bluuebunny/crossref_metadata_2025 huggingface dataset:
Development, characterization, and hematopoietic differentiation of Griscelli syndrome type 2 induced pluripotent stem cells
Authors: Güney-Esken Gülen , Erol Özgür Doğuş , Pervin Burcu , Gürhan Sevinç Gülben , Önder Tamer , Bilgiç Elif , Korkusuz Petek , Günel-Özcan Ayşen , Uçkan-Çetinkaya Duygu , Aerts-Kaya Fatima
Published: May 2021

Background

Griscelli syndrome type 2 (GS-2) is a rare, autosomal recessive immune deficiency syndrome caused by a mutation in the RAB27A gene, which results in the absence of a protein involved in vesicle trafficking and consequent loss of function of in particular cytotoxic T and NK cells. Induced pluripotent stem cells (iPSC) express genes associated with pluripotency, have the capacity for infinite expansion, and can differentiate into cells from all three germ layers. They can be induced using integrative or non-integrative systems for transfer of the Oct4, Sox2, Klf4, and cMyc (OSKM) transcription factors. To better understand the pathophysiology of GS-2 and to test novel treatment options, there is a need for an in vitro model of GS-2.

Methods

Here, we generated iPSCs from 3 different GS-2 patients using lentiviral vectors. The iPSCs were characterized using flow cytometry and RT-PCR and tested for the expression of pluripotency markers. In vivo differentiation to cells from all three germlines was tested using a teratoma assay. In vitro differentiation of GS-2 iPSCs into hematopoietic stem and progenitor cells was done using Op9 feeder layers and specified media.

Results

All GS-2 iPSC clones displayed a normal karyotype (46XX or 46XY) and were shown to express the same RAB27A gene mutation that was present in the original somatic donor cells. GS-2 iPSCs expressed SSEA1, SSEA4, TRA-1-60, TRA-1-81, and OCT4 proteins, and SOX2, NANOG, and OCT4 expression were confirmed by RT-PCR. Differentiation capacity into cells from all three germ layers was confirmed using the teratoma assay. GS-2 iPSCs showed the capacity to differentiate into cells of the hematopoietic lineage.

Conclusions

Using the lentiviral transfer of OSKM, we were able to generate different iPSC clones from 3 GS-2 patients. These cells can be used in future studies for the development of novel treatment options and to study the pathophysiology of GS-2 disease.
Adrenomedullin 2 improves bone regeneration in type 1 diabetic rats by restoring imbalanced macrophage polarization and impaired osteogenesis
Authors: Wang Feng , Kong Lingchi , Wang Wenbo , Shi Li , Wang Mengwei , Chai Yimin , Xu Jia , Kang Qinglin
Published: May 2021

Background

Both advanced glycation end products (AGEs) and AGE-mediated M1 macrophage polarization contribute to bone marrow mesenchymal stem cell (BMSC) dysfunction, leading to impaired bone regeneration in type 1 diabetes mellitus (T1DM). Adrenomedullin 2 (ADM2), an endogenous bioactive peptide belonging to the calcitonin gene-related peptide family, exhibits various biological activities associated with the inhibition of inflammation and reduction of insulin resistance. However, the effects and underlying mechanisms of ADM2 in AGE-induced macrophage M1 polarization, BMSC dysfunction, and impaired bone regeneration remain poorly understood.

Methods

The polarization of bone marrow-derived macrophages was verified using flow cytometry analysis. Alkaline phosphatase (ALP) staining, ALP activity detection, and alizarin red staining were performed to assess the osteogenesis of BMSCs. Quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, western blotting, and immunofluorescence staining were used to assess polarization markers, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling, and osteogenic markers. In vivo, a distraction osteogenesis (DO) rat model with T1DM was established, and tibia samples were collected at different time points for radiological, biomechanical, and histological analyses, to verify the effects of ADM2 on bone regeneration and M2 polarization under diabetic conditions.

Results

ADM2 treatment reversed AGE-induced M1 macrophage polarization towards the M2 phenotype, which was partially achieved by the peroxisome proliferator-activated receptor γ (PPARγ)-mediated inhibition of NF-κB signaling. The PPARγ inhibitor GW9662 significantly attenuated the effects of ADM2. Besides, ADM2 treatment improved the AGE-impaired osteogenic potential of BMSCs in vitro. Furthermore, ADM2 accelerated bone regeneration, as revealed by improved radiological and histological manifestations and biomechanical parameters, accompanied by improved M2 macrophage polarization in diabetic DO rats, and these effects were partially blocked by GW9662 administration.

Conclusions

These results indicate that ADM2 enhances diabetic bone regeneration during DO, by attenuating AGE-induced imbalances in macrophage polarization, partly through PPARγ/NF-κB signaling, and improving AGE-impaired osteogenic differentiation of BMSCs simultaneously. These findings reveal that ADM2 may serve as a potential bioactive factor for promoting bone regeneration under diabetic conditions, and imply that management of inflammation and osteogenesis, in parallel, may present a promising therapeutic strategy for diabetic patients during DO treatment.
Comparison of structure- and ligand-based scoring functions for deep generative models: a GPCR case study
Authors: Thomas Morgan , Smith Robert T. , O’Boyle Noel M. , de Graaf Chris , Bender Andreas
Published: May 2021

Deep generative models have shown the ability to devise both valid and novel chemistry, which could significantly accelerate the identification of bioactive compounds. Many current models, however, use molecular descriptors or ligand-based predictive methods to guide molecule generation towards a desirable property space. This restricts their application to relatively data-rich targets, neglecting those where little data is available to sufficiently train a predictor. Moreover, ligand-based approaches often bias molecule generation towards previously established chemical space, thereby limiting their ability to identify truly novel chemotypes. In this work, we assess the ability of using molecular docking via Glide—a structure-based approach—as a scoring function to guide the deep generative model REINVENT and compare model performance and behaviour to a ligand-based scoring function. Additionally, we modify the previously published MOSES benchmarking dataset to remove any induced bias towards non-protonatable groups. We also propose a new metric to measure dataset diversity, which is less confounded by the distribution of heavy atom count than the commonly usedinternal diversitymetric. With respect to the main findings, we found that when optimizing the docking score against DRD2, the model improves predicted ligand affinity beyond that of known DRD2 active molecules. In addition, generated molecules occupy complementary chemical and physicochemical space compared to the ligand-based approach, and novel physicochemical space compared to known DRD2 active molecules. Furthermore, the structure-based approach learns to generate molecules that satisfy crucial residue interactions, which is information only available when taking protein structure into account. Overall, this work demonstrates the advantage of using molecular docking to guide de novo molecule generation over ligand-based predictors with respect to predicted affinity, novelty, and the ability to identify key interactions between ligand and protein target. Practically, this approach has applications in early hit generation campaigns to enrich a virtual library towards a particular target, and also in novelty-focused projects, where de novo molecule generation either has no prior ligand knowledge available or should not be biased by it.
Virtual reality vs. Kalinox® for management of pain in intensive care unit after cardiac surgery: a randomized study
Authors: Laghlam Driss , Naudin Cecile , Coroyer Lucas , Aidan Vincent , Malvy Julien , Rahoual Ghilas , Estagnasié Philippe , Squara Pierre
Published: May 2021

Introduction

The management of pain and anxiety remains a challenge in the intensive care unit. By distracting patients, virtual reality (VR) may have a role in painful procedures. We compared VR vs. an inhaled equimolar mixture of N2O and O2(Kalinox®) for pain and anxiety management during the removal of chest drains after cardiac surgery.

Methods

Prospective, non-inferiority, open-label study. Patients were randomized, for Kalinox® or VR session during drain removal. The analgesia/nociception index (ANI) was monitored during the procedure for objective assessment of pain and anxiety. The primary endpoint was the ΔANI (ANImin − ANI0) during the procedure, based on ANIm (average on 4 min). We prespecified VR as non-inferior to Kalinox® with a margin of 3 points. Self-reported pain and anxiety were also analysed using numeric rate scale (NRS).

Results

200 patients were included, 99 in the VR group and 101 in the Kalinox® group; 90 patients were analysed in both groups in per-protocol analysis. The median age was 68.0 years [60.0–74.8]. The ΔANI was − 15.1 ± 12.9 in the Kalinox® group and − 15.7 ± 11.6 in the VR group (NS). The mean difference was, therefore, − 0.6 [− 3.6 to 2.4], including the non-inferiority margin of 3. Patients in the VR group had a significantly higher pain NRS scale immediately after the drain removal, 5.0 [3.0–7.0] vs. 3.0 [2.0–6.0],p = 0.009, but no difference 10 min after. NRS of anxiety did not differ between the two groups.

Conclusion

Based on the ANI, the current study showed that VR did not reach the statistical requirements for a proven non-inferiority vs. Kalinox® in managing pain and anxiety during chest drain removal. Moreover, VR was less effective based on NRS. More studies are needed to determine if VR might have a place in the overall approach to pain and anxiety in intensive care units.

Trial registrationNCT, NCT03956264. Registered 20 May 2019,https://clinicaltrials.gov/ct2/show/NCT03956264
The Parseval identity for q-Sturm–Liouville problems with transmission conditions
Authors: Palamut Koşar Nida
Published: May 2021

In the present study, we investigate the existence of spectral functions and obtain the Parseval identity and expansion formula in eigenfunctions for the singular q-Sturm–Liouville problem with transmission conditions.
Prevalence and associated factors of dyslipidaemia among university workers in Southeast Nigeria: a cross-sectional study
Authors: Okafor Adaobi M. , Ngwu Elizabeth K. , Ayogu Rufina N.B.
Published: May 2021

Background

The job one does for a living may increase ones propensity to cardiovascular diseases due to many associated risk factors. University staff may be at high risk of dyslipidaemia, a major cardiovascular disease risk factor. This study assessed prevalence of dyslipidaemia and its associated factors among the staff of University of Nigeria, Nsukka campus, Nigeria.

Methods

A cross-sectional survey of 386 workers selected through a 4-stage sampling technique was conducted. Data were obtained through questionnaire and lipid profile determination. Bivariate analysis using Cochran and Mantel-Haenszel test was used to determine associations between dyslipidaemia and selected variables. Odds ratios and significance atp < 0.05 were reported.

Results

Respondents who were 46 years and above accounted for 51.3 % while 95.3 % had tertiary education. Administrative/technical staff were 76.4 % while academic staff were only 23.6 %; 73.8 % were senior staff and 26.2 % were junior staff. More than half (60.4 %) consumed alcohol above recommendation. Lipid biomarkers of the workers were not sex dependent (p > 0.05). Few (23.4 and 6.5 %) of the respondents had borderline high and high total cholesterol values, respectively. Whereas none (0.0 %) had low high density lipoprotein cholesterol (HDL-c), borderline low values were observed among 1.3 %. High low density lipoprotein cholesterol (LDL-c) affected 1.3 %. Triglyceride was high among 3.9 %; 20.8 % had high atherogenic index of plasma (AIP) and 2.6 % had impaired fasting blood glucose (IFBG). Dyslipidaemia had a prevalence of 54.5 % with female dominance. Hypercholesterolemia with high LDL-c was the commonest combined dyslipidaemia observed (7.8 %). Dyslipidaemia was dependent on hypercholesterolemia (OR = 0.352, 95 % C.I.=0.245–0.505), high LDL-c (OR = 0.462, 95 % C.I.=0.355-0.600) and hypertriglyceridemia (OR = 0.462, 95 % C.I.=0.355-0.600). Alcohol intake above normal was associated with almost 6 times higher risk of dyslipidaemia (OR = 5.625, 95 % C.I.=1.062–29.799).

Conclusions

Dyslipidaemia is a problem among the workers with hypercholesterolemia in combination with high LDL-c and hypertriglyceridemia compounding the problem. Nutrition education and physical activity are advocated to prevent cardiovascular events among the university staff.
Combination of cell signaling molecules can facilitate MYOD1-mediated myogenic transdifferentiation of pig fibroblasts
Authors: Jeong Jinsol , Choi Kwang-Hwan , Kim Seung-Hun , Lee Dong-Kyung , Oh Jong-Nam , Lee Mingyun , Choe Gyung Cheol , Lee Chang-Kyu
Published: May 2021

Background

Myogenic transdifferentiation can be accomplished through ectopic MYOD1 expression, which is facilitated by various signaling pathways associated with myogenesis. In this study, we attempted to transdifferentiate pig embryonic fibroblasts (PEFs) myogenically into skeletal muscle through overexpression of the pig MYOD1 gene and modulation of the FGF, TGF-β, WNT, and cAMP signaling pathways.

Results

The MYOD1 overexpression vector was constructed based on comparative sequence analysis, demonstrating that pig MYOD1 has evolutionarily conserved domains across various species. Although forced MYOD1 expression through these vectors triggered the expression of endogenous muscle markers, transdifferentiated muscle cells from fibroblasts were not observed. Therefore, various signaling molecules, including FGF2, SB431542, CHIR99021, and forskolin, along with MYOD1 overexpression were applied to enhance the myogenic reprogramming. The modified conditions led to the derivation of myotubes and activation of muscle markers in PEFs, as determined by qPCR and immunostaining. Notably, a sarcomere-like structure was observed, indicating that terminally differentiated skeletal muscle could be obtained from transdifferentiated cells.

Conclusions

In summary, we established a protocol for reprogramming MYOD1-overexpressing PEFs into the mature skeletal muscle using signaling molecules. Our myogenic reprogramming can be used as a cell source for muscle disease models in regenerative medicine and the production of cultured meat in cellular agriculture.
Successful salvage therapy for refractory primary cutaneous gamma-delta T-cell lymphoma with a combination of brentuximab vedotin and gemcitabine
Authors: Voruz Sophie , de Leval Laurence , Cairoli Anne
Published: May 2021

Primary cutaneous gamma-delta T-cell lymphoma (PCGD-TCL) is a very rare lymphoma with an aggressive clinical course and a dismal outcome. The prognosis is linked to a pronounced resistance to chemotherapy and radiotherapy. No standard treatment approach is defined due to the low frequency of the disease and lack of prospective studies. CD30 is expressed in almost half of the cases of PCGD-TCL, which offers a potential therapeutic option. We report the successful treatment of a 68-year-old man who suffered PCGD-TCL with a combination of Brentuximab Vedotin and Gemcitabine after the failure of two lines of previous chemotherapy. CD30 expression was only partial. The treatment was very well tolerated and allowed the patient to benefit from allogeneic hematopoietic stem cell transplantation.
Spatial structure in migration routes maintained despite regional convergence among eastern populations of Swainson’s Thrushes
Authors: Bégin-Marchand Camille , Desrochers André , Taylor Philip D. , Tremblay Junior A. , Berrigan Lucas , Frei Barbara , Morales Ana , Mitchell Greg W.
Published: May 2021

Background

Migratory connectivity links the different populations across the full cycle and across the species range and may lead to differences in survival among populations. Studies on spatial and temporal migratory connectivity along migration routes are rare, especially for small migratory animals.

Methods

We used an automated radio-telemetry array to assess migratory connectivity en route and between early and later stages of the fall migration of the eastern populations of Swainson’s Thrush, and to assess the variation of migration pace between consecutive detection from the different receiving stations along the migratory journey. We tracked 241 individuals from across eastern Canada to determine if populations were mixing around the Gulf of Mexico. We also tested the influence of tagging longitude, latitude and age on migration pace.

Results

Migration routes varied and converged towards the northeast coast of the Gulf of Mexico, but in this region, populations maintained finer-scale spatial structure. Migration pace increased as birds progressed south, independent of age and tagging site.

Conclusions

We showed that for songbirds, migratory connectivity can be maintained at fine spatial scales despite the regional convergence of populations, highlighting the importance of detailed spatial tracking for identification of population specific migration routes. Overall, our study provides a portrait of migratory movements of eastern Swainson’s Thrush and a framework for understanding spatial structure in migration routes for other species.
A Guarneri violin in the attic: the power of dendrochronology for analysing musical instruments
Authors: Bernabei Mauro
Published: May 2021

Dendrochronology is the science that dates wooden artefacts by measuring annual growth rings visible in the wood. And, in the case of musical instruments, the method is non-invasive. In addition, dendrochronology can also help to identify the wood’s provenance and to supply information on how the soundboard was made, giving details of ring width and regularity. This study also demonstrates the effectiveness of dendrochronology in attributing a musical instrument to an important luthier. It deals with a privately owned violin, whose date and origin had previously remained uncertain, despite various attempts to authenticate, at least, its technical and stylistic characteristics. The outermost tree-ring of the instrument’s soundboard was dendrochronologically dated to the year 1696 and attributed, with certainty, to the Italian luthier Giuseppe Guarneri filius Andreae, father of the famous Bartolomeo Giuseppe Guarneri "del Gesù". Thanks to dendrochronology, in this way, a twin of an already existing violin has been identified that was made by the same luthier. Both violins are identical in construction, having the same veining and dimensions, and the wood from the same tree was used in all parts, including the soundboard. Dendrochronology has, thus, been proven to be an extremely useful method, which has transformed a violin of uncertain value into a museum piece.
Towards a folksonomy graph-based context-aware recommender system of annotated books
Authors: Qassimi Sara , Abdelwahed El Hassan , Hafidi Meriem , Qazdar Aimad
Published: May 2021

The emergence of collaborative interactions has empowered users by enabling their interactions through tagging practices that create a folksonomy, also called, classification of the shared resources, any identifiable thing or item on the system. In education, tagging is considered a powerful meta-cognitive strategy that successfully engages learners in the learning process. Besides, the collaborative tagging gathers learners’ opinions, thus, provides more comprehensible recommendations. Still, the abundant shared contents are mostly unorganized which makes it hard for users to select and discover the appropriate items of their interests. Thus, the use of recommender systems overcomes the distressing search problem by assisting users in their searching and exploring experience, and suggesting relevant items matching their preferences. In this regard, this article presents a folksonomy graphs based context-aware recommender system (CARS) of annotated books. The generated graphs express the semantic relatedness between these resources, i.e. books, by effectively modeling the folksonomy relationship between user-resource-tag and integrating contextual information within a multi-layer graph referring to a Knowledge Graph (KG). To put our proposal into shape, we model a real-world application of Goodbooks-10k dataset to recommend books. The proposed approach incorporates spectral clustering to deal with the graph partitioning problem. The experimental evaluation shows relevant performance results of graph-based book recommendations.
Statistical study of medium-scale traveling ionospheric disturbances in low-latitude ionosphere using an automatic algorithm
Authors: Cheng Pin-Hsuan , Lin Charles , Otsuka Yuichi , Liu Hanli , Rajesh Panthalingal Krishanunni , Chen Chia-Hung , Lin Jia-Ting , Chang M. T.
Published: May 2021

This study investigates the medium-scale traveling ionospheric disturbances (MSTIDs) statistically at the low-latitude equatorial ionization anomaly (EIA) region in the northern hemisphere. We apply the automatic detection algorithm including the three-dimensional fast Fourier transform (3-D FFT) and support vector machine (SVM) on total electron content (TEC) observations, derived from a network of ground-based global navigation satellite system (GNSS) receivers in Taiwan (14.5° N geomagnetic latitude; 32.5° inclination), to identify MSTID from other waves or irregularity features. The obtained results are analyzed statistically to examine the behavior of low-latitude MSTIDs. Statistical results indicate the following characteristics. First, the southward (equatorward) MSTIDs are observed almost every day during 0800–2100 LT in Spring and Winter. At midnight, southward MSTIDs are more discernible in Summer and majority of them are propagating from Japan to Taiwan. Second, northward (poleward) MSTIDs are more frequently detected during 1200–2100 LT in Spring and Summer with the secondary peak of occurrence between day of year (DOY) 100–140 during 0000–0300 LT. The characteristics of the MSTIDs are interpreted with additional observations from radio occultation (RO) soundings of FORMOSAT-3/COSMIC as well as modeled atmospheric waves from the high-resolution Whole Atmosphere Community Climate Model (WACCM) suggesting that the nighttime MSTIDs in Summer is likely connected to the atmospheric gravity waves (AGWs).
Transperineal total mesorectal excision for rectal cancer on the residual rectum after multiple abdominal surgeries in a patient with Crohn’s disease: a case report
Authors: Emoto Shin , Homma Shigenori , Yoshida Tadashi , Ichikawa Nobuki , Miyaoka Yoichi , Matsui Hiroki , Takahashi Ryo , Ishido Keita , Otsuka Takuya , Mitsuhashi Tomoko , Katsurada Takehiko , Taketomi Akinobu
Published: May 2021

Background

The improved prognosis of Crohn’s disease may increase the opportunities of surgical treatment for patients with Crohn’s disease and the risk of development of colorectal cancer. We herein describe a patient with Crohn’s disease and a history of multiple surgeries who developed rectal stump carcinoma that was treated laparoscopically and transperineally.

Case presentation

A 51-year-old man had been diagnosed with Crohn’s disease 35 years earlier and had undergone several operations for treatment of Crohn’s colitis. Colonoscopic examination was performed and revealed rectal cancer at the residual rectum. The patient was then referred to our department. The tumor was diagnosed as clinical T2N0M0, Stage I. We treated the tumor by combination of laparoscopic surgery and concomitant transperineal resection of the rectum. While the intra-abdominal adhesion was dissected laparoscopically, rectal dissection in the correct plane progressed by the transperineal approach. The rectal cancer was resected without involvement of the resection margin. The duration of the operation was 3 h 48 min, the blood loss volume was 50 mL, and no intraoperative complications occurred. The pathological diagnosis of the tumor was type 5 well- and moderately differentiated adenocarcinoma, pT2N0, Stage I. No recurrence was evident 3 months after the operation, and no adjuvant chemotherapy was performed.

Conclusion

The transperineal approach might be useful in patients with Crohn’s disease who develop rectal cancer after multiple abdominal surgeries.
Enabling culturally safe sexual health services in western Sydney: a protocol to improve STI treatment outcomes for Aboriginal young people
Authors: Ubrihien Ashley , Gwynne Kylie , Lewis David A.
Published: May 2021

Background

Aboriginal people face challenges on several fronts when it comes to the health and wellbeing of their community, compared to the rest of the Australian population. This is no different in urban areas such as Australia’s largest urban Aboriginal community located in Blacktown, NSW, where sexually transmitted infections (STIs) remain an issue of concern. Across Australia, rates of infectious syphilis, human immunodeficiency virus (HIV), and hepatitis C infection have increased by 400, 260, and 15% respectively while gonorrhoea decreased 12% in the 5-year period from 2013 to 2017. This study explores how to address the barriers that prevent young Aboriginal people under 30 years of age from accessing STI treatment through Government Sexual Health Services.

Methods

This qualitative study will use purposeful sampling to recruit 20 male and 20 female health consumers, 10 Aboriginal elders and 10 sexual health clinicians. This recruitment will be undertaken with the assistance of the local Government Health Services and local Aboriginal organisations. One-on-one semi-structured interviews will be undertaken by someone of the same gender in order to address cultural preferences. Data will be entered into NVivo and thematically analysed.

Discussion

This study will seek to add to the literature that explores why young Aboriginal people do not access sexual health services. This study seeks to understand the experience of clinicians, Aboriginal elders and Aboriginal young people to provide practical policy and clinical redesign evidence that can be used to improve the experience and cultural safety of sexual health services in urban areas of Australia. The results of the qualitative research will be disseminated with the assistance of participating local Aboriginal organisations, and the findings will be published through peer-reviewed scientific journals and conference presentations.

Trial registration

The study is approved by the Western Sydney Local Health District Human Research Ethics Committee (HREC/16/WMEAD/449) and the New South Wales Aboriginal Health and Medical Research Council’s Human Research Ethics Committee (1220/16).
The formation of a hatching line in the serosal cuticle confers multifaceted adaptive functions on the eggshell of a cicada
Authors: Moriyama Minoru , Yasuyama Kouji , Numata Hideharu
Published: May 2021

Insect eggshells must meet various demands of developing embryos. These demands sometimes conflict with each other; therefore, there are tradeoffs between eggshell properties, such as robustness and permeability. To meet these conflicting demands, particular eggshell structures have evolved in diverse insect species. Here, we report a rare eggshell structure found in the eggshell of a cicada,Cryptotympana facialis. This species has a prolonged egg period with embryonic diapause and a trait of humidity-inducible hatching, which would impose severe demands on the eggshell. We found that in eggs of this species, unlike many other insect eggs, a dedicated cleavage site, known as a hatching line, was formed not in the chorion but in the serosal cuticle. The hatching line was composed of a fine furrow accompanied by ridges on both sides. This furrow-ridge structure formed in the terminal phase of embryogenesis through the partial degradation of an initially thick and nearly flat cuticle layer. We showed that the permeability of the eggshell was low in the diapause stage, when the cuticle was thick, and increased with degradation of the serosal cuticle. We also demonstrated that the force required to cleave the eggshell was reduced after the formation of the hatching line. These results suggest that the establishment of the hatching line on the serosal cuticle enables flexible modification of eggshell properties during embryogenesis, and we predict that it is an adaptation to maximize the protective role of the shell during the long egg period while reducing the barrier to emerging nymphs at the time of hatching.
Basel III FRTB: data pooling innovation to lower capital charges
Authors: Huang Jimmy Yicheng
Published: May 2021

Background

Anticipated to overhaul the structure of market risk teams, IT teams, and trading desks within banks by 2023, Basel III's Fundamental Review of the Trading Book requirements will also increase capital charges banks will incur globally. The case study focuses on describing what is needed with regards to the risk factor eligibility test (RFET) as well as for implementing a data pool to lower capital charges. By establishing a consortium of banks per region to implement a data pooling solution, participants can prove a wider breadth of modellable risk factors per asset class and use the Internal Models Approach (IMA) of valuing risk to lower capital charge requirements significantly.

Case description

First, a description on the historical context surrounding the Fundamental Review of the Trading Book rules and the business requirements needed to comply with the risk factor eligibility test is made. Then an examination is conducted on the innovative data pooling initiative implemented by CanDeal, TickSmith Corp., and the 6 largest Canadian banks to lower capital charge requirements under the Fundamental Review of the Trading Book.

Discussion and evaluation

A description is made on what types of data, expertise, and technology is needed to calculate for risk factor modellability. It is up to each firm to decide if the benefits to using the Internal Models Approach to lower capital charges outweighs implementation and running costs of the underlying data platform. Implementing a data pool for each region comes with challenges that include anti-competition law that may block the initiative, varied benefits to each competitive participant, and data security concerns.

Conclusion

It is evident that the data pool innovation provides benefits to lowering capital charges as the Canadian banks have seen an increase of modellability by several factors using the sample bond asset class. While each firm must still determine internally if the benefits outweighs the technological costs they will incur, it is clear that regulators are pushing for increased data retention and scrutiny.
Polarized nature of the COVID-19 pandemic in Japan: associations with population age structure and behaviours
Authors: Okumura Junko
Published: May 2021

Background

Although the scale of the coronavirus disease (COVID-19) pandemic was relatively small in Japan compared with the rest of the world, the polarisation of areas into high- and low-COVID-19-incidence areas was observed among the 47 prefectures. The aims of this study were not only identifying the factors associated with the polarised COVID-19 pandemic in Japan but also discussing effective preventive measures.

Methods

This was an ecological study using online survey data which was cross-sectionally conducted by the author. A total of 6000 respondents who resided in 10 low- and 10 high-COVID-19 incidence prefectures, with a wide gap in terms of COVID-19 incidence, in Japan were recruited. Data on COVID-19 cases and geodemographic information were obtained from official government sites. Statistical analyses were conducted to compare variables between the two areas and age groups.

Results

This study revealed that that age influenced people’s behaviours and perceptions, except one behaviour of ‘wearing facemasks’. The major factors significantly associated with the cumulative number of COVID-19 cases per 100,000 people were ‘commuting by private automobile’ (adjusted odds ratio [AOR], 0.444; 95% confidence interval [CI], 0.394–0.501), ‘commuting by public transportation’ (AOR, 6.813; 95% CI, 5.567–8.336), ‘washing hands’ (AOR, 1.233; 95% CI, 1.005–1.511), ‘opening windows regularly’ (AOR, 1.248; 95% CI, 1.104–1.412), ‘avoiding crowded places (AOR, 0.757; 95% CI, 0.641–0.893), ‘non-scheduled visits to drinking places’ (AOR, 1.212; 95% CI, 1.054–1.392) and ‘perceived risk of contracting COVID-19’ (AOR, 1.380; 95% CI, 1.180–1.612). These factors were strongly associated with age groups.

Conclusions

Effective preventive measures for COVID-19 transmission can be developed by understanding the characteristics of populated areas, such as public transportation infrastructure and younger people’s movements and behaviours in relation to the population age structure to contain the current epidemic and protect the most vulnerable elderly people.
Isolation, identification, and study of the genetic diversity between three entomopathogenic nematodes belonging to Heterorhabditis sp. using ISSR technique
Authors: Khashaba Etr H. K. , Abd El Azim Amany M. A.
Published: May 2021

Background

Entomopathogenic nematodes (EPNs) are widely used in biological control for soil-dwelling stages of many insect pests that are characterized by their safety to most non-target organisms and to the environment.

Results

The objectives of the present study were isolation of EPNs from agricultural soil in Egypt for further use in biological control programs and study the genetic variation among them using the molecular marker inter-simple sequence repeats (ISSR). Three out of 25 soil samples collected from fields cultivated with strawberry, tangerine, and pumpkin were positive for the presence of EPNs, using the Galleria baiting technique. Sequencing of the internal transcribed spacer (ITS) region indicated that the isolates obtained belong to Heterorhabditis sp. The ITS sequences were submitted to the National Center for Biotechnology Information (NCBI) and registered under accession nos. MH553165, MH553168, and MH553169. Six ISSR primers were used. The numbers of polymorphic bands were 42 out of 56, and the polymorphism percentage was 75%. The highest number of bands was 12 bands generated by primer ISSR8 followed by UBC-809 (11 bands) while recorded the lowest band number (4 bands), the percentage of polymorphism ranged from 40% (ISSR1) to 100% (ISSR6).

Conclusion

ISSR marker can be considered a good marker to study genetic diversity and detecting the genetic polymorphism among the nematodes species.
DeepMal: maliciousness-Preserving adversarial instruction learning against static malware detection
Authors: Yang Chun , Xu Jinghui , Liang Shuangshuang , Wu Yanna , Wen Yu , Zhang Boyang , Meng Dan
Published: May 2021

Outside the explosive successful applications of deep learning (DL) in natural language processing, computer vision, and information retrieval, there have been numerous Deep Neural Networks (DNNs) based alternatives for common security-related scenarios with malware detection among more popular. Recently, adversarial learning has gained much focus. However, unlike computer vision applications, malware adversarial attack is expected to guarantee malwares’ original maliciousness semantics. This paper proposes a novel adversarial instruction learning technique, DeepMal, based on an adversarial instruction learning approach for static malware detection. So far as we know, DeepMal is the first practical and systematical adversarial learning method, which could directly produce adversarial samples and effectively bypass static malware detectors powered by DL and machine learning (ML) models while preserving attack functionality in the real world. Moreover, our method conducts small-scale attacks, which could evade typical malware variants analysis (e.g., duplication check). We evaluate DeepMal on two real-world datasets, six typical DL models, and three typical ML models. Experimental results demonstrate that, on both datasets, DeepMal can attack typical malware detectors with the mean F1-score and F1-score decreasing maximal 93.94% and 82.86% respectively. Besides, three typical types of malware samples (Trojan horses, Backdoors, Ransomware) prove to preserve original attack functionality, and the mean duplication check ratio of malware adversarial samples is below 2.0%. Besides, DeepMal can evade dynamic detectors and be easily enhanced by learning more dynamic features with specific constraints.
The expression profile of circANKRD36 and ANKRD36 as diagnostic biomarkers of chronic kidney disease in patients with type 2 diabetes mellitus
Authors: Rashad Nearmeen M. , Sherif Mohamed H. , El-Shal Amal S. , Abdelsamad Mona A. E.
Published: May 2021

Background

The molecular mechanisms for chronic kidney disease (CKD) remain largely unknown and appear to be multifactorial. In the current study, we aimed to study the circulatory levels of circular ankyrin repeat domain 36 (circANKRD36) and ANKRD36 in Egyptian patients with type 2 diabetes mellitus (T2DM) and CKD and to explore their associations with the progression of CKD. This cross-sectional controlled study enrolled 60 patients with T2DM and 40 controls. Real-time polymerase chain reaction (RT-PCR) and real-time quantitative PCR (RT-qPCR) analyses were used to detect the expression levels of circANKRD36 and ANKRD36.

Results

Our results detected that the relative expression levels of circANKRD36 and ANKRD36 were significantly higher in patients with T2DM compared to controls. CircANKRD36 and ANKRD36 were significantly overexpressed in patients with macroalbuminuria (0.2316±0.096, 0.0086±0.0035, respectively) compared microalbuminuria (0.1347±0.032, 0.0037±0.0008, respectively) as well as normoalbuminuria (0.1261±0.018, 0.0027±0.0004, respectively), p˂0.001*.

Conclusion

The relative expression levels of circANKRD36 and ANKRD36 were significantly increased in patients with T2DM more specifically in patients with diabetic nephropathy (DN) and macroalbuminuria.
EGFR Inhibitors Plus Bevacizumab are Superior Than EGFR Inhibitors Alone as First-Line Setting in Advanced NSCLC With EGFR Mutations and BIM Deletion Polymorphisms (BIM-CLICaP)
Authors: Cardona Andrés F. , Ordóñez-Reyes Camila , Ruiz-Patiño Alejandro , Garcia-Robledo Juan Esteban , Barron Lucia Zatarain , Recondo Gonzalo , Rojas Leonardo , Corrales Luis , Martín Claudio , Barrón Feliciano , Sotelo Carolina , Rodríguez July , Ricaurte Luisa , Rolfo Christian , Ávila Jenny , Mayorga Diana , Archila Pilar , Otero Jorge , Mas Luis , Bermudez Maritza , Gamez Tatiana , Carranza Hernán , Vargas Carlos , Rosell Rafael , Arrieta Oscar
Published: May 2021

PURPOSE

BIM activation is essential for epidermal growth factor receptor ( EGFR)-tyrosine kinase inhibitor (TKI)–triggered apoptosis in EGFR-mutant non–small-cell lung cancer (NSCLC). A deletion in the intron two of the BIM gene results in generation of alternatively spliced isoforms that impairs their apoptotic response to TKIs, conferring the NSCLC cells intrinsic resistance to these medications. Patients with both alterations have poor clinical evolution. The current study aimed to investigate the clinical efficacy and tolerability of EGFR-TKIs plus bevacizumab (Bev) versus EGFR-TKIs alone as first-line treatment in advanced NSCLC patients with EGFR mutations and BIM deletions ( BIMdel).

MATERIALS AND METHODS

A retrospective analysis was conducted. BIMdel was detected using polymerase chain reaction analysis and direct sequencing of DNA. BIM protein expression was investigated by immunohistochemistry, and BIM mRNA levels by reverse transcriptase-polymerase chain reaction. Clinical characteristics, overall survival, progression-free survival (PFS), overall response rate (ORR), and treatment-related adverse events were compared between both groups.

RESULTS

Thirty-three patients were included; 15 received EGFR-TKIs, and 18 received EGFR-TKIs plus Bev. The median age was 63 years, with a majority of recruited female patients. All included individuals had an Eastern Cooperative Oncology Group performance score of 2 or less. The addition of Bev resulted in a significantly higher ORR (94.4% v 40%, P > .001). Median PFS was longer with the use of the combination therapy (11.12 v 7.87 months; P = .001). Median overall survival tended to be longer in the EGFR-TKIs plus Bev (30.9 v 25.4 months; P = .06) but failed to reach statistical significance. Response in terms of both partial and complete as well as overall favorably affected PFS.

CONCLUSION

EGFR-TKIs plus Bev conferred a significantly higher ORR and PFS in advanced NSCLC patients with EGFR mutation and BIMdel. Further prospective studies are needed to validate these findings.
Standard Model and 4-groups
Authors: Miković A. , Vojinović M.
Published: May 2021

We show that a categorical generalization of the the Poincaré symmetry which is based on the n-crossed modules becomes natural and simple when n = 3 and that the corresponding 3-form and 4-form gauge fields have to be a Dirac spinor and a Lorentz scalar, respectively. Hence by using a Poincaré 4-group we naturally incorporate fermionic and scalar matter into the corresponding 4-connection. The internal symmetries can be included into the 4-group structure by using a 3-crossed module based on the

group, so that for

we can include the Standard Model into this categorification scheme.
Influence of gluon behavior on heavy-quark pair production
Authors: Boroun G. R. , Rezaei B.
Published: May 2021

We check the impact of the gluon distribution due to the number of active flavor employed in the calculation of heavy-quark deep-inelastic scattering (DIS) electro-production on the reduced cross-section and structure functions determined in the leading-order (LO) and next-to-leading-order (NLO) quantum chromodynamics (QCD) analysis using the Hadron Electron Ring Accelerator (HERA) combined data. The charm and beauty structure functions are determined and compared with the HERA combined data. The results are in good agreement with respect to the experimental data. We also compare the obtained charm and bottom structure functions with the results from CTEQ6.6 (CTEQ Collaboration (Nadolsky P. M.
et al.), Phys. Rev. D, 78 (2008) 013004) and NNPDF3.1 (NNPDF Collaboration (Ball R. D.
et al.), Eur. Phys. J. C, 77, (2017) 663) parameterization models. The effect of gluon density on these calculations depends on the number of active flavor at asymptotical values of the momentum transfer Q
2. Also, in the HERA kinematic range, the ratios

and

are obtained. These results and comparison with the HERA combined data demonstrate that the suggested method can be applied in the analysis of new colliders.
Sex Differences in the Effect of Testosterone on Adipose Tissue Insulin Resistance From Overweight to Obese Adults
Authors: Li Xiaohui , Liu Jia , Zhou Biao , Li Yinhui , Wu Zhengyu , Meng Hua , Wang Guang
Published: May 2021

Objective

Adipose tissue distribution and glucose metabolism differ between men and women. Few studies have investigated sex differences in adipose tissue insulin resistance (adipose-IR). Herein, we investigated sex differences in adipose-IR in adults ranging from overweight to obese and the potential factors associated with sex differences in adipose-IR.

Methods

A total of 424 adults had their body mass index (BMI), adipose-IR, and sex hormones evaluated. Based on BMI, males and females were assigned to 4 groups.

Results

In total, males (n = 156) had higher adipose-IR than females with similar BMI levels (n = 268) (P < 0.05). Adipose-IR progressively increased from overweight to class III obesity in both males and females (all P < 0.0001); however, only in the class III obesity group was the adipose-IR significantly higher in males than in females (P = 0.025). There were significant differences in testosterone between males and females (all P < 0.01); testosterone levels were negatively correlated with adipose-IR (r = -0.333, P < 0.001) in males but positively correlated with adipose-IR (r = 0.216, P < 0.001) in females. For the logistic regression analysis, testosterone was an independent protective factor against adipose-IR in males, with an odds ratio of 0.858 (B = -0.153 [95% CI, 0.743-0.991], P = 0.037).

Conclusions

Adipose-IR reflects the progressive deterioration in adipose tissue insulin sensitivity from overweight to obesity in both males and females. Males with class III obesity have more severe adipose-IR than similarly obese females. The sex difference is associated with testosterone, and low testosterone levels may contribute to more severe adipose-IR in obese males.
Clinical and Genetic Analysis of KATP Variants With Heart Failure Risk in Patients With Decreased Serum ApoA-I Levels
Authors: Liu Cheng , Lai Yanxian , Pei Jingxian , Huang Huiling , Zhan Junfang , Ying Songsong , Shen Yan
Published: May 2021

Context

Lower serum concentration of apolipoprotein A-I (ApoA-I) is causally associated with heart failure (HF) risk. Adenosine triphosphate–sensitive potassium channels (KATP), as gating channels coupling vascular reactivity and metabolism with ischemic protection, become a new potential target of management for HF. The KATP gene sequence is highly polymorphic and has a high degree of genetic heterogeneity.

Objective

This work aimed to determine whether KATP variants predict the risks of decreased ApoA-I concentration and its related HF.

Methods

A total of 634 individuals, including 317 patients with decreased ApoA-I concentration (< 120 mg/dL) and 317 counterpart participants (≥ 120 mg/dL), were retrospectively selected. Five KATP variants were genotyped through the MassARRAY platform. Exosome-derived microRNAs (exo-miRs) expression profiles were identified by next-generation sequencing, and the top 10 differentially expressed (DE) exo-miRs were verified using quantitative polymerase chain reaction in a validation cohort of 240 individuals with decreased ApoA-I concentration.

Results

KATP rs141294036 was related to an increased risk of lower ApoA-I levels (adjusted odds ratio [OR] = 1.95, P = .002) and HF incidence (adjusted OR = 2.38, P = .009), especially heart failure with preserved ejection fraction (HFpEF; adjusted OR = 2.13, P = .015). After a median 48.6-month follow-up, participants carrying the CC genotype of rs141294036 were associated with an elevated HF rehospitalization risk (adjusted hazard ratio = 1.91, P = .005). Thirty-six exo-miRs were significantly DE between different genotypes of rs141294036 in participants with lower ApoA-I levels, but only 5 exo-miRs (miR-31-5p, miR-126-5p, miR-106a-5p, miR-378i, and miR-181c-5p) were further confirmed.

Conclusion

KATP rs141294036 was associated with increased risks of lower ApoA-I levels, HF incidence (especially HFpEF), and HF rehospitalization in those with the 5 confirmed exo-miRs and its related metabolic pathways.