bluuebunny/crossref_metadata_2025 huggingface dataset:
In vitro-in vivo correlations of pulmonary inflammogenicity and genotoxicity of MWCNT
Authors: Di Ianni Emilio , Erdem Johanna Samulin , Møller Peter , Sahlgren Nicklas Mønster , Poulsen Sarah Søs , Knudsen Kristina Bram , Zienolddiny Shan , Saber Anne Thoustrup , Wallin Håkan , Vogel Ulla , Jacobsen Nicklas Raun
Published: July 2021

Background

Multi-walled carbon nanotubes (MWCNT) have received attention due to extraordinary properties, resulting in concerns for occupational health and safety. Costs and ethical concerns of animal testing drive a need for in vitro models with predictive power in respiratory toxicity. The aim of this study was to assess pro-inflammatory response (Interleukin-8 expression, IL-8) and genotoxicity (DNA strand breaks) caused by MWCNT with different physicochemical properties in different pulmonary cell models and correlate these to previously published in vivo data. Seven MWCNT were selected; two long/thick (NRCWE-006/Mitsui-7 and NM-401), two short/thin (NM-400 and NM-403), a pristine (NRCWE-040) and two surface modified; hydroxylated (NRCWE-041) and carboxylated (NRCWE-042). Carbon black Printex90 (CB) was included as benchmark material. Human alveolar epithelial cells (A549) and monocyte-derived macrophages (THP-1a) were exposed to nanomaterials (NM) in submerged conditions, and two materials (NM-400 and NM-401) in co-cultures of A549/THP-1a and lung fibroblasts (WI-38) in an air-liquid interface (ALI) system. Effective doses were quantified by thermo-gravimetric-mass spectrometry analysis (TGA-MS). To compare genotoxicity in vitro and in vivo, we developed a scoring system based on a categorization of effects into standard deviation (SD) units (< 1, 1, 2, 3 or 4 standard deviation increases) for the increasing genotoxicity.

Results

Effective doses were shown to be 25 to 53%, and 21 to 57% of the doses administered to A549 and THP-1a, respectively. In submerged conditions (A549 and THP-1a cells), all NM induced dose-dependent IL-8 expression. NM-401 and NRCWE-006 caused the strongest pro-inflammatory response. In the ALI-exposed co-culture, only NM-401 caused increased IL-8 expression, and no DNA strand breaks were observed. Strong correlations were found between in vitro and in vivo inflammation when doses were normalized by surface area (also proxy for diameter and length). Significantly increased DNA damage was found for all MWCNT in THP-1a cells, and for short MWCNT in A549 cells. A concordance in genotoxicity of 83% was obtained between THP-1a cells and broncho-alveolar lavaged (BAL) cells.

Conclusion

This study shows correlations of pro-inflammatory potential in A549 and THP-1a cells with neutrophil influx in mice, and concordance in genotoxic response between THP-1a cells and BAL cells, for seven MWCNT.
The LORIS MyeliNeuroGene rare disease database for natural history studies and clinical trial readiness
Authors: Spahr Aaron , Rosli Zaliqa , Legault Mélanie , Tran Luan T. , Fournier Simon , Toutounchi Helia , Darbelli Lama , Madjar Cécile , Lucia Cassandra , St-Jean Marie-Lou , Das Samir , Evans Alan C. , Bernard Geneviève
Published: July 2021

Background

Rare diseases are estimated to affect 150–350 million people worldwide. With advances in next generation sequencing, the number of known disease-causing genes has increased significantly, opening the door for therapy development. Rare disease research has therefore pivoted from gene discovery to the exploration of potential therapies. With impending clinical trials on the horizon, researchers are in urgent need of natural history studies to help them identify surrogate markers, validate outcome measures, define historical control patients, and design therapeutic trials.

Results

We customized a browser-accessible multi-modal (e.g. genetics, imaging, behavioral, patient-determined outcomes) database to increase cohort sizes, identify surrogate markers, and foster international collaborations. Ninety data entry forms were developed including family, perinatal, developmental history, clinical examinations, diagnostic investigations, neurological evaluations (i.e. spasticity, dystonia, ataxia, etc.), disability measures, parental stress, and quality of life. A customizable clinical letter generator was created to assist in continuity of patient care.

Conclusions

Small cohorts and underpowered studies are a major challenge for rare disease research. This online, rare disease database will be accessible from all over the world, making it easier to share and disseminate data. We have outlined the methodology to become Title 21 Code of Federal Regulations Part 11 Compliant, which is a requirement to use electronic records as historical controls in clinical trials in the United States. Food and Drug Administration compliant databases will be life-changing for patients and families when historical control data is used for emerging clinical trials. Future work will leverage these tools to delineate the natural history of several rare diseases and we are confident that this database will be used on a larger scale to improve care for patients affected with rare diseases.
Plaque-associated human microglia accumulate lipid droplets in a chimeric model of Alzheimer’s disease
Authors: Claes Christel , Danhash Emma Pascal , Hasselmann Jonathan , Chadarevian Jean Paul , Shabestari Sepideh Kiani , England Whitney E. , Lim Tau En , Hidalgo Jorge Luis Silva , Spitale Robert C. , Davtyan Hayk , Blurton-Jones Mathew
Published: July 2021

Background

Disease-associated microglia (DAMs), that surround beta-amyloid plaques, represent a transcriptionally-distinct microglial profile in Alzheimer’s disease (AD). Activation of DAMs is dependent on triggering receptor expressed on myeloid cells 2 (TREM2) in mouse models and the AD TREM2-R47H risk variant reduces microglial activation and plaque association in human carriers. Interestingly, TREM2 has also been identified as a microglial lipid-sensor, and recent data indicates lipid droplet accumulation in aged microglia, that is in turn associated with a dysfunctional proinflammatory phenotype. However, whether lipid droplets (LDs) are present in human microglia in AD and how the R47H mutation affects this remains unknown.

Methods

To determine the impact of the TREM2 R47H mutation on human microglial function in vivo, we transplanted wild-type and isogenic TREM2-R47H iPSC-derived microglial progenitors into our recently developed chimeric Alzheimer mouse model. At 7 months of age scRNA-seq and histological analyses were performed.

Results

Here we report that the transcriptome of human wild-type TREM2 and isogenic TREM2-R47H DAM xenografted microglia (xMGs), isolated from chimeric AD mice, closely resembles that of human atherosclerotic foam cells. In addition, much like foam cells, plaque-bound xMGs are highly enriched in lipid droplets. Somewhat surprisingly and in contrast to a recent in vitro study, TREM2-R47H mutant xMGs exhibit an overall reduction in the accumulation of lipid droplets in vivo. Notably, TREM2-R47H xMGs also show overall reduced reactivity to plaques, including diminished plaque-proximity, reduced CD9 expression, and lower secretion of plaque-associated APOE.

Conclusions

Altogether, these results indicate lipid droplet accumulation occurs in human DAM xMGs in AD, but is reduced in TREM2-R47H DAM xMGs, as it occurs secondary to TREM2-mediated changes in plaque proximity and reactivity.
Biological knowledge-slanted random forest approach for the classification of calcified aortic valve stenosis
Authors: Cantor Erika , Salas Rodrigo , Rosas Harvey , Guauque-Olarte Sandra
Published: July 2021

Background

Calcific aortic valve stenosis (CAVS) is a fatal disease and there is no pharmacological treatment to prevent the progression of CAVS. This study aims to identify genes potentially implicated with CAVS in patients with congenital bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV) in comparison with patients having normal valves, using a knowledge-slanted random forest (RF).

Results

This study implemented a knowledge-slanted random forest (RF) using information extracted from a protein-protein interactions network to rank genes in order to modify their selection probability to draw the candidate split-variables. A total of 15,191 genes were assessed in 19 valves with CAVS (BAV, n = 10; TAV, n = 9) and 8 normal valves. The performance of the model was evaluated using accuracy, sensitivity, and specificity to discriminate cases with CAVS. A comparison with conventional RF was also performed. The performance of this proposed approach reported improved accuracy in comparison with conventional RF to classify cases separately with BAV and TAV (Slanted RF: 59.3% versus 40.7%). When patients with BAV and TAV were grouped against patients with normal valves, the addition of prior biological information was not relevant with an accuracy of 92.6%.

Conclusion

The knowledge-slanted RF approach reflected prior biological knowledge, leading to better precision in distinguishing between cases with BAV, TAV, and normal valves. The results of this study suggest that the integration of biological knowledge can be useful during difficult classification tasks.
One health pathogen surveillance demonstrated the dissemination of gut pathogens within the two coastal regions associated with intensive farming
Authors: Wang Qingyao , Zhang Yixiang , Yang Qian , Fu Songzhe , Qu Baocheng , Defoirdt Tom
Published: July 2021

Background

Intensive aquaculture farming has caused significant degradation of coastal wetlands and has been proposed as a reservoir for pathogenic Vibrio spp.

Results

Gut pathogens including Vibrio spp., Salmonella spp., and Klebsiella spp. were isolated from bird feces, shrimp and wetland water in two typical coastal regions of China in 2015 and 2017 and were subsequently subjected to whole-genome sequencing. Meanwhile, local patient isolates were also selected to confirm the epidemiological links. Bacterial community composition analyses of the sediments that were sampled in 2015 and 2017 were conducted by the hypervariable region 4 of the 16S rRNA gene. Together with the local clinical isolates, we observed highly related Vibrio isolates from waterbirds, wetlands and shrimp. Phylogenetic genome comparisons also demonstrated that sequence types ST3 and ST2414 Vibrio parahaemolyticus isolates obtained from aquatic animals were clonally related to patient isolates. Likewise, three Salmonella typhimurium isolates were also genomically related to one clinical strain. The results showed that farming activities significantly altered the community composition and resulted in the emergence of several pathogens, including Acinetobacter, Mycobacterium and Legionella.

Conclusions

In conclusion, our results demonstrated that intensive shrimp farming in wetlands has two devastating impacts: pathogen dissemination from aquatic animals into migratory birds and transmission of foodborne pathogens into local communities.
Identification of molecular biomarkers associated with disease progression in the testis of bulls infected with Besnoitia besnoiti
Authors: González-Barrio David , Diezma-Díaz Carlos , Gutiérrez-Expósito Daniel , Tabanera Enrique , Jiménez-Meléndez Alejandro , Pizarro Manuel , González-Huecas Marta , Ferre Ignacio , Ortega-Mora Luis M. , Álvarez-García Gema
Published: July 2021

Breeding bulls infected with Besnoitia besnoiti may develop sterility during either acute or chronic infection. The aim of this study was to investigate the molecular pathogenesis of B. besnoiti infection with prognosis value in bull sterility. Accordingly, five well-characterized groups of naturally and experimentally infected males were selected for the study based on clinical signs and lesions compatible with B. besnoiti infection, serological results and parasite detection. A broad panel of molecular markers representative of endothelial activation and fibrosis was investigated and complemented with a histopathological approach that included conventional histology and immunohistochemistry. The results indicated the predominance of an intense inflammatory infiltrate composed mainly of resident and recruited circulating macrophages and to a lesser extent of CD3+ cells in infected bulls. In addition, a few biomarkers were associated with acute, chronic or subclinical bovine besnoitiosis. The testicular parenchyma showed a higher number of differentially expressed genes in natural infections (acute and chronic infections) versus scrotal skin in experimental infections (subclinical infection). In subclinical infections, most genes were downregulated except for the CCL24 and CXCL2 genes, which were upregulated. In contrast, the acute phase was mainly characterized by the upregulation of IL-1α, IL-6 and TIMP1, whereas in the chronic phase, the upregulation of ICAM and the downregulation of MMP13, PLAT and IL-1α were the most relevant findings. Macrophages could be responsible for the highest level of gene regulation in the testicular parenchyma of severely affected and sterile bulls, and all these genes could be prognostic markers of sterility.
Non-convex proximal pair and relatively nonexpansive maps with respect to orbits
Authors: Shanjit Laishram , Rohen Yumnam
Published: July 2021

Every non-convex pair $(C, D)$
(
C
,
D
)
may not have proximal normal structure even in a Hilbert space. In this article, we use cyclic relatively nonexpansive maps with respect to orbits to show the presence of best proximity points in $C\cup D$
C
∪
D
, where $C\cup D$
C
∪
D
is a cyclic T-regular set and $(C, D)$
(
C
,
D
)
is a non-empty, non-convex proximal pair in a real Hilbert space. Moreover, we show the presence of best proximity points and fixed points for non-cyclic relatively nonexpansive maps with respect to orbits defined on $C\cup D$
C
∪
D
, where C and D are T-regular sets in a uniformly convex Banach space satisfying $T(C)\subseteq C$
T
(
C
)
⊆
C
, $T(D)\subseteq D$
T
(
D
)
⊆
D
wherein the convergence of Kranoselskii’s iteration process is also discussed.
Sex differences in adaptation to intermittent post-exercise sauna bathing in trained middle-distance runners
Authors: Kirby Nathalie V. , Lucas Samuel J. E. , Cable Thomas G. , Armstrong Oliver J. , Weaver Samuel R. , Lucas Rebekah A. I.
Published: July 2021

Background

The purpose of this study was to investigate the effect of sex on the efficacy of intermittent post-exercise sauna bathing to induce heat acclimation and improve markers of temperate exercise performance in trained athletes.

Methods

Twenty-six trained runners (16 female; mean ± SD, age 19 ± 1 years, V̇O2max F: 52.6 ± 6.9 mL⋅kg−1⋅min−1, M: 64.6 ± 2.4 mL⋅kg−1⋅min−1) performed a running heat tolerance test (30 min, 9 km⋅h−1/2% gradient, 40 °C/40%RH; HTT) and temperate (18 °C) exercise tests (maximal aerobic capacity [V̇O2max] and lactate profile) pre and post 3 weeks of normal exercise training plus 29 ± 1 min post-exercise sauna bathing (101–108 °C) 3 ± 1 times per week.

Results

Females and males exhibited similar reductions (interactions p > 0.05) in peak rectal temperature (− 0.3 °C; p < 0.001), skin temperature (− 0.9 °C; p < 0.001) and heart rate (− 9 beats·min−1; p = 0.001) during the HTT at post- vs pre-intervention. Only females exhibited an increase in active sweat glands on the forearm (measured via modified iodine technique; F: + 57%, p < 0.001; M: + 1%, p = 0.47). Conversely, only males increased forearm blood flow (measured via venous occlusion plethysmography; F: + 31%, p = 0.61; M: + 123%; p < 0.001). Females and males showed similar (interactions p > 0.05) improvements in V̇O2max (+ 5%; p = 0.02) and running speed at 4 mmol·L−1 blood lactate concentration (+ 0.4 km·h−1; p = 0.001).

Conclusions

Three weeks of post-exercise sauna bathing effectively induces heat acclimation in females and males, though possibly amid different thermoeffector adaptations. Post-exercise sauna bathing is also an effective ergogenic aid for both sexes.
Engagement with a diverse Stakeholder Advisory Council for research in dementia care
Authors: Masoud Sara S. , Glassner Ashlie A. , Patel Neela , Mendoza Mayra , James Deborah , Rivette Sheran , White Carole L.
Published: July 2021

Background

The inclusion of stakeholders throughout the research process has been gaining recognition as an approach that can improve the quality and impact of research. Stakeholder engagement for dementia care research has been identified as a national priority, though evaluation of engagement strategies and their impact has been limited. In dementia care research, stakeholders can include individuals living with dementia, family care partners, and health and social care professionals in dementia care. A Stakeholder Advisory Council (SAC) was established to identify priorities for dementia care research that are most important to stakeholders. Strategies to build capacity for research and facilitate engagement among the SAC were used to identify the research priorities. This study describes the experiences of SAC members engaged in the research process.

Methods

To evaluate stakeholder engagement, semi-structured interviews were conducted with members of the SAC to understand their experiences and perspectives on the strategies used to facilitate engagement and build capacity for research. Interviews were recorded, transcribed, and thematically analyzed using a mixed inductive and deductive approach. Findings were presented to members of the SAC to determine whether they felt their perspectives and experiences were accurately represented. Final domains and themes presented here were approved by the SAC.

Results

Interviews (N = 11) were conducted with members of the SAC representing each stakeholder group; persons living with dementia (n = 2); family care partners (n = 4), and health and social care professionals in dementia care (n = 5). Ten themes were categorized into four overarching domains: accessibility, council infrastructure, values and environment, and benefits of involvement.

Conclusions

Findings from this qualitative study are a resource for researchers seeking to collaborate with diverse stakeholder groups to represent their perspectives in research, including individuals living with dementia. The domains and themes identified here support the inclusion of diverse stakeholders in the research process, centering engagement and capacity building strategies around individuals living with dementia.
Inter-cluster voltage balancing control of a delta connected modular multilevel cascaded converter under unbalanced grid voltage
Authors: Oghorada Oghenewvogaga J. K. , Zhang Li , Han Huang , Esan Ayodele B. , Mao Mingxuan
Published: July 2021

A new inter-cluster DC capacitor voltage balancing scheme for a delta connected modular multilevel cascaded converter (MMCC)-based static synchronous compensator (STATCOM) is presented. A detailed power flow analysis of applying negative sequence current (NSC) and zero-sequence current (ZSC) injection methods in addressing the issue of inter-cluster DC voltage imbalance under unbalance grid voltage is carried out. A control scheme is proposed which integrates both inter-cluster methods using a quantification factor QF. This is used to achieve the sharing of the inter-cluster active power between the NSC and ZSC injection methods. An accurate method of determining the quantification factor is also presented. The proposed method offers better sub-module DC capacitor voltage balancing and prevents converter overcurrent. The influence of unbalanced grid voltage on the delta connected MMCC-based STATCOM rating using this integrated cluster balancing technique is investigated. The control scheme is verified with a 5 kV 1.2MVA MMCC-STATCOM using 3-level bridge sub-modules, and the results show the advantages of the proposed method over other inter-cluster methods.
A comparative study of dexmedetomidine and propofol infusion during monitored anesthesia care (MAC) in endoscopic retrograde cholangiopancreatography (ERCP): a randomized controlled trial
Authors: Srivastava Nidhi , Harjai Mamta , Kumar Suraj , Rai Sujeet , Malviya Deepak , Tripathi Manoj
Published: July 2021

Background

Endoscopic retrograde cholangio-pancreatography (ERCP) is an invasive procedure and hence is distressing for awake patients, requiring adequate level of sedation and analgesia. Recent advancements have encouraged use of monitored anesthesia care (MAC), that allows the patient to tolerate unpleasant procedures while maintaining cardio-respiratory function. The main aim is to compare the effect of dexmedetomidine and propofol on the hemodynamics during ERCP, quality of sedation, recovery profile, and any side effects. A total of 100 patients were randomized by a computer-generated random number table into two groups of 30 patients each. The group P received continuous propofol infusion at a rate of 25-75 mcg/kg/min to achieve a Ramsay sedation scale (RSS) of 3-4 before starting the procedure. Group D received dexmedetomidine at loading dose of 1 μg/kg i.v. over 10 min followed by 0.5 μg/kg/h infusion until RSS reached 3-4.

Results

The present study shows significant decrease in heart rate in group D (65.27 ± 4. 3 vs.77.27 ± 9.3) with more stable blood pressure values throughout than group P. There were episodes of transient desaturation in few patients in group P while no patient showed any signs of respiratory depression or desaturation in group D. The time to achieve Ramsay sedation score (RSS) 3-4 is significantly more in group D (11.4 ± 1.37 vs. 7.93 ± 1.32) with increased tendency to use rescue drug but shows better and early recovery.

Conclusion

Dexmedetomidine is a better substitute to propofol for patients undergoing ERCP; however, use of adjunct may be necessary to decrease the need for rescue drug.
Recent updates on the possible reasons for the low incidence and morbidity of COVID-19 cases in Africa
Authors: Tsinda Emmanuel Kagning , Mmbando Gideon Sadikiel
Published: July 2021

Background

The COVID-19 respiratory illness caused by the SARS-CoV-2 has been a major cause of morbidity and mortality worldwide since the first reported case in Wuhan, China. A year has passed since pandemic began, and the reasons for different COVID-19 burden variation across continents keep puzzling the general public.

Main body of the abstract

Since the COVID-19 pandemic started, published research articles have addressed the epidemiological risk factors, host factors, susceptibility and immunity. To ascertain possible reasons for the different rates of COVID-19 infections between Africa and other continents, we summarized the up-to-date scientific literature to identify possible arguments in this regard. Available literature suggests that demographic, epidemiological, sociological, genetic and immunological factors contribute in the COVID-19 severity and the susceptibly to SARS-CoV-2.

Short conclusion

This review summarizes existing data and discusses reasons for differential COVID-19 burden across continents. The arguments mentioned herein will be helpful to guide future experimental studies to test different hypotheses.
Three-step one-way model in terahertz biomedical detection
Authors: Peng Yan , Huang Jieli , Luo Jie , Yang Zhangfan , Wang Liping , Wu Xu , Zang Xiaofei , Yu Chen , Gu Min , Hu Qing , Zhang Xicheng , Zhu Yiming , Zhuang Songlin
Published: July 2021

Terahertz technology has broad application prospects in biomedical detection. However, the mixed characteristics of actual samples make the terahertz spectrum complex and difficult to distinguish, and there is no practical terahertz detection method for clinical medicine. Here, we propose a three-step one-way terahertz model, presenting a detailed flow analysis of terahertz technology in the biomedical detection of renal fibrosis as an example: 1) biomarker determination: screening disease biomarkers and establishing the terahertz spectrum and concentration gradient; 2) mixture interference removal: clearing the interfering signals in the mixture for the biomarker in the animal model and evaluating and retaining the effective characteristic peaks; and 3) individual difference removal: excluding individual interference differences and confirming the final effective terahertz parameters in the human sample. The root mean square error of our model is three orders of magnitude lower than that of the gold standard, with profound implications for the rapid, accurate and early detection of diseases.
Characterizing electromagnetic interference signals for unmanned aerial vehicle geophysical surveys
Authors: Walter Callum , Braun Alexander , Fotopoulos Georgia
Published: July 2021

The development of a functional unmanned aerial vehicle (UAV) mounted aeromagnetic system requires integrating a magnetometer payload onboard a UAV platform in a manner that preserves the integrity of the total magnetic field measurements. One challenge when developing these systems is accounting for the sources of in-flight magnetic and electromagnetic interference signals that are greater than the resolvability threshold of the magnetometer. Electromagnetic interference generated by the platform has the potential to be mitigated using several techniques such as magnetic shielding, filtering, or compensation and can be attenuated by strategically positioning the magnetometer at a distance from the UAV. The integration procedure and selection of a mitigation strategy can be informed by characterizing the electromagnetic interference generated by the platform. Scalogram analysis is used to characterize the high-frequency electromagnetic signals generated by multirotor UAV electromagnetic motors. A low-sensitivity (7 nT) vector, fluxgate magnetometer is used to measure the electromagnetic interference generated by two unique multirotor UAVs in a controlled laboratory setting. Results demonstrate three spectrally distinct electromagnetic signals, each with unique frequency and amplitude, generated by each UAV platform. The frequency of these electromagnetic interference signals is found to be directly proportional to the applied rotation frequency of the electromagnetic motor. The aforementioned knowledge is applied to UAV field surveys to assess the high-frequency electromagnetic interference signals experienced. This is achieved using a high sensitivity (0.01 nT), scalar optically pumped magnetometer with a 1000 Hz sampling frequency. Our results indicate that adequate sensor placement and preflight evaluation of the platform-sensor interactions provide useful mitigation strategies, which can compensate for electromagnetic interference signals generated by the UAV platform during aeromagnetic surveys.
Cyclophosphamide, Thalidomide, and Dexamethasone as Initial Therapy for Patients With Newly Diagnosed Multiple Myeloma in a Middle-Income Country: 7-Year Follow-Up
Authors: Vasquez Jule , Ruiz Rossana , Aliaga Karina , Valencia Fernando , Villena Marco , Quintana Shirley , Vidaurre Tatiana , Casanova Luis
Published: July 2021

PURPOSE

Major progress has occurred in multiple myeloma (MM) treatment in recent years, but this is not seen in low- and middle-income countries.

MATERIALS AND METHODS

We retrospectively assessed the efficacy and safety of cyclophosphamide, thalidomide, and dexamethasone (cyclophosphamide 400 mg/m2 for 5 days, thalidomide 100 mg once daily, if tolerated, and dexamethasone 40 mg once weekly; in 28-day cycles) in patients with newly diagnosed MM treated at our institution between April 2008 and December 2012. Survival outcomes were estimated by the Kaplan-Meier method.

RESULTS

Fifty-nine patients were found to meet the selection criteria. Median age was 56 years (27-78). Fifty-nine percent (n = 35) were male. International Staging System three was found in 24%. The median number of treatment cycles was 11 (range 4-12). After a median of 81-month follow-up (range 5-138 months), the overall response rate was 69.5%. The complete response and very good partial response were 5% and 32%, respectively. Median progression-free survival (PFS) was 35 months (95% CI, 18 to 41). The 3-year PFS was 47.4% (95% CI, 34.5 to 59.6) and 5-year PFS was 24.9% (95% CI, 14.4 to 36.9). The median of overall survival (OS) was 81 months (95% CI, 33 to not reached). The 3-year OS was 63.4% (95% CI, 49.2 to 74.6), and 5-year OS was 57.5% (95% CI, 43.2 to 69.4). The most common adverse event was neutropenia (grade 3 and 4, 30.5%). Out of 23 patients eligible for stem-cell transplantation, 10 (43.5%) proceeded with autologous transplantation. Treatment-related deaths occurred in four patients (6.7%).

CONCLUSION

Cyclophosphamide, thalidomide, and dexamethasone achieves good response rates with tolerable toxicity, especially in patients age 65 years or younger representing a feasible approach for patients with MM in low-income health care settings.
The discovery of human Plasmodium among domestic animals in West Sumba and Fakfak, Indonesia
Authors: Munirah Munirah , Wahyuni Sitti , Wahid Isra , Hamid Firdaus
Published: July 2021

Background: In Indonesia, malaria incidence is at a high rate despite maximum preventive efforts. Therefore, this study aims to determine the possibility of a Plasmodium reservoir among domestic animals in malaria-endemic areas.

Methods:  Animal blood was collected using EDTA tubes, then smeared and stained with Giemsa for Plasmodium microscopic identification. About 10 µl of blood was dropped on to a filter paper to capture Plasmodium DNA. Nested PCR was used for parasite molecular detection, while Plasmodium species were identified using the sequenced DNA.

Results: A total of 208 and 62 animal blood samples were collected from Gaura village, West Sumba and Fakfak village, West Papua, Indonesia respectively. In total, 32 samples from Gaura contained P. falciparum or P. vivax, while the Plasmodium percentage in buffalo, horse, goat, and dogs were 20.7%, 14.3%, 5.8%, 16.7%, respectively. P. knowlesi was not found in any of the samples, and no other species were detected in 18 pig blood samples.

Conclusion: Human Plasmodium existence among domestic animals in Indonesia partly explains the high prevalence and persistence of malaria in some endemic areas due to a reservoir host presence. Therefore, future studies need to ascertain the cause.
Strongyloides Hyper-Infection Syndrome and Ciliocytophthoria Mimicking Balantidium coli
Authors: Roy Moni , Ahmad Sharjeel , Sarwari Arif
Published: July 2021

Ciliocytophthoria is a phenomenon where degenerated cells in infections or malignancy can present as ciliated cells on microscopy and so may be confused with ciliated parasitic infection. We present an interesting case of recurrent shortness of breath, misdiagnosed as chronic obstructive pulmonary disease exacerbations leading to unnecessary exposure to antimicrobials and steroids. The case was diagnosed as Strongyloides hyper-infection syndrome. Another finding worth mentioning was that ciliated cells noted on broncho-alveolar lavage were thought to be a co-infection with Balantidium coli but were later confirmed as ciliocytophthoria.
Scaling up the GI workforce
Authors: Harrison Penny
Published: July 2021

Penny Harrison reviews the British Society of Gastroenterology workforce report 2021
Research round-up
Authors: Jack Kathryn
Published: July 2021

A brief overview of recently published articles on hepatology and liver nursing
Using evidence to support liver nursing practice
Authors: Munnelly Stacey
Published: July 2021

Stacey Munnelly summarises the role of evidence-based practice, competency frameworks and continuing professional development in specialist liver care
End-of-life experience and its toll on quality of life and spirituality: a cross-sectional study
Authors: Sousa Serlandia da Silva , Reis Andréa Dias , Neto José Osvaldo Barbosa , Garcia João Batista Santos
Published: July 2021

Background:

Breast and cervical/uterine cancer affect body parts that have symbolic meaning for women. Women with this diagnosis at the end-of-life often experience anxiety and depression that severely impacts their quality of life (QoL).

Aims:

This study aims to determine how the end-of-life experience impacts on the QoL and spirituality of women with advanced cancer.

Methods:

End-of-life patients and their caregivers were evaluated regarding religious and spiritual coping, depression and self-efficacy. Caregivers were interviewed regarding patients' QoL at the end-of-life. A spearman correlation test was used to evaluate correlation between variables.

Findings:

Several dimensions of positive religious and spiritual coping stood out for patients at the end of life. However, patients often experienced a negative revaluation of God. Patients reported experiencing low self-efficacy, depression and high levels of stress. The length of hospital stay, time spent in intensive care units and depression also correlated to the amount of worry and stress a patient experienced.

Conclusions:

The end-of-life patients had a poor quality of life, and experienced depression, but also used spiritual beliefs and religion as a means of coping with their end-of-life experience.
Converting hip and knee arthroplasty cases to same-day surgery due to COVID-19
Authors: Cherry Ahmed , Montgomery Spencer , Brillantes Jacqueline , Osborne Tasha , Khoshbin Amir , Daniels Timothy , Ward Sarah E. , Atrey Amit
Published: July 2021

Aims

In 2020, the COVID-19 pandemic meant that proceeding with elective surgery was restricted to minimize exposure on wards. In order to maintain throughput of elective cases, our hospital (St Michaels Hospital, Toronto, Canada) was forced to convert as many cases as possible to same-day procedures rather than overnight admission. In this retrospective analysis, we review the cases performed as same-day arthroplasty surgeries compared to the same period in the previous 12 months.

Methods

We conducted a retrospective analysis of patients undergoing total hip and knee arthroplasties over a three-month period between October and December in 2019, and again in 2020, in the middle of the COVID-19 pandemic. Patient demographics, number of outpatient primary arthroplasty cases, length of stay for admissions, 30-day readmission, and complications were collated.

Results

In total, 428 patient charts were reviewed for October to December of 2019 (n = 195) and 2020 (n = 233). Of those, total hip arthroplasties (THAs) comprised 60% and 58.8% for 2019 and 2020, respectively. Demographic data was comparable with no statistical difference for age, sex, contralateral joint arthroplasty, or BMI. American Society of Anesthesiologists grade I was more highly prevalent in the 2020 cohort (5.1-times increase; n = 13 vs n = 1). Degenerative disc disease and fibromyalgia were less significantly prevalent in the 2020 cohort. There was a significant increase in same day discharges for non-direct anterior approach THAs (two-times increase) and total knee arthroplasty (ten-times increase), with a reciprocal decrease in next day discharges. There were significantly fewer reported superficial wound infections in 2020 (5.6% vs 1.7%) and no significant differences in readmissions or emergency department visits (3.1% vs 3.0%).

Conclusion

The COVID-19 pandemic meant that hospitals and patients were hopeful to minimize the exposure to the wards, and minimize strain on the already taxed inpatient beds. With few positives during the COVID-19 crisis, the pandemic was the catalyst to speed up the outpatient arthroplasty programme that has resulted in our institution being more efficient, and with no increase in readmissions or early complications. Cite this article: Bone Jt Open 2021;2(7):545–551.
General method for replacing a thin lens with a thick lens with the same value of Seidel aberration coefficient of spherical aberration or coma
Authors: Mikš Antonín , Novák Pavel
Published: July 2021

The paper deals with the problem of replacing a thin lens with a thick lens having similar third-order aberration properties as the thin lens. The equations that make possible the calculation of parameters of the thick lens, which has the same value of focal length (or transverse magnification) and one of the Seidel aberration coefficients (either Seidel aberration coefficient of spherical aberration or Seidel aberration coefficient of coma) as the thin lens for given position of the entrance pupil and object, are derived. The application of the proposed method for calculation of parameters of the thick lens is shown in examples.
Modeling circulating cavity fields using the discrete linear canonical transform
Authors: Ciobanu A. A. , Brown D. D. , Veitch P. J. , Ottaway D. J.
Published: July 2021

Fabry–Perot cavities are central to many optical measurement systems. In high-precision experiments, such as aLIGO and AdVirgo, coupled cavities are often required, leading to complex optical behavior. We show, for the first time to our knowledge, that discrete linear canonical transforms (LCTs) can be used to compute circulating optical fields for cavities in which the optics have arbitrary apertures, reflectance and transmittance profiles, and shape. We compare the predictions of LCT models with those of alternative methods. To further highlight the utility of the LCT, we present a case study of point absorbers on the aLIGO mirrors and compare it with recently published results.
Strong couplings between magnetic quantum emitters and subwavelength all-dielectric resonators with whispering gallery modes
Authors: Hu Ma-Long , Yang Zhong-Jian , Du Xiao-Jing , Ma Lin , He Jun
Published: July 2021

Here we theoretically investigate the coherent interactions between the quantum emitters with magnetic dipole transitions and subwavelength all-dielectric resonators of whispering gallery modes (WGMs). We extend a semi-analytical method which can efficiently calculate the far-field spectrum of a general hybrid system. Then, a subwavelength sphere with refractive index around n = 3.5 is chosen as the dielectric resonator. Due to the high magnetic field enhancements of the WGMs of the sphere, strong couplings between magnetic quantum emitters and subwavelength WGMs can occur, where a clear Rabi splitting appears on the extinction spectrum of the hybrid system. The match between the relaxation times of the WGMs and emitters are important to efficiently achieve a strong enough coupling. The other parameters including the order of a WGM, the radius, the refractive index, the transition dipole moment and excitation intensity are also important factors that can affect the couplings. Our results pave the way for strong interactions between light and magnetic emitters mediated by subwavelength all-dielectric resonators.
Data rate enhancement of free space optical communication using pulse positioned differential phase shift keying
Authors: Shin Won-Ho , Lee Joon-Woo , Ha In-Ho , Han Sang-Kook
Published: July 2021

In this paper, a pulse positioned-differential phase shift keying technique is proposed to enhance the data rate in free space optical communication. Using the schematics of polarization rotation differential phase shift keying, multi-rate functionality can be achieved without using delay-line interferometers. Furthermore, the proposed novel modulation format—differential phase shift keying combined with pulse-position modulation—enables a high data rate owing to the use of an average power limited amplifier. By using the average power limited amplifier, the signal power is increased as the pulse position order increases, which enhances the bit-error-rate performance. The increased signal power can be converted to an enhanced data rate. We demonstrated that the data rate above 625 Mbps can be increased in every step, as the pulse position order increases in the pulse positioned-differential phase shift keying. The performance enhancement of the proposed technique is theoretically and experimentally demonstrated.
Ultra-broadband 3  dB power splitter from 1.55 to 2  µm wave band
Authors: Wang Zelu , Liu Yingjie , Wang Zi , Liu Yilin , Du Jiangbing , Song Qinghai , Xu Ke
Published: July 2021

Extending the optical communication wavelengths to 2 µm can significantly increase data capacity. Silicon photonics, which is a proven device integration technology, has made rapid progress at 2 µm recently. As a fundamental functional element in the photonic design kit, the 3 dB power splitter has been extensively studied in both the 1.55 µm and 2 µm regime. While the device is highly desirable to operate over both wave bands, the large waveguide dispersion in silicon makes it challenging. In this work, we demonstrate an ultra-broadband power splitter on silicon, which has a 0.2 dB bandwidth exceeding 520 nm from 1500 to 2020 nm according to simulations. The beam splitter is realized by a triple tapered Y-junction, and its operational bandwidth is greatly increased by subwavelength grating structure. The device has an ultra-compact footprint of only

3

µ

m

×

2

µ

m

. Due to the limitations on the setup and coupling technique, we measure the device bandwidth in 1.55 µm and 2 µm wave bands. The device insertion loss is measured to be below 0.4 dB from 1500 to 1620 nm and from 1960 to 2020 nm, respectively. According to these results, the proposed device is believed to be capable of operating over a broadband from 1.55 µm and 2 µm wavelengths.
Design Thinking als Werkzeug für Co-Kreation und Co-Design – Ein Erfahrungsbericht in 5 Thesen
Authors: Klein Hans Christian , Oschinsky Frederike Marie , Stelter Aida , Niehaves Bjoern
Published: July 2021

Die digitale Transformation stellt deutsche Städte und Gemeinden vor große Herausforderungen. Dabei ist es wichtig, dass der Mensch mit seinen Bedürfnissen im Mittelpunkt der Gestaltung der zukünftigen Lebens- und Arbeitsräume steht. Im vorliegenden praxisorientierten Artikel wird aufgezeigt, wie der innovative Design Thinking-Ansatz zur digitalen Transformation öffentlicher Verwaltungen beitragen kann. Anhand des Fallbeispiels eines kommunalen Open Government Labors in Nordrhein-Westfalen, welches den „Kurort der Zukunft“ gestalten möchte, können allgemeine Anregungen zur aktiven Teilhabe der Bürgerschaft und Stadtgesellschaft abgeleitet werden. Ferner werden spezielle Prinzipien für die Durchführung eines Ideen-Workshops diskutiert und mögliche Herausforderungen virtueller Formate beleuchtet. Der Beitrag schlussfolgert, dass der Design Thinking-Ansatz eine große Chance ist, den Wandel unserer Kommunen inklusiv, kollaborativ, agil zu gestalten und einen wertvollen Beitrag zu Stadtentwicklung zu liefern. Aufbauend auf unserem Anwendungsbeispiel wird insgesamt deutlich, wie und warum durch innovative Formate der Zusammenarbeit ein zusätzliches Potenzial der co-kreativen und co-produktiven Gestaltung der Städte und Gemeinden von morgen geschaffen werden kann. Das Gelernte kann schnell auf andere Fälle adaptiert und übertragen werden.
Predicting learning and achievement using GABA and glutamate concentrations in human development
Authors: Zacharopoulos George , Sella Francesco , Cohen Kadosh Kathrin , Hartwright Charlotte , Emir Uzay , Cohen Kadosh Roi
Published: July 2021

Previous research has highlighted the role of glutamate and gamma-aminobutyric acid (GABA) in learning and plasticity. What is currently unknown is how this knowledge translates to real-life complex cognitive abilities that emerge slowly and how the link between these neurotransmitters and human learning and plasticity is shaped by development. While some have suggested a generic role of glutamate and GABA in learning and plasticity, others have hypothesized that their involvement shapes sensitive periods during development. Here we used a cross-sectional longitudinal design with 255 individuals (spanning primary school to university) to show that glutamate and GABA in the intraparietal sulcus explain unique variance both in current and future mathematical achievement (approximately 1.5 years). Furthermore, our findings reveal a dynamic and dissociable role of GABA and glutamate in predicting learning, which is reversed during development, and therefore provide novel implications for models of learning and plasticity during childhood and adulthood.
A model explaining mRNA level fluctuations based on activity demands and RNA age
Authors: Xu Zhongneng , Asakawa Shuichi
Published: July 2021

Cellular RNA levels typically fluctuate and are influenced by different transcription rates and RNA degradation rates. However, the understanding of the fundamental relationships between RNA abundance, environmental stimuli, RNA activities, and RNA age distributions is incomplete. Furthermore, the rates of RNA degradation and transcription are difficult to measure in transcriptomic experiments in living organisms, especially in studies involving humans. A model based on activity demands and RNA age was developed to explore the mechanisms of RNA level fluctuations. Using single-cell time-series gene expression experimental data, we assessed the transcription rates, RNA degradation rates, RNA life spans, RNA demand, accumulated transcription levels, and accumulated RNA degradation levels. This model could also predict RNA levels under simulation backgrounds, such as stimuli that induce regular oscillations in RNA abundance, stable RNA levels over time that result from long-term shortage of total RNA activity or from uncontrollable transcription, and relationships between RNA/protein levels and metabolic rates. This information contributes to existing knowledge.
Estimating the net value of treating hepatitis C virus using sofosbuvir-velpatasvir in India
Authors: Bloom David E. , Khoury Alexander , Srinivasan V.
Published: July 2021

Recently developed direct-acting antiviral (DAA) treatments for hepatitis C virus (HCV) have been groundbreaking for their high efficacy across disease genotypes and lack of severe side effects. This study uses a cost-of-illness (COI) approach to estimate the net value conferred by this class of drugs using the cost and efficacy of one of these novel drug combinations, sofosbuvir and velpatasvir (SOF/VEL), recently licensed for generic manufacture in India. This study considers COI of lifetime earnings lost by patients and potential secondarily infected individuals due to disability and premature death from HCV infection. Expected net benefits of treatment are substantial for non-cirrhotic (NC) and compensated cirrhotic (CC) patients (ranging from 5,98,003 INR for NC women to 1,05,25,504 INR for CC men). Increased earnings are not sufficient to fully offset cost of treatment for decompensated cirrhotic individuals but treatment may still be justified on the basis of the intrinsic value of health improvements and other treatment benefits.
Pollution index of waterfowl farm assessment and prediction based on temporal convoluted network
Authors: Huang Jiande , Liu Shuangyin , Hassan Shahbaz Gul , Xu Longqin
Published: July 2021

Environmental quality is a major factor that directly impacts waterfowl productivity. Accurate prediction of pollution index (PI) is the key to improving environmental management and pollution control. This study applied a new neural network model called temporal convolutional network and a denoising algorithm called wavelet transform (WT) for predicting future 12-, 24-, and 48-hour PI values at a waterfowl farm in Shanwei, China. The temporal convoluted network (TCN) model performance was compared with that of recurrent architectures with the same capacity, long-short time memory neural network (LSTM), and gated recurrent unit (GRU). Denoised environmental data, including ammonia, temperature, relative humidity, carbon dioxide (CO2), and total suspended particles (TSP), were used to construct the forecasting model. The simulation results showed that the TCN model in general produced a more precise PI prediction and provided the highest prediction accuracy for all phases (MAE = 0.0842, 0.0859, and 0.1115; RMSE = 0.0154, 0.0167, and 0.0273; R2 = 0.9789, 0.9791, and 0.9635). The PI assessment prediction model based on TCN exhibited the best prediction accuracy and general performance compared with other parallel forecasting models and is a suitable and useful tool for predicting PI in waterfowl farms.