bluuebunny/crossref_metadata_2025 huggingface dataset:
Thermodynamic basis of the α-helix and DNA duplex
Authors: Dragan A. I. , Crane-Robinson C. , Privalov P. L.
Published: April 2021

Analysis of calorimetric and crystallographic information shows that the α-helix is maintained not only by the hydrogen bonds between its polar peptide groups, as originally supposed, but also by van der Waals interactions between tightly packed apolar groups in the interior of the helix. These apolar contacts are responsible for about 60% of the forces stabilizing the folded conformation of the α-helix and their exposure to water on unfolding results in the observed heat capacity increment, i.e. the temperature dependence of the melting enthalpy. The folding process is also favoured by an entropy increase resulting from the release of water from the peptide groups. A similar situation holds for the DNA double helix: calorimetry shows that the hydrogen bonding between conjugate base pairs provides a purely entropic contribution of about 40% to the Gibbs energy while the enthalpic van der Waals interactions between the tightly packed apolar parts of the base pairs provide the remaining 60%. Despite very different structures, the thermodynamic basis of α-helix and B-form duplex stability are strikingly similar. The general conclusion follows that the stability of protein folds is primarily dependent on internal atomic close contacts rather than the hydrogen bonds they contain.
Human leukocyte antigen I is significantly downregulated in patients with myxoid liposarcomas
Authors: Oike Naoki , Kawashima Hiroyuki , Ogose Akira , Hatano Hiroshi , Ariizumi Takashi , Yamagishi Tetsuro , Murayama Yudai , Umezu Hajime , Imai Chihaya , Hayashi Masanori , Endo Naoto
Published: April 2021

The characteristics of the tumor immune microenvironment remains unclear in liposarcomas, and here we aimed to determine the prognostic impact of the tumor immune microenvironment across separate liposarcomas subtypes. A total of 70 liposarcoma patients with three subtypes: myxoid liposarcoma (n = 45), dedifferentiated liposarcoma (n = 17), and pleomorphic liposarcoma (n = 8) were enrolled. The presence of tumor infiltrating lymphocytes (CD4+ , CD8+ , FOXP3+ lymphocytes) and CD163+ macrophages and expression of HLA class I and PD-L1 were assessed by immunohistochemistry in the diagnostic samples; overall survival and progression-free survival were estimated from outcome data. For infiltrating lymphocytes and macrophages, dedifferentiated liposarcoma and pleomorphic liposarcoma patients had a significantly higher number than myxoid liposarcoma patients. While myxoid liposarcoma patients with a high number of macrophages were associated with worse overall and progression-free survival, dedifferentiated liposarcoma patients with high macrophage numbers showed a trend toward favorable prognosis. Expression of HLA class I was negative in 35 of 45 (77.8%) myxoid liposarcoma tumors, whereas all dedifferentiated liposarcoma and pleomorphic liposarcoma tumors expressed HLA class I. The subset of myxoid liposarcoma patients with high HLA class I expression had significantly poor overall and progression-free survival, while dedifferentiated liposarcoma patients with high HLA class I expression tended to have favorable outcomes. Only four of 17 (23.5%) dedifferentiated liposarcomas, two of eight (25%) pleomorphic liposarcomas, and no myxoid liposarcoma tumors expressed PD-L1. Our results demonstrate the unique immune microenvironment of myxoid liposarcomas compared to other subtypes of liposarcomas, suggesting that the approach for immunotherapy in liposarcomas should be based on subtype.
Update on Incidence, Prevalence, Treatment and Survival of Patients with Small Bowel Neuroendocrine Neoplasms in the Netherlands
Authors: Kaçmaz Enes , Sarasqueta Arantza Farina , van Eeden Susanne , Dreijerink Koen M. A. , Klümpen Heinz‐Josef , Tanis Pieter J. , van Dijkum Els J. M. Nieveen , Engelsman Anton F.
Published: April 2021

Background

Small bowel neuroendocrine neoplasms (SB‐NEN) are rare cancers, population‐based studies are needed to study this rare indolent disease. The aim of this study was to explore trends in epidemiology, treatment and survival outcomes of patients with SB‐NEN based on Dutch nationwide data.

Patients and methods

Patients with grade 1 or 2 SB‐NEN diagnosed between 2005 and 2015 were retrieved from the Netherlands Cancer Registry and linked to The Nationwide Network and Registry of Histo‐ and Cytopathology in the Netherlands. Age‐adjusted incidence rates were calculated based using the direct standardization method. Survival analyses were performed with the Kaplan–Meier method.

Results

A total of 1132 patients were included for epidemiological analyses. The age‐adjusted incidence rate of SB‐NEN increased from 0.52 to 0.81 per 100.000 person‐years between 2005 and 2015. Incidence was higher for males than females (0.93 vs. 0.69 in 2015). Most patients had grade 1 tumours (83%). Surgery was performed in 86% of patients, with resection of the primary tumour in 99%. During the study period, administration of somatostatin analogues (SSAs) increased from 5 to 22% for stage III and from 27 to 63% for stage IV disease. Mean follow‐up was 61 (standard deviation 38) months. Survival data were complete for 975/1132 patients and five‐year overall survival was 75% for stage I‐II, 75% for stage III and 57% for stage IV.

Conclusions

This study shows an increase in the incidence of SB‐NEN in the Netherlands. A predominant role of surgery was found in all disease stages. Use of SSAs has increased over time.
Assessing Differences in Lymph Node Metastasis Based Upon Sex in Early Non‐Small Cell Lung Cancer
Authors: Deng Han‐Yu , Liu Chang , Qiu Xiao‐Ming , Zhu Da‐Xing , Tang Xiao‐Jun , Zhou Qinghua
Published: April 2021

Backgrounds

Whether sex has any impact on the risk of lymph node (LN) metastasis (LNM) in patients with early‐stage non‐small cell lung cancer (NSCLC) remains controversial. Therefore, we aimed to objectively compared the risk of LNM between female and male patients with early‐stage NSCLC so as to figure out whether sex‐different extent of surgery may be justified for treating these patients.

Methods

We retrospectively collected clinical data of patients undergoing lobectomy or segmentectomy with systematic hilar and mediastinal LN dissection for clinical stage IA peripheral NSCLC from June 2014 to April 2019. Both multivariate logistic regression analysis and propensity score‐matched(PSM) analysis were applied to compare the risk of LNM between female and male patients.

Results

We finally included a total of 660 patients for analysis. In the analysis of unmatched cohorts, there was no significant different rate of LNM (12.4% Vs 13.9%, P=0.556), hilar/intrapulmonary LNM (8.4% Vs 10.7%, P=0.318) and mediastinal LNM(7.9% Vs 7.5%, P=0.851) between female and male patients. In the multivariate analysis, sex was not found to be an independent predictor of LN in these patients. Moreover, in the analysis of well‐matched cohorts generated by PSM analysis, there was still no significant different rate of LNM (13.8% Vs 13.4%, P=0.892), hilar/intrapulmonary LNM (9.1% Vs 11.2%, P=0.442) and mediastinal LNM (9.1% Vs 6.5%, P=0.289) between female and male patients.

Conclusions

Sex was not an independent predictor of LNM in early‐stage NSCLC and there is no sufficient evidence justifying for sex‐different extent of surgical resection for these patients.
Diagnosing necrotizing external otitis on CT and MRI: assessment of pattern of extension
Authors: van der Meer Wilhelmina L. , Waterval Jérôme J. , Kunst Henricus P. M. , Mitea Cristina , Pegge Sjoert A. H. , Postma Alida A.
Published: April 2021

Background and purpose

Necrotizing external otitis (NEO) is a serious complication of external otitis. NEO can be classified according to—anterior, medial, posterior, intracranial, and contralateral—extension patterns. Currently there is no consensus on the optimal imaging modality for the identification of disease extension. This study compares NEO extension patterns on MR and CT to evaluate diagnostic comparability.

Methods

Patients who received a CT and MR within a 3-month interval were retrospectively examined. Involvement of subsites and subsequent spreading patterns were assessed on both modalities by a radiologist in training and by a senior head and neck radiologist. The prevalence of extension patterns on CT and MR were calculated and compared.

Results

All 21 included NEO cases showed an anterior extension pattern on CT and MR. Contrary to MR, medial extension was not recognized on CT in two out of six patients, and intracranial extension in five out of eight patients. The posterior extension pattern was not recognized on MR. Overall, single anterior extension pattern (62%) is more prevalent than multiple extension patterns (38%).

Conclusion

All anterior NEO extension pattern were identified on CT as well as MR. However, the medial and intracranial spreading patterns as seen on MR could only be identified on CT in a small number of patients. The posterior spreading pattern can be overlooked on MR. Thus, CT and MR are complimentary for the initial diagnosis and work-up of NEO as to correctly delineate disease extent through the skull base.
Nusinersen treatment in adult patients with spinal muscular atrophy: a safety analysis of laboratory parameters
Authors: Stolte Benjamin , Nonnemacher Michael , Kizina Kathrin , Bolz Saskia , Totzeck Andreas , Thimm Andreas , Wagner Bernd , Deuschl Cornelius , Kleinschnitz Christoph , Hagenacker Tim
Published: April 2021

Background

Nusinersen is an intrathecally administered antisense oligonucleotide (ASO) that improves motor function in patients with spinal muscular atrophy (SMA). In addition to efficacy, the safety of a therapy is the decisive factor for the success of the treatment. For some ASOs, various organ toxicities have been described, such as thrombocytopenia, renal and liver impairment, or coagulation abnormalities. However, systematic data on laboratory parameters under treatment with nusinersen are mainly available from studies in infants and children. Therefore, our aim was to assess the safety of nusinersen therapy in adult SMA patients.

Methods

Laboratory data from 404 nusinersen injections performed in 50 adult patients with SMA type 2 and type 3 were retrospectively analyzed.

Results

The total observation period was 76.9 patient-years, and patients received up to 12 injections. Our data provides no new safety concerns. In cerebrospinal fluid (CSF), the mean white blood cell count and lactate remained stable over time. Total CSF protein increased by 2.9 mg/dL. No change in mean platelet count was observed under therapy. Only one patient showed sporadic mild thrombocytopenia. Coagulation parameters and inflammatory markers were stable. The mean creatinine level decreased by 0.09 mg/dL. Analysis of mean liver enzyme levels revealed no relevant changes during treatment.

Conclusion

Our data demonstrate a favorable safety profile of nusinersen therapy in adult SMA patients under longer-term “real-world” conditions. In particular, we found no evidence of clinically relevant platelet declines, coagulopathies, or renal or hepatic organ toxicities, which are common concerns with the use of ASOs.
Endoscopic resection with adjuvant treatment versus esophagectomy for early-stage esophageal cancer
Authors: Huang Binhao , Xu Maria Christine , Pennathur Arjun , Li Zhigang , Liu Zhiguo , Wu Qi , Wang Jing , Luo Kongjia , Bai Jianying , Wei Zhi , Xiang Jiaqing , Fang Wentao , Zhang Jie
Published: April 2021

Objective

To evaluate the outcome following the strategy of endoscopic R0 resection (ER) plus adjuvant treatment (AT) versus esophagectomy for esophageal squamous cell cancer in T1a invading muscularis mucosa (M3)-T1b stage.

Methods

We evaluated the outcomes of 46 esophageal squamous cell cancer (ESCC) patients with T1aM3-T1b stage who underwent ER + AT from the Esophageal Cancer Endoscopic Therapy Consortium (ECETC) and compared these outcomes to 92 patients who underwent esophagectomy. Propensity score matching (1:2) was used, with overall survival (OS) and relapse-free survival (RFS) being compared between the two groups.

Results

During a median follow-up of 32 months, there were no statistical differences (P = 0.226) in OS between the two groups. The 1-, 2-, and 3-year overall survival in the esophagectomy group was 95%, 91%, and 84%, respectively. There were no mortalities within three years in the ER + AT group. The RFS between the two groups was also not significantly different (P = 0.938). The 1-, 2-, and 3-year RFS of patients in the esophagectomy group was 90%, 90%, and 83%, respectively, while it was 97%, 94%, and 74% in the ER + AT group, respectively. The local recurrence rates between the two groups were not significantly different (P = 0.277).

Conclusions

This first multicenter analysis showed similar outcomes were found regarding OS and RFS between the two groups in T1aM3-T1b stage patients. ER + AT may be considered in high-risk patients or for those who refuse esophagectomy.
Addition of high C:N crop residues to a P-limited substrate constrains the benefits of arbuscular mycorrhizal symbiosis for wheat P and N nutrition
Authors: Ingraffia Rosolino , Saia Sergio , Giovino Antonio , Amato Gaetano , Badagliacca Giuseppe , Giambalvo Dario , Martinelli Federico , Ruisi Paolo , Frenda Alfonso S.
Published: April 2021

Many aspects concerning the role of arbuscular mycorrhizal (AM) fungi in plant nutrient uptake from organic sources remain unclear. Here, we investigated the contribution of AM symbiosis to N and P uptake by durum wheat after the addition of a high C:N biomass to a P-limited soil. Plants were grown in pots in the presence or absence of a multispecies AM inoculum, with (Org) or without (Ctr) the addition of 15N-labelled organic matter (OM). A further treatment, in which 15N was applied in mineral form (Ctr+N) in the same amount as that supplied in the Org treatment, was also included. Inoculation with AM had positive effects on plant growth in both control treatments (Ctr and Ctr+N), mainly linked to an increase in plant P uptake. The addition of OM, increasing the P available in the soil for the plants, resulted in a marked decrease in the contribution of AM symbiosis to plant growth and nutrient uptake, although the percentage of mycorrhization was higher in the Org treatment than in the controls. In addition, mycorrhization drastically reduced the recovery of 15N from the OM added to the soil whereas it slightly increased the N recovery from the mineral fertiliser. This suggests that plants and AM fungi probably exert a differential competition for different sources of N available in the soil. On the whole, our results provide a contribution to a better understanding of the conditions under which AM fungi can play an effective role in mitigating the negative effects of nutritional stresses in plants.
Experimental observations of aquifer storage and recovery in brackish aquifers using multiple partially penetrating wells
Authors: Witt Lilli , Müller Moritz J. , Gröschke Maike , Post Vincent E. A.
Published: April 2021

Aquifer storage and recovery systems using multiple partially penetrating wells (MPPW-ASR) can form a viable solution to the problem of freshwater buoyancy when using brackish aquifers for freshwater storage. This study presents the result of a series of laboratory experiments that aimed at visualizing the shape of freshwater bodies injected into a brackish aquifer and determining the effect on the recovery efficiency (RE) of several MPPW-ASR operational variables. A model aquifer was built in a Plexiglas tank using glass beads and water was injected and abstracted through point and vertical wells, which were operated in various combinations. Numerical models were used to support the interpretation of the time-lapse photographs, and showed that three-dimensional flow effects had to be considered for a correct interpretation of the visible dye patterns. Upward migration of both fresh (during injection) and brackish water (during recovery) along the vertical wells was observed, indicating that the role of well infrastructure as conduits is a critical design criterion for real-world systems. Gravitational instabilities formed when freshwater did not extend all the way to the top of the aquifer, and this negatively impacted the RE by causing greater mixing. The positive freshwater buoyancy led to freshwater bodies that became narrower with depth, and the formation of thin, elongated buffer zones along the aquifer top in multicycle experiments. Up-coning below abstraction wells resulted in lower RE values, reinforcing the potential of scavenger wells to enhance MPPW-ASR system performance.
Development of the surface displacement velocity in a full-scale loamy model slope under multistep excavation
Authors: Sasahara Katsuo , Hiraoka Nobutaka , Kikkawa Naotaka , Itoh Kazuya
Published: April 2021

Multistep excavations were implemented at the toe of a large-scale slope model, and the surface displacements in the slope were measured to examine the validity of the relationship between the velocity and acceleration proposed by Fukuzono for excavated slopes. The surface displacement increased both during and after slope excavation, among which the latter was due to creep deformation under a constant stress. The rate of increase in the surface displacement was initially high and then decreased to zero during creep deformation after the excavation without slope failure. However, the surface displacement exhibited an accelerated increase during creep deformation after the final excavation prior to slope failure; the surface displacement increased with small fluctuations even before slope failure occurred. The surface displacement velocity and acceleration also fluctuated notably due to variations in the surface displacement. The trendlines for the derived relationships between the velocity and acceleration were in good general agreement with the measured data at certain locations in the model slope. These relationships were unique at different locations on the slope, while the inclination of the relationship trendline suddenly decreased just prior to slope failure. The steeper trendlines predicted an earlier failure time if the displacement was large and close to the failure condition, whereas they resulted in worse predictions if the displacement was small and far from causing slope failure according to the prediction method proposed by Fukuzono.
Determination of initial airtightness after anatomical laser segmentectomy in an ex vivo model
Authors: Kirschbaum Andreas , Ivanovic Andrijana , Wiesmann Thomas , Mirow Nikolas , Meyer Christian
Published: April 2021

If a pulmonary pathology can be removed by anatomical segmentectomy, the need for lobectomy is obviated. The procedure is considered oncologically equivalent and saves healthy lung tissue. In every segmentectomy, lung parenchyma must be transected in the intersegmental plane. Using an ex vivo model based on porcine lung, three transection techniques (monopolar cutter + suture, stapler, and Nd:YAG laser) are to be compared with respect to their initial airtightness. At an inspiratory ventilation pressure of 25 mbar, all three preparations were airtight. Upon further increase in ventilation pressure up to 40 mbar, the laser group performed best in terms of airtightness. Since thanks to its use of a laser fibre, this technique is particularly suitable for minimally invasive surgery; it should be further evaluated clinically for this indication in the future.
A pulsed-Laser Rb atomic frequency standard for GNSS applications
Authors: Micalizio S. , Levi F. , Calosso C. E. , Gozzelino M. , Godone A.
Published: April 2021

We present the results of 10 years of research related to the development of a Rubidium vapor cell clock based on the principle of pulsed optical pumping (POP). Since in the pulsed approach, the clock operation phases take place at different times, this technique demonstrated to be very effective in curing several issues affecting traditional Rb clocks working in a continuous regime, like light shift, with a consequent improvement of the frequency stability performances. We describe two laboratory prototypes of POP clock, both developed at INRIM. The first one achieved the best results in terms of frequency stability: an Allan deviation of σy(τ) = 1.7 × 10−13 τ−1/2, being τ the averaging time, has been measured. In the prospect of a space application, we show preliminary results obtained with a second more recent prototype based on a loaded cavity-cell arrangement. This clock has a reduced size and exhibited an Allan deviation of σy(τ) = 6 × 10−13 τ−1/2, still a remarkable result for a vapor cell device. In parallel, an ongoing activity performed in collaboration with Leonardo S.p.A. and aimed at developing an engineered space prototype of the POP clock is finally mentioned. Possible issues related to space implementation are also briefly discussed. On the basis of the achieved results, the POP clock represents a promising technology for future GNSSs.
A model and algorithm for identifying driver pathways based on weighted non-binary mutation matrix
Authors: Wu Jingli , Zhu Kai , Li Gaoshi , Wang Jinyan , Cai Qirong
Published: April 2021

It is generally acknowledged that driver pathway plays a decisive role in the occurrence and progress of tumors, and the identification of driver pathways has become imperative for precision medicine or personalized medicine. Due to the inevitable sequencing error, the noise contained in single omics cancer data usually plays a negative effect on identification. It is a feasible approach to take advantage of multi-omics cancer data rather than a single one now that large amounts of multi-omics cancer data have become available. The identification of driver pathways by integrating multi-omics cancer data has attracted attention of researchers in bioinformatics recently. In this paper, a weighted non-binary mutation matrix is constructed by integrating copy number variations, somatic mutations and gene expressions. Based on the weighted non-binary mutation matrix, a new identification model is proposed through defining new measurements of coverage and exclusivity. Then, a cooperative coevolutionary algorithm CGA-MWS is put forward for solving the presented model. Both real cancer data and simulated one were used to conduct comparisons among methods Dendrix, GA, iMCMC, MOGA, PGA-MWS and CGA-MWS. Compared with the pathways identified by the other five methods, more genes, belonging to the pathway identified by the CGA-MWS method, are enriched in a known signaling pathway in most cases. Simultaneously, the high efficiency of method CGA-MWS makes it practical in realistic applications. All of which have been verified through a number of experiments.
Efficacy of fluvastatin and aspirin for prevention of hormonally insensitive breast cancer
Authors: Bhardwaj Anjana , Embury Matthew D. , Rojo Raniv D. , Albarracin Constance , Bedrosian Isabelle
Published: April 2021

Purpose

Primary prevention of hormonally insensitive breast cancers remains an important clinical need and repurposing existing low-toxicity drugs represents a low-cost, efficient strategy for meeting this goal. This study targeted the cholesterol pathway using fluvastatin, a cholesterol-lowering drug, and aspirin, an AMPK activator that acts as a brake in the cholesterol pathway, in a transgenic mouse model of triple-negative breast cancer (TNBC).

Methods

Using SV40C3 TAg mice, the efficacy and mechanism of fluvastatin, aspirin, or both in combination were compared with vehicle alone.

Results

Sixteen-weeks of fluvastatin treatment resulted in significant delay in onset of tumors (20 weeks vs. 16.8 weeks in vehicle treatment, p = 0.01) and inhibited tumor incidence and tumor multiplicity by 50% relative to the vehicle control. In animals that developed tumors, fluvastatin treatment inhibited tumor weight by 75% relative to vehicle control. Aspirin alone did not significantly affect tumor latency, tumor incidence or tumor burden compared to vehicle control. Fluvastatin and aspirin in combination delayed the onset of tumors but failed to inhibit tumor incidence and tumor multiplicity. The growth-inhibitory effects of fluvastatin were mediated through increased FAS/FASL mediated apoptotic cell death that was characterized by increased cleaved PARP and driven in part by depletion of an isoprenoid, geranyl geranyl pyrophosphate (GGPP).

Conclusions

In line with NCI’s emphasis to repurpose low-toxicity drugs for prevention of cancer, fluvastatin was effective for prevention of TNBC and warrants further clinical testing. Aspirin did not provide chemopreventive benefit.
Effect of synthetic bone replacement material of different size on shear stress resistance within impacted native and thermodisinfected cancellous bone: an in vitro femoral impaction bone grafting model
Authors: Fölsch C. , Sahm P. , Ulloa C. A. Fonseca , Krombach G. A. , Kampschulte M. , Rickert M. , Pruss A. , Jahnke A.
Published: April 2021

Antibiotic carrier particles of variable size might influence mechanic properties within impacted thermodisinfected and native cancellous bone different. Herafill®G containing calciumsulfate and calciumcarbonate provides high local concentrations of gentamicin being important for revision surgery in infected joint replacements. Native and thermodisinfected cancellous bone derived from 6 to 7 months old piglets was used for in vitro impaction bone grafting and supplemented each with Herafill®G granules of two different sizes. Micromovement of implants related to shear force was measured in 29 specimens distributed in 6 groups. Thermodisinfected cancellous bone revealed a significant higher shear force resistance than native bone with a mean difference of 423.8 mdeg/Nm (p < 0.001) ranging within 95% confidence interval from 181.5 to 666.0 mdeg/Nm. Adding small granules to thermodisinfected bone did not reduce shear force resistance significantly since adding large granules to native bone improved it by 344.0 mdeg/Nm (p < 0.003). Shear force resistance was found higher at the distal region of the implant compared to a proximal point of measurement throughout all specimens. Less impaction impulses were necessary for thermodisinfected bone. Thermodisinfected cancellous bone might achieve a higher degree of impaction compared with native bone resulting in increased resistance against shear force since impaction was found increased distally. Supplementation of thermodisinfected bone with small granules of Herafill®G might be considered for application of local antibiotics. Large granules appeared more beneficial for supplementation of native bone. Heterogeneity of bone graft and technical aspects of the impaction procedure have to be considered regarding the reproducibility of femoral impaction bone grafting.
Decrypting distributed ledger design—taxonomy, classification and blockchain community evaluation
Authors: Ballandies Mark C. , Dapp Marcus M. , Pournaras Evangelos
Published: April 2021

More than 1000 distributed ledger technology (DLT) systems raising $600 billion in investment in 2016 feature the unprecedented and disruptive potential of blockchain technology. A systematic and data-driven analysis, comparison and rigorous evaluation of the different design choices of distributed ledgers and their implications is a challenge. The rapidly evolving nature of the blockchain landscape hinders reaching a common understanding of the techno-socio-economic design space of distributed ledgers and the cryptoeconomies they support. To fill this gap, this paper makes the following contributions: (i) A conceptual architecture of DLT systems with which (ii) a taxonomy is designed and (iii) a rigorous classification of DLT systems is made using real-world data and wisdom of the crowd. (iv) A DLT design guideline is the end result of applying machine learning methodologies on the classification data. Compared to related work and as defined in earlier taxonomy theory, the proposed taxonomy is highly comprehensive, robust, explanatory and extensible. The findings of this paper can provide new insights and better understanding of the key design choices evolving the modeling complexity of DLT systems, while identifying opportunities for new research contributions and business innovation.
Donor demographics and factors affecting corneal utilisation in Eye Bank of North India
Authors: Arya S. K. , Raj Amit , Deswal Jyoti , Kohli Piyush , Rai Raghavendra
Published: April 2021

Introduction

Nearly 6.8 million people in India have vision less than 6/60 in at least one eye due to corneal diseases; of these, about a million had bilateral involvement.

Purpose

To identify the challenges faced; the trends in collection, storage and utilisation of corneal tissues in an eye bank in north India.

Materials and methods

The past records of Eye Bank linked to a tertiary hospital in northern India were analysed from November’1999 to October’2015 with respect to number of eye donations per year, donor demographics and utilisation of corneal tissues.

Results

The number of donations during the first 6 years were 100, 279 in the next 5 years and 473 in the last 5 years. The mean donor age was 63.2 ± 19.5 years. The percentage of donors less than 30, 31–60 and more than 60 years was 10%, 28% and 62%. Forty-two percent donations were from the hospital. The average time between the death and enucleation was 4.74 ± 5.31 hours. The percentage of corneas used in the donor age groups less than 30, 31–60 and above 60 years was 61.9%, 61.6% and 53.8%, respectively. The usability rate of the corneas from home and hospital was 63.7% and 55.3%, respectively.

Conclusions

The eye bank had a lukewarm response in the beginning, but gained momentum with time. The myths and beliefs prevalent in our society deter people from donating eyes freely. Each eye bank needs to individualise its problems and find solutions for adequate procurement and utilisation of tissue.
Baicalin and Geniposide Inhibit Polarization and Inflammatory Injury of OGD/R-Treated Microglia by Suppressing the 5-LOX/LTB4 Pathway
Authors: Li HuiMin , Wang Yan , Wang Bin , Li Min , Liu JiPing , Yang HongLian , Shi YongHeng
Published: April 2021

Cerebral ischemia causes severe neurological disorders and neuronal dysfunction. Baicalin (BC), geniposide (GP), and their combination (BC/GP) have been shown to inhibit post-ischemic inflammatory injury by inhibiting the 5-LOX/CysLTs pathway. The aims of this study were to observe the inhibitory effects of BC/GP on the activation of microglial cells induced by oxygen glucose deprivation and reoxygenation (OGD/R) and to investigate whether the 5-LOX/LTB4 pathway was involved in these effects. Molecular docking showed that BC and GP exhibited considerable binding activity with LTB4 synthase LTA4H. BV-2 microglia were transfected with a 5-LOX overexpression lentiviral vector, and then OGD/R was performed. The effects of different concentrations of BC, GP, and BC/GP (6.25 μM, 12.5 μM, and 25 μM) on cell viability and apoptosis of microglia were evaluated by MTT and flow cytometry. The expression of TNF-α, IL-1β, NF-κB, and pNF-κB also was measured by ELISA, Western blots and immunofluorescence. Western blots and qRT-PCR analysis were used to determine the levels of CD11b, CD206, and 5-LOX pathway proteins. Results showed that BC, GP, and BC/GP reduced the apoptosis caused by OGD/R in a dose-dependent manner, and cell viability was significantly increased at a concentration of 12.5 μM. OGD/R significantly increased the release of TNF-α, IL-1β, NF-κB, pNF-κB, and CD11b. These effects were suppressed by BC, GP, and BC/GP, and the OGD/R-induced transfer of NF-κB p65 from the ctytoplasm to the nucleus was inhibited in microglia. Interestingly, the LTB4 inhibitor, U75302, exhibited the same effect. Also, BC, GP, and BC/GP significantly reduced the expression of 5-LOX pathway proteins. These results demonstrated that BC/GP inhibited OGD/R-induced polarization in BV2 microglia by regulating the 5-LOX/LTB4 signaling pathways and attenuating the inflammatory response. Our results supported the theoretical basis for additional in-depth study of the function of BC/GP and the value of determining its unique target, which might provide a new therapeutic strategy for ischemic cerebrovascular disease.
Optimizing the decoy-state BB84 QKD protocol parameters
Authors: Attema Thomas , Bosman Joost W. , Neumann Niels M. P.
Published: April 2021

Quantum key distribution (QKD) protocols allow for information theoretically secure distribution of (classical) cryptographic key material. However, due to practical limitations the performance of QKD implementations is somewhat restricted. For this reason, it is crucial to find optimal protocol parameters, while guaranteeing information theoretic security. The performance of a QKD implementation is determined by the tightness of the underlying security analysis. In particular, the security analyses determines thekey-rate, i.e., the amount of cryptographic key material that can be distributed per time unit. Nowadays, the security analyses of various QKD protocols are well understood. It is known that optimal protocol parameters, such as the number of decoy states and their intensities, can be found by solving a nonlinear optimization problem. The complexity of this optimization problem is typically handled by making a number of heuristic assumptions. For instance, the number of decoy states is restricted to only one or two, with one of the decoy intensities set to a fixed value, and vacuum states are ignored as they are assumed to contribute only marginally to the secure key-rate. These assumptions simplify the optimization problem and reduce the size of search space significantly. However, they also cause the security analysis to be non-tight, and thereby result in sub-optimal performance. In this work, we follow a more rigorous approach using both linear and nonlinear programs describing the optimization problem. Our approach, focusing on the decoy-state BB84 protocol, allows heuristic assumptions to be omitted, and therefore results in a tighter security analysis with better protocol parameters. We show an improved performance for the decoy-state BB84 QKD protocol, demonstrating that the heuristic assumptions typically made are too restrictive. Moreover, our improved optimization frameworks shows that the complexity of the performance optimization problem can also be handled without making heuristic assumptions, even with limited computational resources available.
Mysticism without concepts
Authors: Gäb Sebastian
Published: April 2021

It has often been claimed, e.g. by William James or Aldous Huxley, that mystical experiences across times and cultures exhibit a striking similarity. Even though the words and images we use to describe them are different, underneath the surface we find a common experiential core. Others have rejected this claim and argued that all experiences are intrinsically shaped by the mystics’ pre-existing religious concepts. Against these constructivist objections, I defend the idea of a common core by arguing that even if all experience is interpreted through concepts,there could still be a common core. Those who reject the common core thesis usually argue that no distinction between experience and interpretation can be made since all experience is per se already interpreted. The notion of an uninterpreted experience is self-defeating. Drawing on current research on nonconceptual mental content, I argue (a) that experiences can have nonconceptual content; (b) that interpretation must be understood as conceptualization and (c) that conceptualization presupposes a raw mental content that is not conceptualized. This raw content is not experienced as nonconceptual. Rather, the nonconceptual, uninterpreted common core is an abstraction which shows itself only through reflection. Thus, the existence of a common core is compatible with the fact that all experiences are interpreted.
Use of an electronic medical record dashboard to identify gaps in osteoporosis care
Authors: Papaioannou A. , McCloskey E. , Bell A. , Ngui D. , Mehan U. , Tan M. , Goldin L. , Langer A.
Published: April 2021

Using an electronic medical record (EMR)-based dashboard, this study explored osteoporosis care gaps in primary care. Eighty-four physicians shared their practice activities related to bone mineral density testing, 10-year fracture risk calculation and treatment for those at high risk. Significant gaps in fracture risk calculation and osteoporosis management were identified.

Purpose

To identify care gaps in osteoporosis management focusing on Canadian clinical practice guidelines (CPG) related to bone mineral density (BMD) testing, 10-year fracture risk calculation and treatment for those at high risk.

Methods

The ADVANTAGE OP EMR tool consists of an interactive algorithm to facilitate assessment and management of fracture risk using CPG. The FRAX® and Canadian Association of Radiologists and Osteoporosis Canada (CAROC) tools were embedded to facilitate 10-year fracture risk calculation. Physicians managed patients as clinically indicated but with EMR reminders of guideline recommendations; participants shared practice level data on management activities after 18-month use of the tool.

Results

Eighty-four physicians (54%) of 154 who agreed to participate in this study shared their aggregate practice activities. Across all practices, there were 171,310 adult patients, 40 years of age and older, of whom 17,214 (10%) were at elevated risk for fracture. Sixty-two percent of patients potentially at elevated risk for fractures did not have BMD testing completed; most common reasons for this were intention to order BMD later (48%), physician belief that BMD was not required (15%) and patient refusal (20%). For patients with BMD completed, fracture risk was calculated in 29%; 19% were at high risk, of whom 37% were not treated with osteoporosis medications as recommended by CPG.

Conclusion

Despite access to CPG and fracture risk calculators through the ADVANTAGE OP EMR tool, significant gaps remain in fracture risk calculation and osteoporosis management. Additional strategies are needed to address this clinical inertia among family physicians.
A survey of general practitioners’ knowledge and clinical practice in relation to valvular heart disease
Authors: Birrane John P. , Lim Zi Lun , Liew Chee H. , Rosseel Liesbeth , Heerey Adrienne , Coleman Kieran , Gallagher Joseph , Mylotte Darren , McEvoy John W.
Published: April 2021

Introduction

General practice has a key role in diagnosing patients with valvular heart disease (VHD) and referring them to appropriate services.

Methods

An anonymous survey was conducted to assess the knowledge and clinical practice behaviour of Irish general practitioners (GPs) in relation to VHD. In addition to demographic data, the survey captured information in the following domains: knowledge of VHD prevalence, knowledge of contemporary VHD treatments, barriers to diagnosis, and referral patterns. To augment responses, a monetary prize (donated to charity) was offered and the survey was also disseminated using social media and by the Irish College of General Practitioners.

Results

Valid survey responses were received from 197 GPs. The sample was well-balanced by gender, number of years in practice, and practice setting. A small proportion of GPs (16.8%) used a stethoscope to examine for VHD in all patients over 60 years, a figure that rose to 22.3% in patients over 75. Approximately half of participants (48%) felt confident in their ability to detect and diagnose VHD using a stethoscope, and 74% felt lack of access to echocardiography was a major barrier to making a VHD diagnosis. There was a high level of awareness among GPs of minimally invasive nonsurgical interventions now available for VHD treatment.

Discussion

Irish GPs displayed good understanding of contemporary VHD treatment options but reported low confidence and inconsistent practices in evaluating patients for VHD. Improved access to echocardiography might help address these deficiencies, but reorganisation of services will be required in a resource-limited public health service.

Graphical abstract
Metabolomics in Advanced Liver Disease
Authors: Kano Noora , Want Elizabeth J. , McPhail Mark J. W.
Published: April 2021

Purpose of review

Cirrhosis is one of the most important global public health problems. Patients with cirrhosis risk progression to acute-on-chronic liver failure (ACLF), associated with high mortality rates, and development of hepatocellular carcinoma (HCC). Metabolomics could identify urgently required novel biomarkers to improve disease diagnosis, monitor progression, and identify therapies.

Recent findings

In this review, current metabolic studies in decompensated cirrhosis, ACLF, and HCC over the past 3 years are summarised. Over numerous metabolomics studies, in cirrhosis, common alterations in proteins, carbohydrates, lipids, bile acids, and microbial metabolites were identified. In ACLF, changes in metabolites related to energy metabolism, amino acids, lipids, bile acids, and microbial metabolites were reported. Amino acids, bile acids, free fatty acids, and phospholipids were identified as important metabolite classes for discrimination between cirrhosis and HCC.

Metabolomics can improve our understanding of advanced liver diseases and provide the basis of the future studies and therapeutic advancements.
Disclosing or Hiding Bullying Victimization: A Grounded Theory Study From Former Victims’ Point of View
Authors: Wójcik Małgorzata , Rzeńca Krzysztof
Published: April 2021

This study aimed to investigate the process of disclosing bullying victimization from the former victims’ point of view. Twenty-three individuals with prior experience of victimization at school were interviewed. A grounded theory approach was used to analyze the data, which generated a grounded theory of help-seeking in victimization, comprising factors and conditions that influenced the willingness to ask for help when bullied. We concentrated on disclosure barriers and facilitators in a school context to identify important factors, which comprised type of peer harassment, type and form of initial attack, perception of available support at school, and perception of peer support. In terms of the practical implications of the present study, the identification of disclosure tendencies could provide a basis for developing school policies to facilitate disclosure.
Urteilsbildung und Entscheidungsfindung von ASD-Fachkräften in der COVID-19-Krise
Authors: Freres Katharina , Benoit Megan , Posmek Jana , Benkel Christopher , Grüßert Nina , Bastian Pascal
Published: April 2021

Über die Auswirkungen der COVID-19-Pandemie auf die Fallarbeit der Jugendämter liegt bislang noch wenig empirisches Wissen vor. Gleichzeitig sind die konkrete Arbeit der Fachkräfte mit Kindern, Jugendlichen und Familien sowie die Entscheidungspraktiken, etwa bezogen auf den Kinderschutz, auch für die gewöhnliche nicht pandemiebedingte Praxis wenig erforscht. Die in dieser Forschungsnotiz vorgestellte Studie basiert auf einem ethnografischen Forschungsprogramm und untersucht die Fallarbeit in der Pandemie. Aus einer relationalen Perspektive, die den Blick nicht alleine auf die jeweiligen Akteur*innen sondern vielmehr auf deren Verbindungen und Vernetzungen untereinander richtet, sollen Verschiebungen des Netzwerks, in dem die Fälle üblicherweise bearbeitet werden, sichtbar gemacht und Praktiken, die sich als Bewältigungsstrategien der veränderten Praxis fassen lassen, offengelegt werden.
Recent Progress in Fiber Optofluidic Lasing and Sensing
Authors: Yang Xi , Gong Chaoyang , Liu Yiling , Rao Yunjiang , Smietana Mateusz , Gong Yuan
Published: April 2021

Fiber optofluidic laser (FOFL) integrates optical fiber microcavity and microfluidic channel and provides many unique advantages for sensing applications. FOFLs not only inherit the advantages of lasers such as high sensitivity, high signal-to-noise ratio, and narrow linewidth, but also hold the unique features of optical fiber, including ease of integration, high repeatability, and low cost. With the development of new fiber structures and fabrication technologies, FOFLs become an important branch of optical fiber sensors, especially for application in biochemical detection. In this paper, the recent progress on FOFL is reviewed. We focuse mainly on the optical fiber resonators, gain medium, and the emerging sensing applications. The prospects for FOFL are also discussed. We believe that the FOFL sensor provides a promising technology for biomedical analysis and environmental monitoring.
Development of Nonlinear Finite Element Models of Mortar-Free Interlocked Single Block Column Subjected to Lateral Loading
Authors: Qamar Furqan , Qin Shunde
Published: April 2021

Around the globe, the need for additional housing, due to the increase in world population, has led to the exploration of more cost effective and environmentally friendly forms of construction. Out of many technologies found, mortar-free interlocked masonry systems were developed to eliminate the deficiency of traditional masonry. For such systems against earthquakes, lateral resistance can be enhanced with plaster. But there is a need to further improve the performance of plaster in mortar-free interlocking walls for better ductility. The objective of this study is to develop nonlinear finite element (NLFE) models to explore the likely failure mechanism (e.g. bond failure) of such systems and to do parametric studies more cheaply than constructing many walls. Lateral failure load, load–displacement curves and crack patterns were compared with the experimental results. Parametric studies involving variation in block and plaster compressive strength and plaster thickness were undertaken using TNO DIANA NLFE models. A 150% increase in thickness of plaster only resulted in 28% increase in failure load, and column thickness can be reduced to theoretical 25 mm of blocks with 8 mm of plaster and yet exceed the lateral strength of a 150-mm-thick unplastered column. A cost analysis was also carried out, based on NLFE models, and showed that fibrous plastered column with 25-mm-thickness blocks gave equivalent performance to the 150-mm-thick unplastered column with 67% cost saving.
Isoprenylated Flavonoids as Cav3.1 Low Voltage-Gated Ca2+ Channel Inhibitors from Salvia digitaloides
Authors: Zhao Jian-Jun , Li Song-Yu , Xia Fan , Hu Ya-Li , Nian Yin , Xu Gang
Published: April 2021

Saldigones A–C (1, 3, 4), three new isoprenylated flavonoids with diverse flavanone, pterocarpan, and isoflavanone architectures, were characterized from the roots of Salvia digitaloides, together with a known isoprenylated flavanone (2). Notably, it’s the first report of isoprenylated flavonoids from Salvia species. The structures of these isolates were elucidated by extensive spectroscopic analysis. All of the compounds were evaluated for their activities on Cav3.1 low voltage-gated Ca2+ channel (LVGCC), of which 2 strongly and dose-dependently inhibited Cav3.1 peak current.

Graphic Abstract