36, 95% CI 1.30 to 1.43,P = 1.57 × 10−34), and arthrosis (OR = 1.09, 95% CI 1.06 to 1.12,P = 8.80 × 10−9). However, after accounting for adult BMI, the detrimental effects of childhood BMI on disease-related traits were no longer present (P > 0.05). For dietary habits, different from conventional understanding, we found that higher childhood BMI was associated with low calorie density food intake. However, this association might be specific to the UK Biobank population.

Conclusions

In summary, we provided a phenome-wide view of the effects of childhood BMI on adult traits. Multivariable MR analysis suggested that the associations between childhood BMI and increased risks of diseases in adulthood are likely attributed to individuals remaining obese in later life. Therefore, ensuring that childhood obesity does not persist into later life might be useful for reducing the detrimental effects of childhood obesity on adult diseases.
Retraction Note: Assessment of healthiness among long term inhabiting army soldiers in dry zone of Sri Lanka
Authors: Jayaweera Jayaweera Arachchige Asela Sampath , Joseph Anpalaham
Published: March 2021

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s13104-021-05537-4
Diet and gut microbiome interactions of relevance for symptoms in irritable bowel syndrome
Authors: Tap Julien , Störsrud Stine , Le Nevé Boris , Cotillard Aurélie , Pons Nicolas , Doré Joël , Öhman Lena , Törnblom Hans , Derrien Muriel , Simrén Magnus
Published: March 2021

Background

While several studies have documented associations between dietary habits and microbiota composition and function in healthy individuals, no study explored these associations in patients with irritable bowel syndrome (IBS), and especially with symptoms.

Methods

Here, we used a novel approach that combined data from a 4-day food diary, integrated into a food tree, together with gut microbiota (shotgun metagenomic) for individuals with IBS (N = 149) and healthy controls (N = 52). Paired microbiota and food-based trees allowed us to detect new associations between subspecies and diet. Combining co-inertia analysis and linear regression models, exhaled gas levels and symptom severity could be predicted from metagenomic and dietary data.

Results

We showed that individuals with severe IBS are characterized by a higher intake of poorer-quality food items during their main meals. Our analysis suggested that covariations between gut microbiota at subspecies level and diet could be explained with IBS symptom severity, exhaled gas, glycan metabolism, and meat/plant ratio. We provided evidence that IBS severity is associated with altered gut microbiota hydrogen function in correlation with microbiota enzymes involved in animal carbohydrate metabolism.

Conclusions

Our study provides an unprecedented resolution of diet-microbiota-symptom interactions and ultimately guides new interventional studies that aim to identify gut microbiome-based nutritional recommendations for the management of gastrointestinal symptoms.

Trial registration

This trial was registered on the ClinicalTrials.gov, with the registration number NCT01252550, on 3rd December 2010.
A small-molecule pan-class I glucose transporter inhibitor reduces cancer cell proliferation in vitro and tumor growth in vivo by targeting glucose-based metabolism
Authors: Shriwas Pratik , Roberts Dennis , Li Yunsheng , Wang Liyi , Qian Yanrong , Bergmeier Stephen , Hines Jennifer , Adhicary Subhodip , Nielsen Corinne , Chen Xiaozhuo
Published: March 2021

Background

Cancer cells drastically increase the uptake of glucose and glucose metabolism by overexpressing class I glucose transporters (GLUT1-4) to meet their energy and biomass synthesis needs and are very sensitive and vulnerable to glucose deprivation. Although targeting glucose uptake via GLUTs has been an attractive anticancer strategy, the relative anticancer efficacy of multi-GLUT targeting or single GLUT targeting is unclear. Here, we report DRB18, a synthetic small molecule, is a potent anticancer compound whose pan-class I GLUT inhibition is superior to single GLUT targeting.

Methods

Glucose uptake and MTT/resazurin assays were used to measure DRB18’s inhibitory activities of glucose transport and cell viability/proliferation in human lung cancer and other cancer cell lines. Four HEK293 cell lines expressing GLUT1-4 individually were used to determine the IC50values of DRB18’s inhibitory activity of glucose transport. Docking studies were performed to investigate the potential direct interaction of DRB18 with GLUT1-4. Metabolomics analysis was performed to identify metabolite changes in A549 lung cancer cells treated with DRB18. DRB18 was used to treat A549 tumor-bearing nude mice. TheGLUT1gene was knocked out to determine how the KO of the gene affected tumor growth.

Results

DRB18 reduced glucose uptake mediated via each of GLUT1-4 with different IC50s, which match with the docking glidescores with a correlation coefficient of 0.858. Metabolomics analysis revealed that DRB18 altered energy-related metabolism in A549 cells by changing the abundance of metabolites in glucose-related pathways in vitro and in vivo. DRB18 eventually led to G1/S phase arrest and increased oxidative stress and necrotic cell death. IP injection of DRB18 in A549 tumor-bearing nude mice at 10 mg/kg body weight thrice a week led to a significant reduction in the tumor volume compared with mock-treated tumors. In contrast, the knockout of theGLUT1gene did not reduce tumor volume.

Conclusions

DRB18 is a potent pan-class I GLUT inhibitor in vitro and in vivo in cancer cells. Mechanistically, it is likely to bind the outward open conformation of GLUT1-4, reducing tumor growth through inhibiting GLUT1-4-mediated glucose transport and metabolisms. Pan-class I GLUT inhibition is a better strategy than single GLUT targeting for inhibiting tumor growth.
Association of transcranial Doppler blood flow velocity slow waves with delayed cerebral ischemia in patients suffering from subarachnoid hemorrhage: a retrospective study
Authors: Papaioannou Vasilios E. , Budohoski Karol P. , Placek Michal M. , Czosnyka Zofia , Smielewski Peter , Czosnyka Marek
Published: March 2021

Background

Cerebral vasospasm (VS) and delayed cerebral ischemia (DCI) constitute major complications following subarachnoid hemorrhage (SAH). A few studies have examined the relationship between different indices of cerebrovascular dynamics with the occurrence of VS. However, their potential association with the development of DCI remains elusive. In this study, we investigated the pattern of changes of different transcranial Doppler (TCD)-derived indices of cerebrovascular dynamics during vasospasm in patients suffering from subarachnoid hemorrhage, dichotomized by the presence of delayed cerebral ischemia.

Methods

A retrospective analysis was performed using recordings from 32 SAH patients, diagnosed with VS. Patients were divided in two groups, depending on development of DCI. Magnitude of slow waves (SWs) of cerebral blood flow velocity (CBFV) was measured. Cerebral autoregulation was estimated using the moving correlation coefficient Mxa. Cerebral arterial time constant (tau) was expressed as the product of resistance and compliance. Complexity of CBFV was estimated through measurement of sample entropy (SampEn).

Results

In the whole population (N = 32), magnitude of SWs of ipsilateral to VS side CBFV was higher during vasospasm (4.15 ± 1.55 vs before: 2.86 ± 1.21 cm/s, p < 0.001). Ipsilateral SWs of CBFV before VS had higher magnitude in DCI group (N = 19, p < 0.001) and were strongly predictive of DCI, with area under the curve (AUC) = 0.745 (p = 0.02). Vasospasm caused a non-significant shortening of ipsilateral values of tau and increase in SampEn in all patients related to pre-VS measurements, as well as an insignificant increase of Mxa in DCI related to non-DCI group (N = 13).

Conclusions

In patients suffering from subarachnoid hemorrhage, TCD-detected VS was associated with higher ipsilateral CBFV SWs, related to pre-VS measurements. Higher CBFV SWs before VS were significantly predictive of delayed cerebral ischemia.
Comparison of length and dynamics of wood pieces in streams covered with coniferous and broadleaf forests mapped using orthophotos acquired by an unmanned aerial vehicle
Authors: Tsunetaka Haruka , Mtibaa Slim , Asano Shiho , Okamoto Takashi , Kurokawa Ushio
Published: March 2021

As wood pieces supplied by landslides and debris flows are one of the main components of ecological and geomorphic systems, the importance of quantifying the dimensions of the wood pieces is evident. However, the low accessibility of disturbed channels after debris flows generally impedes accurate and quick wood-piece investigations. Thus, remote-sensing measurements for wood pieces are necessitated. Focusing on sub-watersheds in coniferous and broadleaf forests in Japan (the CF and BF sites, respectively), we measured the lengths of wood pieces supplied by landslides (> 0.2 m length and > 0.03 m diameter) from orthophotos acquired using a small unmanned aerial vehicle (UAV). The measurement accuracy was analyzed by comparing the lengths derived from the UAV method with direct measurements. The landslides at the CF and BF sites were triggered by extremely heavy rainfalls in 2017 and 2018, respectively. UAV flights were operated during February and September 2019 at the CF site and during November 2018 and December 2019 at the BF site. Direct measurements of wood pieces were carried out on the date of the respective second flight date in each site. When both ends of a wood piece are satisfactorily extracted from an orthophoto acquired by the UAV, the wood-piece lengths at the CF site can be measured with an accuracy of approximately ±0.5 m. At the BF site, most of the extracted lengths were shorter than the directly measured lengths, probably because the complex structures of the root wad and tree crown reduced the visibility. Most wood pieces were discharged from landslide scars at the BF site, but at the CF site, approximately 750 wood pieces remained in the landslide scars approximately 19 months after the landslide occurrence. The number of wood pieces in the landslide scars of the CF site increased with increasing landslide area, suggesting that some wood pieces can be left even if large landslides occur. The lengths and locations of the entrapped wood pieces at both sites were not significantly changed between the two UAV flight dates. However, during this period, the rainfall intensities around the CF site measured by the closest rain-gauge of the Japan Meteorological Agency reached their second highest values from 1976 to 2019, which exceeded the 30-year return period. This suggests that most of the entrapped wood pieces rarely migrated even under intense rainfall.
Dexamethasone to decrease post-anesthesia sore throat (POST) and hoarseness-which is the most effective route: intravenous, topical, or nebulization? A prospective randomized trial
Authors: Sharma Shalini , Bhardwaj Vatika , Sharma Shailja , Rana Shelly
Published: March 2021

Background and Aims

Postoperative sore throat (POST) is common after endotracheal intubation making patients uncomfortable and anxious in postoperative period. The present study was undertaken to compare efficacy of equal dose of dexamethasone in preventing POST via three different routes, i.e., intravenous, topical, and nebulization before surgery.

Methods and Results

The present prospective double-blind randomized parallel group trial included 190 patients of either sex above 18 years, American Society of Anesthesiologists (ASA) physical status I–II posted for laparoscopic cholecystectomy. The patients were divided into three groups. Patients in group N were nebulized with 8 mg dexamethasone prior to surgery, patients in group I received intravenous dexamethasone (8 mg) before induction of anesthesia, while patients in group C were intubated with endotracheal tube which was pretreated (cuff soaked in dexamethasone 8 mg). The severity of POST and hoarseness of voice was determined by interviewing patients after 24-h of completion of surgery. Incidence of POST decreased in all patients with maximum decrease in group N (18%), while 30.8% in group I and 30.4% in group C. This decrease was not statistically significant when compared to group I (p 0.14) as well as group C (p 0.15). Incidence of hoarseness significantly decreased in group N (15.6%) as compared to group I (40.3%) as well as group C (39.1%). This decrease was statistically significant when compared to group I (p 0.005) as well as group C (p 0.009).

Conclusions

Topical dexamethasone (group C) is as effective as intravenous dexamethasone in decreasing incidence of POST, while both the techniques are not effective in decreasing hoarseness of voice. Nebulization is most effective method in decreasing POST as well as hoarseness.

Trial Registration

CTRI/2017/08/009524 dated 29 August 2017 prospectively.
A carbon nanotubes based in situ multifunctional power assist system for restoring failed heart function
Authors: Xu Quanfu , Yang Yuli , Hou Jianwen , Chen Taizhong , Fei Yudong , Wang Qian , Zhou Qing , Li Wei , Ren Jing , Li Yi-Gang
Published: March 2021

Background

End-stage heart failure is a major risk of mortality. The conductive super-aligned carbon nanotubes sheets (SA-CNTs) has been applied to restore the structure and function of injured myocardium through tissue engineering, and developed as efficient cardiac pacing electrodes. However, the interfacial interaction between SA-CNTs and the surface cells is unclear, and it remains challenge to restore the diminished contraction for a seriously damaged heart.

Results

A concept of a multifunctional power assist system (MPS) capable of multipoint pacing and contraction assisting is proposed. This device is designed to work with the host heart and does not contact blood, thus avoiding long-term anticoagulation required in current therapies. Pacing electrode constructed by SA-­CNTs promotes the epithelial-mesenchymal transition and directs the migration of pro-regenerative epicardial cells. Meanwhile, the power assist unit reveals an excellent frequency response to alternating voltage, with natural heart mimicked systolic/diastolic amplitudes. Moreover, this system exhibits an excellent pacing when attached to the surface of a rabbit heart, and presents nice biocompatibility in both in vitro and in vivo evaluation.

Conclusions

This MPS provides a promising non-blood contact strategy to restore in situ the normal blood-pumping function of a failed heart.
Artificial intelligence development for detecting prostate cancer in MRI
Authors: Aphinives Chalida , Aphinives Potchavit
Published: March 2021

Background

Artificial intelligence (AI) is the recently advanced technology in machine learning which is increasingly used to help radiologists, especially when working in arduous conditions. Microsoft Corporation offered a free-trial service calling Custom Vision to develop AI for images.

Results

This study included 161 prostate cancer images with 189 lesions from 52 patients. The 160-tag iteration presented the best performance: precision 20.0%, recall 6.3%, mean average precision (M.A.P.) 13.1%, and prediction rate 31.58%. The performance of a 1-h training was better than quick training, but was not different from a 2-h training.

Conclusion

Health personnel can easily develop AI for the detection of prostate cancer lesions in MRI. However, the AI development is further required, and the result should be interpreted along with radiologist.
Standard-Dose Osimertinib in EGFR-Mutated Non–Small-Cell Lung Adenocarcinoma With Leptomeningeal Disease
Authors: McLean Luke S. , Faisal Wasek , Parakh Sagun , Kao Steven C. , Lewis Craig R. , Chin Melvin T. , Voskoboynik Mark , Itchins Malinda J. , Jennens Ross R. , Broad Adam R. , Morris Tessa A. , Solomon Benjamin J.
Published: March 2021

PURPOSE

Leptomeningeal disease (LMD) in epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma is associated with a poor prognosis and limited treatment options. Osimertinib is a potent third-generation EGFR tyrosine kinase inhibitor with confirmed CNS penetration. This study reports on outcomes of patients with EGFR-mutated non–small-cell lung cancer who developed LMD and were subsequently treated with osimertinib.

METHODS

We identified patients treated with osimertinib 80 mg PO daily under a compassionate access scheme across nine tertiary Australian institutes between July 2017 and July 2020. Patient demographics, tumor characteristics, and treatment history were collected. Median overall survival, median progression-free survival, disease control rates (DCR), and overall response rates (ORR) were assessed. Kaplan-Meier analysis was performed and descriptive statistics were used.

RESULTS

Thirty-nine patients were analyzed of which 74% were female. Exon 19 deletions (49%) and L858R point mutations (41%) were the most common EGFR mutations. Forty-nine percentage of patients were Eastern Cooperative Oncology Group 1. The median duration of osimertinib therapy was 6 months. The extracranial DCR and ORR were 60% and 54%, and the intracranial DCR and ORR were 68% and 53%, respectively. Median overall survival was 10.5 months (95% CI, 8.17 to 15.05 months).

CONCLUSION

There are limited treatment options for LMD in EGFR-positive lung cancer, and osimertinib at a dose of 80 mg daily is an active therapeutic option for these patients.
The Treatment of Disability under Crisis Standards of Care: An Empirical and Normative Analysis of Change over Time during COVID-19
Authors: Ne'eman Ari , Stein Michael Ashley , Berger Zackary D. , Dorfman Doron
Published: March 2021

Context: COVID-19 has prompted debates between bioethicists and disability activists about Crisis Standards of Care plans (CSCs), triage protocols determining the allocation of scarce lifesaving care.

Methods: We examine CSCs in 35 states and code how they approach disability, comparing states that have revised their plans over time to those that have not. We offer ethical and legal analyses evaluating to what extent changes to state policy aligned with disability rights law and ethics during the early pandemic and subsequently as stakeholder engagement grew.

Findings: While disability rights views were not well represented in CSCs that were not updated or updated early in the pandemic, states that revised their plans later in the pandemic were more aligned with advocate priorities. However, many CSCs continue to include concerning provisions, especially the reliance on long-term survival, which implicates considerations of both disability rights and racial justice.

Conclusions: The disability rights movement's successes in influencing state triage policy should inform future CSCs and set the stage for further work on how stakeholders influence bioethics policy debates. We offer thoughts for examining bioethics policy making reflecting the processes by which activists seek policy change and the tension policy makers face between expert delegation and mediating values conflicts.
Americans' View of the Impact of COVID-19: Perspectives on Racial Impacts and Equity
Authors: Carman Katherine , Chandra Anita , Miller Carolyn , Nelson Christopher , Williams Jhacova
Published: March 2021

Context: The COVID-19 pandemic has had a disparate effect on African Americans and Latinos. But it is unknown how aware the public is of these differences and how the pandemic has changed perceptions of equity and access to health care.

Methods: We use panel data from nationally representative surveys fielded to the same respondents in 2018 and 2020 to assess views and changes in views over time.

Findings: We found that awareness of inequity is highest among Non-Hispanic Black respondents and higher-income and higher-educated groups, and there have been only small changes in perceptions of inequity over time. However, there have been significant changes in views of the government's obligation to ensure access to health care.

Conclusions: Even in the face of a deadly pandemic, one that has killed disproportionately more African Americans and Latinos, many in the United States continue not to recognize that there are inequities in access to health care and the impact of COVID-19 on certain groups. But policies to address inequity may be shifting. We will continue to follow these respondents to see whether changes in attitudes endure over time or dissipate.
Performance of deep learning models constructed using panoramic radiographs from two hospitals to diagnose fractures of the mandibular condyle
Authors: Nishiyama Masako , Ishibashi Kenichiro , Ariji Yoshiko , Fukuda Motoki , Nishiyama Wataru , Umemura Masahiro , Katsumata Akitoshi , Fujita Hiroshi , Ariji Eiichiro
Published: March 2021

Objective:

The present study aimed to verify the classification performance of deep learning (DL) models for diagnosing fractures of the mandibular condyle on panoramic radiographs using data sets from two hospitals and to compare their internal and external validities.

Methods:

Panoramic radiographs of 100 condyles with and without fractures were collected from two hospitals and a fivefold cross-validation method was employed to construct and evaluate the DL models. The internal and external validities of classification performance were evaluated as accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC).

Results:

For internal validity, high classification performance was obtained, with AUC values of >0.85. Conversely, external validity for the data sets from the two hospitals exhibited low performance. Using combined data sets from both hospitals, the DL model exhibited high performance, which was slightly superior or equal to that of the internal validity but without a statistically significant difference.

Conclusion:

The constructed DL model can be clinically employed for diagnosing fractures of the mandibular condyle using panoramic radiographs. However, the domain shift phenomenon should be considered when generalizing DL systems.
Communications ’ Efects on Politics and Social Change: A Study on Harold A. Innis
Authors: Oruç Mehmet Sebih
Published: March 2021

The importance of communications on social change increasingly recognized in both academic and popular works. Te effect and presence of communications are felt in all aspects of human life and these tools are usually considered to have signifcant effects on human activities in the social, political and cultural spheres. Harold A. Innis is one of the frst scholar who studied and paid attention to that aspect of communications and came with one of the most original and provocative theory about media and communication systems. Innis’s theoretical legacy is particularly important nowadays as the use of these tools in life is increasing. However, there is not even one single article devoted to present his opinion in Turkish and this is an important missing part for the literature. Innis examined the communication tools on the basis of their relation with time and space. He examined them under two main categories: time-bias communications and space bias communications. He tried to understand what these communications mean today and what they have meant for civilizations throughout history. According to him, the means of communication have many cognitive and social effects and the history of civilization can only be understood when these effects are taken into account. In this article, his theories about technologies, communications and social change will be discussed and evaluated. In this context, the article has two main aims. First, to examine Innis’s works and his Teory in the context of his time. Second, to shortly summarize how communications affect society and human beings by giving some historical and contemporary examples. Te article argues that communications are incrisingly becoming both time and space bieas and thus it becomes difficult to understand their effect. Tat recuires more feld work to see all dimentions of the changes they cause.
Do Happy Children Become Happy Adults?
Authors: Doğan Tayfun , Aydın Fatma Tuba
Published: March 2021

Many psychological theories emphasize the significance of early childhood events. A review of the literature reveals that studies concentrate on the consequences of adverse childhood experiences on the physical and mental health of individuals. A few studies have so far examined the effects of positive childhood experiences on mental health. This research aims to investigate the relationship between positive childhood experiences and happiness. 695 adults (488 female and 207 male) participated in the study. Positive Childhood Experiences Scale served to gather the data regarding the childhood experiences, and The Oxford Happiness Questionnaire is employed to measure the happiness of the participants. According to the results of this study, a positive correlation was found between positive childhood experiences and happiness. Positive childhood experiences explain 23% of happiness and 24% of life satisfaction. In parallel to positive childhood experiences points, the happiness and life satisfaction of the participants also increases. According to the happiness level of participants, those who inform to be very happy have higher levels of positive childhood experiences in comparison to those who feel a moderate level of happiness or declare to be unhappy. The results are discussed in the context of the literature.
The Failed Asabiyya and Cultural Suicide in Michel Houellebecq’s Submission
Authors: Haliloğlu Nagihan
Published: March 2021

This article identifies the correspondences that Ibn Khaldun’s concepts of asabiya, mulk and dynasty have in Michel Houellebecq’s 2015 novel Submission. It analyses the work of a contemporary author through the method sketched out by a Muslim scholar of the 14th century, thereby provincializing a European text, and showing the continuities of cultural thought in the Mediterranean. While putting the role of asabiya at the centre, the article deploys Dipesh Chakrabarty’s understanding of provincialization, and Fernand Braudel’s concept of encounters in the Mediterranean. In Submission, Houellebecq describes a France in which a Muslim candidate has become the president. As the perceived source of Western European culture, Mediterranean has become uncanny, and Houellebecq’s novels reflect this uneasy relationship between the continent and the basin. Houellebecq’s narrator reflects how the decline of France and its apparent cultural suicide is due to lack of solidarity between the classes, how White French people are very quick to adopt the ways of the Maghrebi immigrants, and how, ultimately, the Maghrebi immigrants who are now in power will suffer the same loss of vitality as their White French predecessors. These observations comply with the cyclical social behaviour that Ibn Khaldun has mapped out in the Muqaddimah.
Οργανικές καταλυτικές αντιδράσεις σύνθεσης πολυ-υποκατεστημένων πυρρολίων με τη χρήση ενώσεων του χαλκού
Authors: Ανδρέου Δημήτριος
Published: March 2021

Στην παρούσα διδακτορική διατριβή μελετήθηκαν οι οργανικές καταλυτικές αντιδράσεις σύνθεσης πολυ-υποκατεστημένων πυρρολίων από αλδεΰδες, αμίνες και νιτροαλκένια παρουσία ενώσεων του χαλκού. Αναπτύχθηκε μια νέα μεθοδολογία σύνθεσης τρι-, τετρα- και πεντα-υποκατεστημένων πυρρολίων καθώς και συμπυκνωμένων πυρρολίων σε καλές έως υψηλές αποδόσεις. Τα αποτελέσματα συνοψίζονται ως εξής: Στην ενότητα 2.1 πραγματοποιήθηκε μελέτη σύνθεσης πολυ-υποκατεστημένων πυρρολίων από αλειφατικές αλδεΰδες, αμίνες και νιτροαλκένια παρουσία ενώσεων του χαλκού. Η νέα αυτή μεθοδολογία, με τη χρήση απλών αλδεϋδών, οδηγεί στα τρι- και τετρα-υποκατεστημένα πυρρόλια ενώ με τη χρήση α-μεθυλο-υποκατεστημένων αλδεϋδών η αντίδραση πραγματοποιείται μέσω μιας 1,2-φαινυλο/αλκυλο μετάθεσης που οδηγεί στη σύνθεση των τετρα- και πεντα-υποκατεστημένων πυρρολίων. Επίσης πραγματοποιήθηκε μηχανιστική μελέτη για την εύρεση ενός πιθανού μηχανισμού της αντίδρασης σύνθεσης πολυ-υποκατεστημένων πυρρολίων. Στην ενότητα 2.2 πραγματοποιήθηκε μελέτη σύνθεσης συμπυκνωμένων πυρρολίων από αλδεΰδες με αλειφατικό δακτύλιο, αμίνες και β-νιτροστυρόλια παρουσία καταλύτη χαλκού. Η αντίδραση πραγματοποιείται μέσω επέκτασης του αλειφατικού δακτυλίου της αλδεΰδης κατά ένα άτομο άνθρακα. Επίσης πραγματοποιήθηκαν αντιδράσεις ελέγχου ενδιαμέσων για την εύρεση ενός πιθανού μηχανισμού της αντίδρασης σύνθεσης συμπυκνωμένων πυρρολίων. Στην ενότητα 2.3 πραγματοποιήθηκε μελέτη σύνθεσης πολυ-υποκατεστημένων πυρρολίων από αλδεΰδες αμίνες και νιτροαλκένια παρουσία ενώσεων του χαλκού μέσω μιας one-pot δύο σταδίων διαδοχικής αντίδρασης κυκλοποίησης και αντίδρασης Michael με νιτροαλκένια. Στο πρώτο στάδιο πραγματοποιείται ο σχηματισμός του πυρρολίου και στο δεύτερο στάδιο πραγματοποιείται μια in situ προσθήκη Michael του πυρρολίου στο νιτροαλκένιο προς το σχηματισμό μιας νέα κατηγορίας πολυ-υποκατεστημένων πυρρολίων. Στην ενότητα 2.4 πραγματοποιήθηκαν προσπάθειες γενίκευσης της μεθοδολογίας σύνθεσης πολυ-υποκατεστημένων πυρρολίων με τη μελέτη διαφορετικών αντιδραστηρίων με σκοπό να συντεθούν πολυ-υποκατεστημένα πυρρόλια με διαφορετικούς υποκαταστάτες. Χρησιμοποιήθηκαν νέα ηλεκτρονιόφιλα αντιδραστήρια και πραγματοποιήθηκαν προσπάθειες σύνθεσης NH-πυρρολίων.
A national survey of community rehabilitation service provision for people with long Covid in Scotland
Authors: Duncan Edward , Cooper Kay , Cowie Julie , Alexander Lyndsay , Morris Jacqui , Preston Jenny
Published: March 2021

Background: Over 50 million cases of COVID-19 have been confirmed globally as of November 2020. Evidence is rapidly emerging on the epidemiology of COVID-19, and its impact on individuals and potential burden on health services and society. Between 10–35% of people with COVID-19 may experience post-acute long Covid. This currently equates to between 8,129 and 28,453 people in Scotland. Some of these people will require rehabilitation to support their recovery. Currently, we do not know how to optimally configure community rehabilitation services for people with long Covid.

Methods: This national survey aimed to provide a detailed description of current community rehabilitation provision for people with long Covid in Scotland. We developed, piloted, and conducted a national electronic survey of current community rehabilitation service provision for people presenting with long Covid symptomatology. Our sample were the Allied Health Professions Directors of all 14 territorial NHS Health Boards in Scotland. Fixed response and narrative data were analysed descriptively.

Results: Responses were received from all respondents (14/14), enabling a national picture to be gained. Almost all Health Boards (13/14) currently deliver rehabilitation for people with long Covid within pre-existing services. Fatigue (11/14) and respiratory conditions (9/14) were the two most common presenting problems of patients. Most long Covid community rehabilitation services are delivered through a combination of face-to-face and digital contact (13/14).

Conclusions: Community rehabilitation for people with long Covid is an emerging reality. This survey provides a national picture of current community rehabilitation for people with long Covid. We do not know how community rehabilitation can be optimally delivered for this population. This is vital as community rehabilitation services were already under pressure prior to the emergence of COVID-19. Further research is urgently required to investigate the implementation, outcomes and cost-effectiveness of differing models of community rehabilitation for this patient population.