bluuebunny/crossref_metadata_2025 huggingface dataset:
New approaches to symptomatic treatments for Alzheimer’s disease
Authors: Cummings Jeffrey
Published: January 2021

Background

Successful development of agents that improve cognition and behavior in Alzheimer’s disease (AD) is critical to improving the lives of patients manifesting the symptoms of this progressive disorder.

Discussion

There have been no recent approvals of cognitive enhancing agents for AD. There are currently 6 cognitive enhancers in Phase 2 trials and 4 in phase 3. They represent a variety of novel mechanisms. There has been progress in developing new treatments for neuropsychiatric symptoms in AD with advances in treatment of insomnia, psychosis, apathy, and agitation in AD. There are currently 4 AD-related psychotropic agents in Phase 2 trials and 7 in Phase 3 trials. Many novel mechanisms are being explored for the treatment of cognitive and behavioral targets. Progress in trial designs, outcomes measures, and population definitions are improving trial conduct for symptomatic treatment of AD.

Conclusions

Advances in developing new agents for cognitive and behavioral symptoms of AD combined with enhanced trial methods promise to address the unmet needs of patients with AD for improved cognition and amelioration of neuropsychiatric symptoms.
A qualitative study on health care providers’ experiences of providing comprehensive abortion care in Cox’s Bazar, Bangladesh
Authors: Persson Maria , Larsson Elin C. , Islam Noor Pappu , Gemzell-Danielsson Kristina , Klingberg-Allvin Marie
Published: January 2021

Background

Humanitarian settings are characterised by limited access to comprehensive abortion care. At the same time, humanitarian settings can increase the vulnerability of women and girls to unintended pregnancies and unsafe abortions. Humanitarian actors and health care providers can play important roles in ensuring the availability and accessibility of abortion-related care. This study explores health care providers’ perceptions and experiences of providing comprehensive abortion care in a humanitarian setting in Cox’s Bazar, Bangladesh and identifies barriers and facilitators in service provision.

Method

In-depth interviews (n = 24) were conducted with health care providers (n = 19) providing comprehensive abortion care to Rohingya refugee women and with key informants (n = 5), who were employed by an organisation involved in the humanitarian response. Data were analysed using an inductive content analysis approach.

Results

The national menstrual regulation policy provided a favourable legal environment and facilitated the provision of comprehensive abortion care, while the Mexico City policy created organisational barriers since it made organisations unable or unwilling to provide the full comprehensive abortion care package. Supplies were available, but a lack of space created a barrier to service provision. Although training from organisations had made the health care providers confident and competent and had facilitated the provision of services, their knowledge of the national abortion law and menstrual regulation policy was limited and created a barrier to comprehensive abortion services. Even though the health care providers were willing to provide comprehensive abortion care and had acquired skills and applied strategies to communicate with and provide care to Rohingya women, their personal beliefs and their perceptions of Rohingya women influenced their provision of care.

Conclusion

The availability and accessibility of comprehensive abortion care was limited by unfavourable abortion policies, a lack of privacy, a lack of knowledge of abortion laws and policies, health care providers’ personal beliefs and a lack of cultural safety. To ensure the accessibility and availability of quality services, a comprehensive approach to sexual and reproductive health and rights is needed. Organisations must ensure that health care providers have knowledge of abortion policies and the ability to provide quality care that is woman-centred and non-judgmental.
Observations on the use of Bruton’s tyrosine kinase inhibitors in SAR-CoV-2 and cancer
Authors: Benner Brooke , Carson William E.
Published: January 2021

Bruton’s tyrosine kinase (BTK) inhibitors, drugs utilized in cancer, are being repurposed for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) (COVID-19). Recently, BTK inhibitors acalabrutinib and ibrutinib have been found to protect against pulmonary injury in a small group of patients infected with SARS-CoV-2. The high levels of pro-inflammatory cytokines found in the circulation of COVID-19 patients with severe lung disease suggest the involvement of the innate immune system in this process. Understanding the potential mechanism of action of BTK inhibition in SARS-CoV-2 is clearly of importance to determine how acalabrutinib, ibrutinib and possibly other BTK inhibitors may provide protection against lung injury.
Nature and extent of outpatient podiatry service utilisation in people with diabetes undergoing minor foot amputations: a retrospective clinical audit
Authors: Linton Clare , Searle Angela , Hawke Fiona , Tehan Peta Ellen , Chuter Vivienne
Published: January 2021

Background

People with diabetes are at high risk of foot complications that can lead to lower extremity amputations. National standards suggest that early assessment and management by a podiatry led multidisciplinary high‐risk foot clinic (HRFC) helps to reduce complications. This review is a retrospective audit of the Central Coast Local Health District (CCLHD) podiatry department service utilisation in people with diabetes who had undergone a minor foot amputation.

Methods

All people with diabetes who had minor foot amputations in the calendar year 2017 in the CCLHD in New South Wales were identified. Podiatry occasions of service from all podiatry service clinics (e.g. general, orthoses, wound, HRFC) and hospital stays for 12 months prior to, and 12 months, post the minor foot amputation were extracted.

Results

Data on 74 people with diabetes who underwent 85 minor foot amputations were collected. In the 12‐month period leading up to their minor foot amputation less than half, 42% (n=31), of the patients had attended any of the available podiatry service clinics within the CCLHD system. Post‐amputation and discharge from hospital there was an overall rise of 26% in numbers attending all CCLHD podiatry‐ led clinics bringing the total to 68% (51). However, attendance at the HRFC rose by only 2% from 16% (n=12) to 18% n= (13).

Conclusion

This study shows that there was underutilisation of Podiatry Services in the CCLHD in 2017 with some participants not meeting national treatment guidelines for foot health services. Revision of current referral pathways both prior to, during and following hospitalisation and expanding the multidisciplinary HRFC to accommodate the population by providing more accessible locations has since been undertaken to increase service access. Further provision of education to those highlighted to be at high risk has also been implemented.
The variant call format provides efficient and robust storage of GWAS summary statistics
Authors: Lyon Matthew S. , Andrews Shea J. , Elsworth Ben , Gaunt Tom R. , Hemani Gibran , Marcora Edoardo
Published: January 2021

GWAS summary statistics are fundamental for a variety of research applications yet no common storage format has been widely adopted. Existing tabular formats ambiguously or incompletely store information about genetic variants and associations, lack essential metadata and are typically not indexed yielding poor query performance and increasing the possibility of errors in data interpretation and post-GWAS analyses. To address these issues, we adapted the variant call format to store GWAS summary statistics (GWAS-VCF) and developed open-source tools to use this format in downstream analyses. We provide open access to over 10,000 complete GWAS summary datasets converted to this format (https://gwas.mrcieu.ac.uk).
Morphological, molecular and ecological characterization of a native isolate of Steinernema feltiae (Rhabditida: Steinernematidae) from southern Chile
Authors: Flores Patricia , Alvarado Andrea , Lankin Gabriela , Lax Paola , Prodan Simona , Aballay Erwin
Published: January 2021

Background

Steinernema feltiae is an entomopathogenic nematode used in biological control programs with a global distribution. Populations of this species show phenotypic plasticity derived from local adaptation and vary in different traits, such as location and host penetration. The aim of this work was to describe a Chilean isolate of this nematode species, using integrative approaches.

Methods

Nematode morphological and morphometric studies were conducted along with molecular analysis of nuclear genes. The symbiotic bacterium was also identified by sequencing the 16S rRNA gene. Some ecological characteristics were described, including the temperature requirements for the nematode life cycle and the effect of soil water content for optimal reproduction.

Results

Morphometric characterization revealed a large intra-specific variability. The isolate identity was also corroborated with the analysis of nuclear genes. Based on the 16S gene, its symbiont bacteria, Xenorhabdus bovienii, was identified. The lowest, optimal and highest temperatures found to limit the infestation and reproduction on Galleria mellonella were 10, 20 and 30 °C, respectively; the emergence from the host larvae occurred approximately 10 days after inoculation. Differences were observed in offspring, and 120 infective juveniles (IJ)/larva was the most prolific dose at 20 °C. The soil water content did not affect the number of IJ invaders, penetration efficacy and IJ emergence time or offspring per larva, but it caused a delay in achieving full mortality at the permanent wilting point with respect to saturation and field capacity.

Conclusions

For the first time, a Chilean isolate of S. feltiae is described in detail considering morphological, molecular and ecological aspects. The isolate was shown to be efficient in soil containing water, with optimal temperatures ranging from 15 to 25 °C for host infestation and production of an abundant offspring; these characteristics would allow its potential use as control agents in a wide geographical area of the country.

Graphical Abstract
Long-term remission and biologic persistence rates: 12-year real-world data
Authors: Murray Kieran , Turk Matthew , Alammari Yousef , Young Francis , Gallagher Phil , Saber Tajvur , Fearon Ursula , Veale Douglas J.
Published: January 2021

Background

Biologic therapies have greatly improved outcomes in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Yet, our ability to predict long-term remission and persistence or continuation of therapy remains limited. This study explores predictors of remission and persistence of the initial biologic therapy in patients after 12 years. Furthermore, outcomes with adalimumab and etanercept are compared.

Patients and methods

RA and PsA patients were prospectively recruited from a biologic clinic. Outcomes on commencing therapy, at 1 year and 12 years were reviewed. Demographics, medications, morning stiffness, patient global health score, tender and swollen joint counts, antibody status, CRP and HAQ were collected. Outcomes at 1 year and 12 years are reported and predictors of biologic persistence and EULAR-defined remission (DAS28-CRP < 2.6) are examined with univariate and multivariate analysis.

Results

A total of 403 patients (274 RA and 129 PsA) were analysed. PsA patients were more likely to be male, in full-time employment and have completed higher education. PsA had higher remission rates than RA at both 1 year (60.3% versus 34.5%, p < 0.001) and 12 years (91.3% versus 60.6%, p < 0.001). This difference persisted when patients were matched for baseline disease activity (p < 0.001). Biologic continuation rates were high for RA and PsA at 1 year (49.6% versus 58.9%) and 12 years (38.2% versus 52.3%). In PsA, patients starting on etanercept had lower CRP at 12 years (p = 0.041). Multivariate analysis showed 1-year continuation [OR 4.28 (1.28–14.38)] and 1-year low-disease activity [OR 3.90 (95% CI 1.05–14.53)] was predictive of a 12-year persistence. Persistence with initial biologic at 12 years [OR 4.98 (95% CI 1.83–13.56)] and male gender [OR 4.48 (95% CI 1.25–16.01)] predicted 12 year remission.

Conclusions

This is the first study to show better response to biologic therapy in PsA compared to RA at 12 years. Long-term persistence with initial biologic agent was high and was predicted by biologic persistence and low-disease activity at 1 year. Interestingly, PsA patients had higher levels of employment, educational attainment, and long-term remission rates compared to RA patients.
N-linked glycosylation at site 158 of the HA protein of H5N6 highly pathogenic avian influenza virus is important for viral biological properties and host immune responses
Authors: Gao Ruyi , Gu Min , Shi Liwei , Liu Kaituo , Li Xiuli , Wang Xiaoquan , Hu Jiao , Liu Xiaowen , Hu Shunlin , Chen Sujuan , Peng Daxin , Jiao Xinan , Liu Xiufan
Published: January 2021

Since 2014, clade 2.3.4.4 has become the dominant epidemic branch of the Asian lineage H5 subtype highly pathogenic avian influenza virus (HPAIV) in southern and eastern China, while the H5N6 subtype is the most prevalent. We have shown earlier that lack of glycosylation at position 158 of the hemagglutinin (HA) glycoprotein due to the T160A mutation is a key determinant of the dual receptor binding property of clade 2.3.4.4 H5NX subtypes. Our present study aims to explore other effects of this site among H5N6 viruses. Here we report that N-linked glycosylation at site 158 facilitated the assembly of virus-like particles and enhanced virus replication in A549, MDCK, and chicken embryonic fibroblast (CEF) cells. Consistently, the HA-glycosylated H5N6 virus induced higher levels of inflammatory factors and resulted in stronger pathogenicity in mice than the virus without glycosylation at site 158. However, H5N6 viruses without glycosylation at site 158 were more resistant to heat and bound host cells better than the HA-glycosylated viruses. H5N6 virus without glycosylation at this site triggered the host immune response mechanism to antagonize the viral infection, making viral pathogenicity milder and favoring virus spread. These findings highlight the importance of glycosylation at site 158 of HA for the pathogenicity of the H5N6 viruses.
Elevated plasma IL-6 and CRP levels are associated with adverse clinical outcomes and death in critically ill SARS-CoV-2 patients: inflammatory response of SARS-CoV-2 patients
Authors: Lavillegrand Jean-Rémi , Garnier Marc , Spaeth Agathe , Mario Nathalie , Hariri Geoffroy , Pilon Antoine , Berti Enora , Fieux Fabienne , Thietart Sara , Urbina Tomas , Turpin Matthieu , Darrivere Lucie , Fartoukh Muriel , Verdonk Franck , Dumas Guillaume , Tedgui Alain , Guidet Bertrand , Maury Eric , Chantran Yannick , Voiriot Guillaume , Ait-Oufella Hafid
Published: January 2021

Background

SARS coronavirus 2 (SARS-CoV-2) is responsible for high morbidity and mortality worldwide, mostly due to the exacerbated inflammatory response observed in critically ill patients. However, little is known about the kinetics of the systemic immune response and its association with survival in SARS-CoV-2+ patients admitted in ICU. We aimed to compare the immuno-inflammatory features according to organ failure severity and in-ICU mortality.

Methods

Six-week multicentre study (N = 3) including SARS-CoV-2+ patients admitted in ICU. Analysis of plasma biomarkers at days 0 and 3–4 according to organ failure worsening (increase in SOFA score) and 60-day mortality.

Results

101 patients were included. Patients had severe respiratory diseases with PaO2/FiO2 of 155 [111–251] mmHg), SAPS II of 37 [31–45] and SOFA score of 4 [3–7]. Eighty-three patients (83%) required endotracheal intubation/mechanical ventilation and among them, 64% were treated with prone position. IL-1β was barely detectable. Baseline IL-6 levels positively correlated with organ failure severity. Baseline IL-6 and CRP levels were significantly higher in patients in the worsening group than in the non-worsening group (278 [70–622] vs. 71 [29–153] pg/mL, P < 0.01; and 178 [100–295] vs. 100 [37–213] mg/L, P < 0.05, respectively). Baseline IL-6 and CRP levels were significantly higher in non-survivors compared to survivors but fibrinogen levels and lymphocyte counts were not different between groups. After adjustment on SOFA score and time from symptom onset to first dosage, IL-6 and CRP remained significantly associated with mortality. IL-6 changes between Day 0 and Day 3–4 were not different according to the outcome. A contrario, kinetics of CRP and lymphocyte count were different between survivors and non-survivors.

Conclusions

In SARS-CoV-2+ patients admitted in ICU, a systemic pro-inflammatory signature was associated with clinical worsening and 60-day mortality.
Long-term survival with multiple metastasectomies for pulmonary osteosarcoma: a case report
Authors: Takamori Satoshi , Oizumi Hiroyuki , Suzuki Jun , Suzuki Katsuyuki
Published: January 2021

Background

Repeat pulmonary metastasectomy (PM) considerably improves the prognosis of patients with pulmonary metastases of osteosarcoma. Reports have demonstrated a significantly improved prognosis in patients who have undergone repeat metastasectomy for osteosarcoma; however, there have been no reports with more than six metastasectomies. Herein, we describe the long-term survival of a patient following resection of multiple tumors and other treatments for metastatic osteosarcoma.

Case presentation

A 28-year-old woman underwent extensive resection and postoperative adjuvant chemotherapy for right tibial sarcoma. Over the years, she developed repeated pulmonary metastases. First, 116 metastases were removed from the bilateral lungs. After that, multiple PMs of approximately 250 tumors and other treatments for deep metastatic lesions were performed. The patient died of the underlying disease 24 years after the primary surgery.

Conclusions

This case report demonstrates the long-term survival benefit of a multidisciplinary treatment centered on multiple metastasectomies.
High prevalence of pulmonary tuberculosis among female sex workers, men who have sex with men, and transgender women in Papua New Guinea
Authors: Willie Barne , Hakim Avi J. , Badman Steven G. , Weikum Damian , Narokobi Rebecca , Coy Kelsey , Gabuzzi Josephine , Pekon Simon , Gene Samson , Amos Angelyn , Kupul Martha , Hou Parker , Dala Nick M. , Whiley David M. , Wapling Johanna , Kaldor John M. , Vallely Andrew J. , Kelly-Hanku Angela
Published: January 2021

Background

Papua New Guinea (PNG) has a tuberculosis (TB) case notification rate of 333 cases per 100,000 population in 2016 and is one of the 14 countries classified by the World Health Organization (WHO) as “high-burden” for TB, multi-drug-resistant TB (MDR-TB), and TB/HIV. HIV epidemic is mixed with a higher prevalence among key populations, female sex workers (FSW), men who have sex with men (MSM), and transgender women (TGW).

Methods

We conducted a cross-sectional HIV biobehavioral survey (BBS) using respondent-driven sampling method among FSW, MSM, and TGW in Port Moresby, Lae, and Mt. Hagen (2016–2017). As part of the study, participants were screened for the four symptoms suggestive of TB infection using the WHO TB screening algorithm. Sputum and venous whole blood samples were collected and tested for pulmonary TB and HIV infection, respectively. Pulmonary TB testing was performed using GeneXpert®MTB/RIF molecular point-of-care test, and HIV testing was done following the PNG national HIV testing algorithm. All data discussed are weighted unless otherwise mentioned.

Results

Among FSW, 72.6%, 52.0%, and 52.9% in Port Moresby, Lae, and Mt. Hagen, respectively, experienced at least one symptom suggestive of TB infection. Among MSM and TGW, 69% and 52.6% in Port Moresby and Lae, respectively, experienced at least one symptom suggestive of TB infection. Based on GeneXpert®MTB/RIF results, the estimated TB prevalence rate among FSW was 1200, 700, and 200 per 100,000 in Port Moresby, Lae, and Mt. Hagen, respectively. Among MSM and TGW, the estimated TB prevalence rate was 1000 and 1200 per 100,000 in Port Moresby and Lae, respectively. Co-prevalence of TB/HIV among FSW was 0.1% in Port Moresby and 0.2% in Lae. There were no co-prevalent cases among FSW in Mt. Hagen or among MSM and TGW in Port Moresby and Lae.

Conclusions

Key populations have a higher estimated rate of pulmonary TB than the national rate of pulmonary and extra-pulmonary TB combined. This showed that screening key populations for TB should be integrated into HIV programs regardless of HIV status in PNG’s national TB response.
Characterization and typology of goat production systems in Algeria based on producers survey
Authors: Ouchene-Khelifi Nadjet Amina , Ouchene Nassim , Lafri Mohamed
Published: January 2021

Background

Goats, often associated with sheep, are a vital part of the national economy in many countries around the world, and goat farming contributes significantly to the family economy, sustainable livelihoods and poverty reduction. In order to study the goat farming system in Algeria, this study, which started between September 2012 and June 2015, involved 141 farms in 104 villages and 21 wilayas in Algeria.

Results

The results showed that 99.29% of the goats producers were male, most of which (74.47%) were not the owners of the animals. Goat farming represents a main activity for only 18.44% of the farmers surveyed. They are generally found in small numbers often associated with a large sheep herd (78.72%). Of the 141 farms visited, 50.35% use a sedentary farming system, 17.71% practice seasonal transhumance during the dry season (May to October), and 31.91% are semi-sedentary. However, it is worth noting that females (85.82%) are often more numerous than males (14.18%) in the herd. The farm that generally constitutes the shelter is reduced in most cases to a simple pen, without a roof, inside which the animals are enclosed and whose space is delimited by a metal or wooden fence. Hygiene is in the majority of cases poor (57.45%). Most of the farms (78.01%) do not contain goats of the same breed, and crossbreeding is generally not controlled (78.72%) and is very rarely done with bucks of the same breed (14.89%). Most breeders (92.20%) largely neglect the health of their goats compared to sheep.

Conclusion

Finally, the Algerian goat seems to be largely neglected and considered as a secondary species associated with sheep. For this reason, it is mandatory to give more importance to this species. The Algerian government must carry out activities related to the conservation and improvement of breeding systems through the development of breeding programs and ensure the sustainable management of ecosystems used for food production.
Working and short-term memory defects in Egyptian dyslexic children
Authors: Hamouda N. H. , El-Shafaei R. A.
Published: January 2021

Background

Memory is the process of encoding, storing, consolidating, and retrieving information. Short-term memory (STM) describes the process of passively holding small amounts of material to be later produced in an untransformed fashion. Tasks that measure STM typically involve situations that do not vary their initial encoding (recall a sequence of items in the order in which they were presented). In children with dyslexia, deficits in working memory have not been well specified.

Results

There is statistically significant between group I and group II regarding all items of the TOMAL-2.

Conclusions

Dyslexic children are distinctively disadvantaged compared with average readers on working and short term memory tasks.
Finding order within the disorder: a case study exploring the meaningfulness of delusions
Authors: Ritunnano Rosa , Humpston Clara , Broome Matthew R.
Published: January 2021

Can delusions, in the context of psychosis, enhance a person’s sense of meaningfulness? The case described here suggests that, in some circumstances, they can. This prompts further questions into the complexities of delusion as a lived phenomenon, with important implications for the clinical encounter. While assumptions of meaninglessness are often associated with concepts of ‘disorder’, ‘harm’ and ‘dysfunction’, we suggest that meaning can nonetheless be found within what is commonly taken to be incomprehensible or even meaningless. A phenomenological and value-based approach appears indispensable for clinicians facing the seemingly paradoxical coexistence of harmfulness and meaningfulness.
Lenalidomide-Epoetin Alfa Versus Lenalidomide Monotherapy in Myelodysplastic Syndromes Refractory to Recombinant Erythropoietin
Authors: List Alan F. , Sun Zhuoxin , Verma Amit , Bennett John M. , Komrokji Rami S. , McGraw Kathy , Maciejewski Jaroslaw , Altman Jessica K. , Cheema Puneet S. , Claxton David F. , Luger Selina M. , Mattison Ryan J. , Wassenaar Timothy R. , Artz Andrew S. , Schiffer Charles A. , Litzow Mark R. , Tallman Martin S.
Published: January 2021

PURPOSE

Impaired response to erythropoietin underlies ineffective erythropoiesis and anemia in myelodysplastic syndromes (MDS). We investigated whether treatment with lenalidomide (LEN), which augments erythropoietin receptor signaling in vitro, can restore and improve hemoglobin response to epoetin (EPO) alfa in patients with lower-risk, non-del(5q) MDS who have anemia that is refractory to or have low probability of benefit from treatment with recombinant erythropoietin.

METHODS

In a phase III, US intergroup trial, we randomly assigned patients to receive either LEN and EPO alfa or LEN alone following stratification by serum erythropoietin concentration and prior erythropoietin treatment.

RESULTS

A total of 195 evaluable patients were randomly assigned: 99 patients to the LEN-EPO alfa cohort and 96 to LEN alone. After four cycles of treatment, the primary end point of major erythroid response (MER) was significantly higher (28.3%) with the combination compared with LEN alone (11.5%) ( P = .004). Among 136 patients who completed 16 weeks of study treatment, 38.9% and 15.6% achieved MER, respectively ( P = .004). Additionally, minor erythroid response was achieved in 18.2% and 20.8% of patients, for an overall erythroid response rate of 46.5% versus 32.3%. Among LEN nonresponders, 38 crossed over to the addition of EPO alfa with 10 patients (26.3%) achieving a MER. Responses to the combined treatment were highly durable with a median MER duration of 23.8 months compared with 13 months with LEN alone.

CONCLUSION

LEN restores sensitivity to recombinant erythropoietin in growth factor–insensitive, lower-risk, non-del(5q) MDS, to yield a significantly higher rate and duration of MER compared with LEN alone (funded by the National Cancer Institute; E2905 ClinicalTrials.gov identifier: NCT02048813 ).
Correlation between two quantum concepts within shape phase transitions in nuclei
Authors: Ait El Korchi S. , Chabab M. , El Batoul A. , Lahbas A. , Oulne M.
Published: January 2021

The present work consists in studying a correlation that we have observed, for the first time, between two well-known quantum concepts, namely: the Minimal Length (ML) and the Deformation-Dependent Mass (DDM) which are widely used in different fields of physics. This correlation was revealed in transitional nuclei near the Critical Point Symmetries (CPS) X(3) and Z(4) through calculations of their energy spectra, moments of inertia and transition probabilities. Based on this correlation which could be considered as a new signature for CPS, we have found eventual new candidate nuclei for these critical points.
Multifunctional Applications of Engineered Extracellular Vesicles in the Treatment of Cancer
Authors: Kugeratski Fernanda G , McAndrews Kathleen M , Kalluri Raghu
Published: January 2021

Extracellular vesicles (EVs) are key players of intercellular communication in the physiological and pathological setting. In cancer, EVs mediate complex signaling mechanisms between cancer cells and the tumor microenvironment (TME), and can influence tumor progression and the response to existing therapies. Importantly, EVs can be loaded with therapeutic agents and modified to display tumor-targeting molecules. In the field of nanomedicine, EVs have been engineered to serve as therapeutic delivery vehicles for several anticancer agents, including antibodies, chemotherapy, compounds, CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats–associated endonuclease 9), and small interfering RNA (siRNA). Notably, the engineered EVs were shown to suppress malignant features of cancer cells, to elicit antitumor immunity, and to decrease tumor angiogenesis. Here, we review the EV-based therapies designed to target cancer cells and to educate components of the TME to drive antitumor responses. These studies illustrate the multifunctional applications of EVs in the development of anticancer therapies and their translational potential for cancer treatment.
lncRNAs in development and differentiation: from sequence motifs to functional characterization
Authors: Constanty Florian , Shkumatava Alena
Published: January 2021

The number of long noncoding RNAs (lncRNAs) with characterized developmental and cellular functions continues to increase, but our understanding of the molecular mechanisms underlying lncRNA functions, and how they are dictated by RNA sequences, remains limited. Relatively short, conserved sequence motifs embedded in lncRNA transcripts are often important determinants of lncRNA localization, stability and interactions. Identifying such RNA motifs remains challenging due to the substantial length of lncRNA transcripts and the rapid evolutionary turnover of lncRNA sequences. Nevertheless, the recent discovery of specific RNA elements, together with their experimental interrogation, has enabled the first step in classifying heterogeneous lncRNAs into sub-groups with similar molecular mechanisms and functions. In this Review, we focus on lncRNAs with roles in development, cell differentiation and normal physiology in vertebrates, and we discuss the sequence elements defining their functions. We also summarize progress on the discovery of regulatory RNA sequence elements, as well as their molecular functions and interaction partners.
Tactile active sensing in an insect plant pollinator
Authors: Deora Tanvi , Ahmed Mahad A. , Daniel Thomas L. , Brunton Bing W.
Published: January 2021

The interaction between insects and the flowers they pollinate has driven the evolutionary diversity of both insects and flowering plants, two groups with the most numerous species on Earth. Insects use vision and olfaction to localize host plants, but we know relatively little about how they find the tiny nectary opening in the flower, which can be well beyond their visual resolution. Especially when vision is limited, touch becomes crucial in successful insect–plant pollination interactions. Here, we studied the remarkable feeding behavior of crepuscular hawkmoths Manduca sexta, which use their long, actively controlled, proboscis to expertly explore flower-like surfaces. Using machine vision and 3D-printed artificial flower-like feeders, we revealed a novel behavior that shows moths actively probe surfaces, sweeping their proboscis from the feeder edge to its center repeatedly until they locate the nectary opening. Moreover, naive moths rapidly learn to exploit these flowers, and they adopt a tactile search strategy to more directly locate the nectary opening in as few as three to five consecutive visits. Our results highlight the proboscis as a unique active sensory structure and emphasize the central role of touch in nectar foraging insect–plant pollinator interactions.
Development of Molecular Transformations on the Basis of Catalytic Generation of Anionic Species by Organosuperbase
Authors: Kondoh Azusa , Terada Masahiro
Published: January 2021

In this account, we summarized our recent efforts to develop molecular transformations under Brønsted base catalysis on the basis of our own guiding principles for designing reaction systems, that include “the generation and application of anionic species which are difficult to utilize in conventional reaction systems” and “the employment of organosuperbases possessing much higher basicities than conventional organic bases as a catalyst”. In particular, we discussed reactions involving the generation of carbanions of less acidic compounds through the formal umpolung process from carbonyl compounds and formal [3+2] cycloadditions involving the generation of the synthetic equivalent of a 1,3-dipole through epoxide opening.
Resistance Training Load Effects on Muscle Hypertrophy and Strength Gain: Systematic Review and Network Meta-analysis
Authors: LOPEZ PEDRO , RADAELLI RÉGIS , TAAFFE DENNIS R. , NEWTON ROBERT U. , GALVÃO DANIEL A. , TRAJANO GABRIEL S. , TEODORO JULIANA L. , KRAEMER WILLIAM J. , HÄKKINEN KEIJO , PINTO RONEI S.
Published: January 2021

Purpose

This study aimed to analyze the effect of resistance training (RT) performed until volitional failure with low, moderate, and high loads on muscle hypertrophy and muscle strength in healthy adults and to assess the possible participant-, design-, and training-related covariates that may affect the adaptations.

Methods

Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, MEDLINE, CINAHL, EMBASE, SPORTDiscus, and Web of Science databases were searched. Including only studies that performed sets to volitional failure, the effects of low- (>15 repetitions maximum (RM)), moderate- (9–15 RM), and high-load (≤8 RM) RTs were examined in healthy adults. Network meta-analysis was undertaken to calculate the standardized mean difference (SMD) between RT loads in overall and subgroup analyses involving studies deemed of high quality. Associations between participant-, design-, and training-related covariates with SMD were assessed by univariate and multivariate network meta-regression analyses.

Results

Twenty-eight studies involving 747 healthy adults were included. Although no differences in muscle hypertrophy between RT loads were found in overall (P = 0.113–0.469) or subgroup analysis (P = 0.871–0.995), greater effects were observed in untrained participants (P = 0.033) and participants with some training background who undertook more RT sessions (P = 0.031–0.045). Muscle strength improvement was superior for both high-load and moderate-load compared with low-load RT in overall and subgroup analysis (SMD, 0.60–0.63 and 0.34–0.35, respectively; P < 0.001–0.003), with a nonsignificant but superior effect for high compared with moderate load (SMD, 0.26–0.28, P = 0.068).

Conclusions

Although muscle hypertrophy improvements seem to be load independent, increases in muscle strength are superior in high-load RT programs. Untrained participants exhibit greater muscle hypertrophy, whereas undertaking more RT sessions provides superior gains in those with previous training experience.
Recovery from Achilles Tendon Repair: A Combination of Postsurgery Outcomes and Insufficient Remodeling of Muscle and Tendon
Authors: STÄUDLE BENJAMIN , SEYNNES OLIVIER , LAPS GUIDO , GÖLL FABIAN , BRÜGGEMANN GERT-PETER , ALBRACHT KIRSTEN
Published: January 2021

Introduction

Achilles tendon rupture (ATR) patients have persistent functional deficits in the triceps surae muscle–tendon unit (MTU). The complex remodeling of the MTU accompanying these deficits remains poorly understood. The purpose of the present study was to associate in vivo and in silico data to investigate the relations between changes in MTU properties and strength deficits in ATR patients.

Methods

Eleven male subjects who had undergone surgical repair of complete unilateral ATR were examined 4.6 ± 2.0 (mean ± SD) yr after rupture. Gastrocnemius medialis (GM) tendon stiffness, morphology, and muscle architecture were determined using ultrasonography. The force–length relation of the plantar flexor muscles was assessed at five ankle joint angles. In addition, simulations (OpenSim) of the GM MTU force–length properties were performed with various iterations of MTU properties found between the unaffected and the affected side.

Results

The affected side of the patients displayed a longer, larger, and stiffer GM tendon (13% ± 10%, 105% ± 28%, and 54% ± 24%, respectively) compared with the unaffected side. The GM muscle fascicles of the affected side were shorter (32% ± 12%) and with greater pennation angles (31% ± 26%). A mean deficit in plantarflexion moment of 31% ± 10% was measured. Simulations indicate that pairing an intact muscle with a longer tendon shifts the optimal angular range of peak force outside physiological angular ranges, whereas the shorter muscle fascicles and tendon stiffening seen in the affected side decrease this shift, albeit incompletely.

Conclusions

These results suggest that the substantial changes in MTU properties found in ATR patients may partly result from compensatory remodeling, although this process appears insufficient to fully restore muscle function.
Digital Talent Capability Model for Transforming Technology-Based Holding Companies
Authors:   PT Telekomunikasi Indonesia, Tbk - School of Business and Management / Bandung Institue of Technology (ITB) Indonesia Indonesia, Fahmi Tubagus Arief , Tjakraatmadja Jann Hidajat ,   School of Business and Management / Bandung Institue of Technology (ITB) Indonesia, Ginting Henndy
Published: January 2021

Abstract. Digital transformation is inevitable for organizations to remain competitive in the current business landscape. In reality, organizations rely heavily on their human capabilities to achieve digital transformation goals. However, most studies have neglected this dynamic component and have focused instead on organizational readiness. This study strives to fill such a research gap by uncovering digital talent capabilities that could accelerate digital transformation. We propose a conceptual model based on a literature review and enriched by qualitative research in a representative Telecommunication Company. The conceptual model highlights attitudes to change as a critical factor in transforming individual capability towards digital transformation. The model also explains how culture and digital literacy can positively relate to digital talents’ attitudes towards change and performance. Besides giving theoretical contributions to support the literature, the study’s outcomes can be utilized by organizations intending to transform their human capitals’ digital capabilities. Although there is still a possibility of real behavior arising from individual problem-solving habits, the paper ends with some recommendations, stressing the need for future empirical work. Keywords: Attitudes to Change, Culture, Digital Literacy, Digital Talent Capability, Performance
Inventory Level Improvement in Pharmacy Company Using Probabilistic EOQ Model and Two Echelon Inventory: A Case Study
Authors:   School of Business Management, Institut Teknologi Bandung, Indonesia, Farmaciawaty Desy Anisya , Basri Mursyid Hasan , Utama Akbar Adhi , Widjaja Fransisca Budyanto , Rachmania Ilma Nurul
Published: January 2021

Abstract. This research is aimed to maintain the inventory level in a two-echelon pharmacy company. The company is a pharmacy company that has 16 branches that operate in Bandung and the surrounding area. The company has a problem with its high inventory cost. To solve the problem, the authors compare two methods that suit the company condition, i.e., the decentralized system using probabilistic EOQ model and the centralization system using the multi-echelon inventory technique. We analyzed sales data and on-hand inventory data acquired from the company information system to perform the study. We limit the scope to the class A items only. We also assume the lead time, setup cost, and holding cost used in this study with the company's owner's consent. To conclude, using the decentralized system, the company will save 31% of their inventory cost, while using the centralization system with the multi-echelon technique, the company will be able to save 61% of their inventory cost. We recommend the company to refer to its competitive strategy before deciding which model it would be implemented. Keywords: Centralization, Decentralization, Probabilistic Economic Order Quantity (EOQ), Multi-Echelon Inventory, Pharmaceutical Inventory Management
The Factors that Determine Interest to Use of Mobile Payment: Study on the Students of Garut University, Indonesia
Authors:   Faculty of Social and Political Sciences, Garut University , Indonesia, Ramdhani Abdullah , Alamanda Dini Turipanam ,   Faculty of Economics, Garut University, Indonesia, Harisana Muhammad Husna , Akbar Gugun Geusan
Published: January 2021

Abstract. Mobile payment is generally a payment tool in the form of software available in smartphones to make it easier for its users to make transactions anytime and anywhere his research aims to give empirical evidence of the influence of perceived ease of use, perceived usefulness, trust, and security on the interest in the use of mobile payment in Garut University students. We collect questionnaires from 100 students that are selected using the proportionate sampling method. The data is then analyzed using multiple linear regression. The analysis’ results show that both perceived of benefit and security variables partially has a positive effect while the perceived ease of use and trust has an insignificant effect on the interest in using mobile payments. This study provides an essential insight into how academic users in rural areas in Indonesia adopt electronic payment technologies. Keywords: Perceived ease of use, Perceived of usefulness, Trust, Security, Interests.
Isolated low toe–brachial index is associated with increased mortality and morbidity: a retrospective cohort study
Authors: Manu Chris Adusei , Slim Hani , Huang Dean , Wilkins Christopher Jason , Vas Prashanth R Joseph , Rashid Hisham , Winkley Kirsty , Edmonds Michael
Published: January 2021

Objective:

The aim was to assess the prognostic impact of perfusion assessments including ankle–brachial Index (ABI) and toe–brachial Index (TBI) on survival of patients who present with diabetic foot ulceration and to analyse clinical outcomes when patients are categorised into three levels of limb ischaemia.

Method:

This was a retrospective cohort analysis of consecutive patients presenting with foot ulceration. Patients continued with their standard of care, after having baseline assessments of limb perfusion. Patients were retrospectively categorised into three groups according to baseline ABI and TBI: Group 1 (n=31) non-ischaemic (TBI≥0.75, ABI≥0.9), Group 2 (n=67) isolated low TBI with foot ischaemia (TBI<0.75, ABI≥0.90) and Group 3 (n=30) foot–leg ischaemia (TBI<0.75, ABI<0.90).

Results:

A total of 128 patients took part in the study. Low TBI was associated with a significant decrease in patient survival (42±20 versus 51±16 months, p=0.011). There was a progressive and significant decline in mean patient survival time (51±16 versus 44±20 versus 39±22 months, respectively, for ANOVA across the three groups, p=0.04). Patients with isolated low TBI had angioplasty and bypass at a rate similar to that of patients in Group 3 (low ABI and low TBI). The proportion of angioplasties was significantly higher in the isolated low TBI (19.4% (13/67) versus the non-ischaemic 3.2% (1/31), p=0.033). Such revascularisation resulted in ulcer healing within the foot ischaemic group that was similar to the non-ischaemic group (68% versus 60% over 12 months, p=0.454).

Conclusion:

Regardless of ABI level, measurement of TBI identifies patients with isolated low TBI who require specialised care pathways and revascularisation to achieve ulcer healing that is similar to non-ischaemic patients.
The Evolution of the “Catalan Health Model” in the Twentieth Century. Sources for its Study
Authors: Sabaté Ferran
Published: January 2021

This paper presents an overview of relevant sources for the study of the development of the “Catalan Health Model” during the twentieth century, and the ideas and institutions influencing its evolution. The paper indicates that it is a health system configuration where the core is public universal health assistance, complemented by the private health sector. Also, that it is the result of a dynamic traditional mixed model organization. The sources for the study of this health system are scattered in public or private archives and published reports. Due to the disruptions of war and periods of dictatorship, the model has gaps or becomes disjointed.
Second harmonic generation and wavefront shaping in dielectric metasurfaces
Authors: Gigli Carlo , Marino Giuseppe , Artioli Alberto , Claudon Julien , Rocco Davide , De Angelis Costantino , Gerard Jean-Michel , Leo Giuseppe
Published: January 2021

We demonstrate an AlGaAs metasurface that implements second harmonic generation with engineered phase-front. Nonlinear holography is obtained, with three-order-of-magnitude higher conversion efficiency than in χ(3) plasmonic metasurfaces.
Switching Quantum Interference with Phase-change Reconfigurable Metasurfaces
Authors: Estakhri Nooshin M. , Norris Theodore B.
Published: January 2021

We show how a metasurface incorporating a thermally controlled phase-change material (i.e. GeTe) can enable tunable quantum interference, switching between coalescence and anti-coalescence.
All-optical multilevel switching of GST metasurface
Authors: Choi Chulsoo , Sung Jangwoon , Lee Byoungho
Published: January 2021

Ge2Sb2Te5 (GST) has bi-stable phases, so called amorphous and crystalline phase. It can be reversibly switched within nanosecond time scale through applying thermal bias. We introduce a method to expand GST metasurface’s switching functionality to three levels.
Holographic phase imaging to observe intracellular dynamics of plant cells during dehydration
Authors: Wang Zhe , Bianco Vittorio , Pirone Daniele , Memmolo Pasquale , Paturzo Melania , Ferraro Pietro
Published: January 2021

We show that dehydrating process can be effective for improving the phase-contrast in bioimaging, thus permitting a better observation of plant cells with the scope of learning more about cellular dynamics.
Robust Topology Optimization of Foundry-Manufacturable Photonic Devices: An Open-Source FDTD Toolbox
Authors: Hammond Alec M. , Oskooi Ardavan , Johnson Steven G. , Ralph Stephen E.
Published: January 2021

Integrated photonic foundries require development kits composed of compact, robust, broadband, 3D devices. We report on a novel, open-source density-based topology optimization framework that reliably designs devices to meet these stringent criteria.
Long-term Hybrid Stabilization of CEP
Authors: Hirschman Jack , Lemons Randy , Chansky Evan , Steinmeyer Günter , Carbajo Sergio
Published: January 2021

Controlling the CEP in mode-locked lasers over long timescales is crucial for real-world applications. We present a hybrid stabilization system in an Er: Yb:glass mode-locked laser with 75 hours of stabilization and IPN below 14 mrad.
Optical Biosensor for in situ metabolite quantification in plant leaves
Authors: Montero-Oleas Andrea , Costa-Vera Cesar , Leon Briggitte , Mendez Miguel Angel , de Lourdes Torres María
Published: January 2021

We present a strategy based on the optical properties of the G-cuadruplex DNA-bound NMM IX dye to successfully quantify plant metabolites. As a proof of concept, we quantify the caffeine metabolite from Ilex guayusa leaves. Comments and questions should be directed to the OSA Conference Papers staff (tel: +1 202.416.6191, e-mail: cstech@osa.org).
Designing Silicon Nanoparticles for Optical Bioimaging
Authors: Zabotnov Stanislav , Golovan Leonid , Kurakina Daria , Khilov Aleksandr , Sokolovskaya Olga , Skobelkina Anastasiia , Kashaev Fedor , Kashkarov Pavel , Sergeeva Ekaterina , Kirillin Mikhail
Published: January 2021

We report on developing a technique for fabricating silicon nanoparticles by laser ablation of porous silicon and silicon nanowires in liquids that have potential for image contrasting in fluorescence imaging and optical coherence tomography.