bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical efficacy of Vortioxetine and escitalopram in the treatment of depression
Authors: Shao Shichuan , Sun Baomin , Sun Huiqing
Published: April 2022

Objectives: This study was aimed to investigate the efficacy and safety of vortioxetine hydrobromide in the treatment of major depressive disorder (MDD).

Methods: One hundred and eighty patients with the newly diagnosed depression in our hospital between August 2018 and August 2019 were selected and randomly divided into an observation group and a control group, 90 each group. The control group was treated with escitalopram, and the observation group was treated with voltaxetine. The efficacy and adverse reactions were evaluated by the Hamilton Depression scale-17 (HAMD-17), Sheehan Disability Scale (SDS), Perceived Deficits Questionnaire-Depression (PDQ-D), and treatment emergent symptom scale (TESS) before treatment and at the end of the 8th and 24th week after treatment.

Results: At the end of the 8th and 24th week after treatment, the HAMD-17 scores of the two groups were lower than those before treatment (P<0.05); at the end of the 8th and 24th week after treatment, the PDQ-D and SDS scores of the two groups were lower than those before treatment (P<0.05), and the above scores of the observation group were lower than those of the control group (P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P>0.05).

Conclusion: Voltaxetine can improve cognitive function and clinical symptoms of patients with severe depression and has high safety, which is worth clinical attention.

doi: https://doi.org/10.12669/pjms.38.5.5230

How to cite this:Shao S, Sun B, Sun H. Clinical efficacy of Vortioxetine and escitalopram in the treatment of depression. Pak J Med Sci. 2022;38(5):---------. doi: https://doi.org/10.12669/pjms.38.5.5230

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Need for a single standardized licensing & residency-entrance level exam policy in the medical education system of Pakistan
Authors: Hammad Ali Syed Muhammad , Umar Masood Hafiz Muhammad , Malik Asim
Published: April 2022

doi: https://doi.org/10.12669/pjms.38.5.6464

How to cite this:Ali SMH, Masood HMU, Malik A. Need for a single standardized licensing & residency-entrance level exam policy in the medical education system of Pakistan. Pak J Med Sci. 2022;38(5):1083-1085. doi: https://doi.org/10.12669/pjms.38.5.6464

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
The complete genome sequences of Erythroxylum coca and Erythroxylum novogranatense
Authors: White Dawson M. , Meinhardt Lyndel , Bailey Bryan , Pirro Stacy
Published: April 2022

The flowering plant genus Erythroxylum contains approximately 280 species, including the economically and socially consequential crops called coca. We present the genome sequences of Erythroxylum coca and E. novogranatense, two cultigens produced for medicinal and quotidian use in the Andes and Amazon regions of South America, as well as the international cocaine industry. Sequencing was performed on an Illumina X-Ten platform, and reads were assembled by a de novo method followed by finishing via comparison with several species from the same genus. The BioProject, raw and assembled data can be accessed in GenBank for E. coca (PRJNA676123; JAJMLV000000000) and E. novogranatense (PRJNA675212; JAJKBF000000000)
Reproductive characteristics of the giant gurami sago strain (Osphronemus goramy Lacepède, 1801): basic knowledge for a future hatchery development strategy
Authors: Azrita Azrita , Syandri Hafrijal , Aryani Netti
Published: April 2022

Background: The giant gourami sago strain (Osphronemus goramy Lacepède) has been approved in 2018 as a candidate for freshwater aquaculture in Indonesia. However, information on the species’ reproduction is minimal. This study analyzed the reproductive characteristics of the gourami sago strain broodfish to provide basic knowledge for a future hatchery development strategy.

Methods: A total of 10 female and 10 male mature gourami sago strain broodfish were measured for body weight and length, and were evaluated for their reproductive characteristics.  Breeding fish were spawned naturally in a 2×1×0.6 m concrete pond with a male-female sex ratio of 1:1. Egg weight and diameter were measured in 25 eggs per female using, respectively, ACIS AD- 600i scales with 0.01 g accuracy, and a microscope (Labo model L-711) using Canon Digital Camera Software 3 . Semen was collected using plastic syringes in 3 mL aliquots, then placed in an insulated ice-cooled container, and analyzed within two hours of collection.

Results: Average weights of female and male broodfish before spawning were 2180±159.78 g and 3060±134.99 g, respectively. The relative fecundity and egg diameter were 1029±36 eggs kg-1 and 2.42±0.05 mm, respectively. The hatching rate and embryo survival to an eyed-egg stage were respectively 76.40±2.27% and 94.76±0.42%.  Sperm characteristics showed that volume was 0.60±0.12 ml kg-1 and percentage of motile sperm was 70.04±2.27%. Female broodfish weight after spawning was strongly correlated with the weight before spawned (r2 = 0.999) and absolute fecundity was also strongly correlated with female broodfish weight before spawning (r2= 0.921). Sperm concentration was moderately correlated with sperm motility (r2 = 0.556) and duration of sperm motility (r2 = 0.502).

Conclusions: The gourami sago strain broodfish has suitable reproductive characteristics for the development of hatcheries. Successful natural spawning should be followed by larval weaning and feeding technology to increase growth and survival.
Predictors of social response to COVID-19 among health care workers caring for individuals with confirmed COVID-19 in Jordan
Authors: Dalky Heyam , Khraisat Adam , Khalifeh Anas H. , Abuhammad Sawsan , Hamdan-Mansour Ayman
Published: April 2022

Background: The outbreak of COVID-19 forced public health authorities around the world to call for national emergency plans. Public responses, in the form of social discrimination and stigmatizing behaviors, are increasingly being observed against individuals with confirmed COVID-19 and healthcare workers (HCWs) caring for those individuals. Therefore, this study aimed to investigate the perception of social discrimination and coping strategies, and explore predictors of social discrimination and coping with COVID-19 among HCWs and individuals with confirmed COVID-19.

Methods: This study used a cross-sectional descriptive-comparative design to collect data, using a convenience sample of 105 individuals with confirmed COVID-19 and 109 HCWs using a web-based survey format.

Results: In this study, individuals confirmed with COVID-19 reported a high level of social discrimination compared with HCWs (t = 2.62, p < 0.01), while HCWs reported a high level of coping with COVID-19 compared to individuals with COVID-19 (t = -3.91, p < 0.001). Educational level, age, monthly income, and taking over-the-counter medication were predictors of social discrimination and coping with COVID-19 among HCWs and individuals with confirmed COVID-19.

Conclusions: The findings showed that individuals with confirmed COVID-19 were more likely to face social discrimination, and HCWs cope with COVID-19 better than ordinary individuals with confirmed COVID-19.
A pandemia da desinformação: covid-19 e as mídias sociais - do fascínio tecnológico à (auto)regulação
Authors: Wermuth Maiquel Ângelo Dezordi , Morais José Luís Bolzan de , Festugatto Adriana Martins Ferreira
Published: April 2022

ResumoO artigo analisa a utilização das novas fontes de comunicação e informação postas pela Revolução Digital no cenário de crise sanitária da Covid-19, e as práticas de autorregulação recentemente adotadas pelas plataformas intermediárias de internet, no tocante à exclusão, mediante juízo próprio, de conteúdos tidos como não informativos. Utilizou-se de pesquisa bibliográfica e documental e da abordagem hermenêutica para estabelecer uma adequada compreensão em relação à questão posta. O problema de pesquisa consiste em avaliar em que medida as mídias sociais digitais serviram de medium para o debate em torno da pandemia e como elas têm sido utilizadas para a propagação de desinformação, bem como para a aparição de um discurso antimoderno em termos de racionalidade, ciência e política. Como principais resultados, aponta-se para um possível retorno à tradição do direito social, talvez falseada, sem qualquer regulamentação pública e mecanismos de accountability.Palavras-chave: Fake news; mídias digitais; pandemia; desinformação; autorregulação AbstractThe article analyzes the use of the new sources of communication and information brought by the Digital Revolution in the scenario of the health crisis of Covid-19, and the self-regulation practices recently adopted by the intermediary internet platforms, with regard to exclusion, through their own judgment, of content considered non-informative. Bibliographic and documentary research and the hermeneutic approach were used to establish an adequate understanding in relation to the question posed. The research problem is to assess the extent to which digital social media served as a medium for the debate around the pandemic and how they have been used to spread disinformation, as well as for the appearance of an anti-modern discourse in terms of rationality, science and politics. As main results, it points to a possible return to the tradition of social law, perhaps distorted, without any public regulation and accountability mechanisms.Keywords: Fake news; digital media; pandemic; disinformation; self-regulation
Morpho-anatomical characterization and DNA barcoding of Achillea millefolium L.
Authors: ILHAM MOCHAMMAD , MUKARROMAH SITI RIZQIYATUL , RAKASHIWI GALUH AYU , INDRIATI DANI TRI , YOKU BRUNI FLARANDA , PURNAMA PUTUT RAKHMAD , JUNAIRIAH JUNAIRIAH , PRASONGSUK SEHANAT , PURNOBASUKI HERY , WAHYUNI DWI KUSUMA
Published: April 2022

Abstract. Ilham M,Mukarromah SR, Rakashiwi GA, Indriati DT, Yoku BF, Purnama PR, Junairiah, Prasongsuk S,Purnobasuki H, Wahyuni DK. 2022. Morpho-anatomical characterizationand DNA barcoding of Achillea millefolium L. Biodiversitas 23: 1958-1969. One of the important things to study the distribution of secondary metabolites in the plant body is to carry out the identification process. Morphological markers have several limitations to recognize plants, therefore supporting data is needed so that the information becomes more comprehensive. This study aims to identify Achillea millefolium L. based on morphological, anatomical, and DNA barcoding markers to obtain specific data and avoid confusion. Morphological studies were carried out descriptively using vegetative organs, while anatomical studies of rhizomes, stems, and leaves used the paraffin method. The DNA barcoding was performed by analyzinggenes from 3 different individuals. The research was carried out by amplifying and sequencing the partial gene in the ribulose-bisphosphate carboxylaselarge subunit (rbcL) regions and maturase-K (matK). The results showed that the plant had taproots, short stems due to root rosette and the leaves were double compound. The rhizome and stem tissues had almost the same structure, while the leaves had a tissue arrangement that was similar to other plants in general, except that the mesophyll tissue was undifferentiated. The results of DNA barcoding showed a percentage of identity above 98% for both the rbcLand matK genes.
Is tranexamic acid associated with decreased need for blood transfusion in percutaneous nephrolithotomy: a systematic review and meta-analysis
Authors: Prasad S , Sharma G , Devana S Kumar , Kumar S , Sharma S
Published: April 2022

Introduction

Bleeding is a common complication after percutaneous nephrolithotomy (PNL) for renal stone disease. Tranexamic acid (TXA) has been found to reduce mortality and blood transfusion in surgical and trauma patients. This review aimed to assess the safety and efficacy of TXA in patients undergoing PNL.

Methods

A systematic literature review was performed to recognise all randomised controlled trials (RCTs) comparing the use of TXA in PNL. The primary outcome of the study was to compare the need for blood transfusion with and without TXA.

Findings

Six RCTs with 1,323 patients were included in this review. Haemoglobin fall was lower in the TXA group compared with the control group, and the need for blood transfusion was reduced by 67% (odds ratio (OR) 0.33, confidence interval (CI) (0.21, 0.52), p<0.00001). However, blood loss was comparable for the two groups (mean difference −116.9, CI (−244.5,10.7) p=0.07). Length of stay and duration of surgery was significantly shorter with TXA. Furthermore, both minor and major complications were lower in the TXA group. Stone-free rate was higher with the TXA group. No thromboembolic complications were noted in the TXA group.

Conclusions

TXA is safe and efficacious for PNL with a reduction in need for blood transfusion and without an attending increase in complication rates.
Excimer laser atherectomy combined with drug-coated balloon angioplasty for the treatment of femoropopliteal arteriosclerosis obliterans
Authors: Su Z , Li Y , Yang S , Guo J , Guo, L , Gu Y
Published: April 2022

Introduction

It has been reported that excimer laser atherectomy combined with a drug-coated balloon (ELA+DCB) can achieve better results than simple balloon angioplasty, especially for the treatment of femoropopliteal in-stent restenosis. However, reports on the application of ELA+DCB in China for femoropopliteal arteriosclerosis obliterans are lacking. This study focuses on analysing the effectiveness and safety of ELA+DCB.

Methods

This was a single-centre retrospective study that enrolled patients from November 2016 to January 2019 who had femoropopliteal arteriosclerosis obliterans treated by ELA+DCB. Preoperative demographics, operative details and postoperative follow-up outcomes were analysed statistically.

Results

There were 43 patients with an average patient age of 68.0±8.6 years; 79.1% were male. In 30 cases, the lesions were de novo and the others were in-stent restenosis (ISR). During the procedure, flow-limiting dissection (48.8%) was the main adverse event and there were 17 bailout stent implantations due to dissection. Mean (±sd) ankle–brachial index (ABI) in the patients was 0.42±0.31 before the operation and 0.83±0.13 before discharge. The mean (±sd) follow-up time was 29.35±9.71 months. The primary patency rate was 66.8%, 64.3% and 60.9% at 12, 24 and 36 months. Freedom from target lesion revascularisation (TLR) was 85.7%, 80.7% and 75.3% at 12, 24 and 36 months. Rutherford categories also greatly improved during follow-up. Overall mortality was 6.9% (3/48), and no deaths were related to the intervention.

Conclusion

The use of ELA+DCB had good clinical benefit for femoropopliteal arteriosclerosis obliterans, which had good primary patency and freedom from TLR, although intraoperative complications still required attention. Multicentre randomised controlled trials with long-term follow-up are needed.
Production of Clarias gariepinus seeds through accelerated female broodstock rematuration
Authors: Hartami Prama , Mahdaliana Mahdaliana , Ayuzar Eva
Published: April 2022

This study aims to determine the effectiveness of Oodev and Turmeric flour on feed to accelerate the rematuration of female broodstock catfish for increasing seed production. Oodev hormone is believed to accelerate the maturation process of broodstock, while turmeric flour with its active ingredients can improve liver performance in the vitellogenesis process. The method was a non-factorial completely randomized design with 4 treatments and 3 replications. The treatments are Control, (A) Oodev 0.3 ml/kg of feed, (B) Turmeric flour 5 gr/kg of feed, and (C) Combination of Oodev + Turmeric flour. The results showed that C treatment was the best treatment which produced a GSI value of 14.57 ±2.53%, period of rematuration was 32.33 ±4.16 days, egg diameter was 1.27 ±0.12 mm, fecundity was 22,939.97 ±880.38 eggs/kg of broodstock weight, fertilization rate was 80.18 ±9.75%, hatching rate was 79.80 ±2.88%, and larval survival reached 83.17 ±9.69%. Meanwhile, the specific growth of seed length in all treatments had no significant effect between treatments. The results of this study will certainly provide useful information for increasing catfish seed production both in Aceh and on a Nationally. This acceleration of maturation also has a positive impact in maximizing the available broodstock without having to increase the number of catfish broodstock to produce seeds of superior quality and benefit the cultivators.Keywords:EnrichmentFemale BroodstockPerformanceRematurationReproduction
The incubation of Tinfoil barb (Barbonymus schwanenfeldii) eggs using funnel system at different temperatures
Authors: Mellisa Siska , Ramadhan Rizki Danang , Hasri Iwan , Nurfadillah Nurfadillah
Published: April 2022

Tinfoil barb (Barbonymus schwanenfeldii) is freshwater fish found in Borneo, Java, and Sumatera including in Aceh Province waters. It is known as a native species in Indonesia, locally known as Tengadak or Lampan and this species is popular for consumption due to its taste.  Tinfoil barb is targeted species of inland water for fisheries production. In recent years, the fish population has declined because of overexploitation and habitat degradation. Therefore, this study aimed to analyze the effects of temperature on Tinfoil barb (B. schwanenfeldii) eggs incubation using a funnel system. It was conducted at Balai Benih Ikan (BBI) Lukup Badak, Central Aceh Regency. The Completely Randomized Design was used as a statistical analysis method with four treatments and three replications at 22±1 oC, 25±1 oC, 28±1 oC, and 31±1 oC. Hatching was carried out using a funnel system with 100 grain/liter of eggs density for incubation. The parameters measured were hatching time and rate, egg yolk absorption time, the survival rate of the embryo, larvae abnormality, and water quality. The ANOVA test results showed that temperature significantly affected hatching time and rate, egg yolk absorption time, and larvae abnormality (P0.05). In contrast, the effect was insignificant on the survival rate of an embryo, with P0.05. It is concluded that the optimum temperatures for Tinfoil barb eggs incubation were about 25±1 oC–31±1 oC. A funnel system was more effective for incubation than the conventional system.Keywords:Tinfoil barbFishIncubationTemperatureFunnel System
Co-production and arts-informed inquiry as creative power for knowledge mobilisation
Authors: MacGregor Stephen , Cooper Amanda , Searle Michelle , Kukkonen Tiina
Published: April 2022

Background:

Interest in using arts-informed approaches within research to increase stakeholder engagement is growing; however, there is little work describing how these approaches are operationalised across contexts. This article addresses that gap by exploring the use of arts-informed approaches across three projects.

Aims and objectives:

We explore how conceptualising research and evaluation as creative endeavours, particularly in arts-informed approaches to co-production, create opportunities to move knowledge into action (knowledge mobilisation). We propose an actionable configuration of context + mechanism = outcome (CMO) to understand the influence of arts-informed approaches to co-production.

Methods:

Multi-case design and cross-case synthesis was conducted of three studies that used arts-informed approaches. A common focus across our cases was evidence use in the K-12 education sector; however, each engaged with this focus by involving different types of evidence and sets of education stakeholders.

Findings:

Arts-informed approaches and co-production were influenced by a variety of contextual factors such as relationships between researchers and stakeholders, ethical issues of collaborative research activities, approaches to meaningful stakeholder engagement, co-production of knowledge, capacity-building support and resources, and communication between multi-stakeholder partners. Outcomes included new ways of thinking about research topics based on arts-informed approaches, more positive attitudes about co-production, more relevant and useful research and evaluation findings, and increased openness to future co-productive work.

Discussion and conclusions:

Four propositions arising from this article include: (1) arts-informed approaches address context specificity and sensitivity; (2) arts-informed approaches promote engagement; (3) arts-informed approaches enhance and intertwine skills; (4) arts-informed approaches broaden thinking about impact.
Long-term effects of blue-blocking spectacle lenses on color perception
Authors: Santandreu María , Valero Eva M. , Gómez-Robledo Luis , Huertas Rafael , Martínez-Domingo Miguel-Ángel , Hernández-Andrés Javier
Published: April 2022

The use of blue-blocking filters is increasing in spectacle lens users. Despite the low absorption in the blue range, some users complain about these filters because they affect their color perception. In a pilot study we have evaluated how the long-term use of 8 different blue-blocking filters impact the color perception during more than 2 weeks on a group of 18 normal color vision observers, compared with a control group of 10 observers. The evaluation was done using the FM100, the Color Assessment and Diagnosis (CAD) and an achromatic point measurement. Our results show that there is a trend to worsen with the filters on.
Optical amplification and gain dynamics of cavity-free lasing of argon pumped by ultraviolet femtosecond pulses
Authors: Zhuang Chengxuan , Zhang Xiang , Lu Qi , Liu Yi
Published: April 2022

Argon gas excited by resonant femtosecond ultraviolet pulses gives rise to cavity-free lasing emission in the near-infrared (NIR) range. Here we reported on a pump-probe study of the optical gain of this lasing phenomenon. With the injection of an external seeding pulse, the forward signal was significantly enhanced, confirming the existence of optical gain. The temporal dynamics of the optical gain were characterized by a time-resolved measurement. It was found that the optical gain decays on a time scale of ∼ 10 ps and it does not present a significant dependence on the gas pressures. Moreover, the intensity of the forward NIR emission signal shows a linear dependence on the gas pressure. These features suggest that the nature of this forward NIR radiation is amplified spontaneous emission, not superradiance when multiple-photon resonant excitation is involved.
Pulse modulation by Bloch surface wave excitation
Authors: Asilevi Atsu L. , Pesonen Henri , Pelisset Ségoléne , Descrovi Emiliano , Roussey Matthieu , Turunen Jari
Published: April 2022

Considering dielectric multilayers with N identical bilayers and an additional terminating layer, we address the effect of Bloch surface wave excitation on the temporal characteristics of short optical pulses. When such a resonant excitation occurs within the spectrum of the incident pulse, the reflected pulse splits into leading and trailing parts, the latter having an exponentially decaying tail. The role of the number of bilayers and the level of absorption in the multilayer stack is illustrated.
Intense red emission of mixed-alkali rare-earth free germanate glass-ceramics with Mn ions
Authors: Babkina Anastasiia , Valiev Damir , Kulpina Ekaterina , Pavliuk Aleksandra , Zyryanova Ksenia , Monogarova Alina , Ignatiev Alexander , Kuzmenko Natalia , Zhizhin Evgeny , Koroleva Aleksandra
Published: April 2022

A series of germanate glasses with manganese and alkaline ions (Li, Na, K, Rb, Cs) are successfully synthesized. Only 9 out of 21 studied compositions crystallize into glass-ceramics with LiNaGe4O9 and Li2Ge7O15 nanocrystals. The glass-ceramics possess intense emission near 660-670 nm with 37% QY and two-exponential decay with lifetime equal to 1.29 msec. The fabricated materials can be used as a deep-red radiation light source for plant growth cultivation.
Neural network-based surrogate model for inverse design of metasurfaces
Authors: Jing Guoqing , Wang Peipei , Wu Haisheng , Ren Jianjun , Xie Zhiqiang , Liu Junmin , Ye Huapeng , Li Ying , Fan Dianyuan , Chen Shuqing
Published: April 2022

Metasurfaces composed of spatially arranged ultrathin subwavelength elements are promising photonic devices for manipulating optical wavefronts, with potential applications in holography, metalens, and multiplexing communications. Finding microstructures that meet light modulation requirements is always a challenge in designing metasurfaces, where parameter sweep, gradient-based inverse design, and topology optimization are the most commonly used design methods in which the massive electromagnetic iterations require the design computational cost and are sometimes prohibitive. Herein, we propose a fast inverse design method that combines a physics-based neural network surrogate model (NNSM) with an optimization algorithm. The NNSM, which can generate an accurate electromagnetic response from the geometric topologies of the meta-atoms, is constructed for electromagnetic iterations, and the optimization algorithm is used to search for the on-demand meta-atoms from the phase library established by the NNSM to realize an inverse design. This method addresses two important problems in metasurface design: fast and accurate electromagnetic wave phase prediction and inverse design through a single phase-shift value. As a proof-of-concept, we designed an orbital angular momentum (de)multiplexer based on a phase-type metasurface, and 200 Gbit/s quadrature-phase shift-keying signals were successfully transmitted with a bit error rate approaching

1.67
×

10

−
6

. Because the design is mainly based on an optimization algorithm, it can address the “one-to-many” inverse problem in other micro/nano devices such as integrated photonic circuits, waveguides, and nano-antennas.
Distinguishing excess mutations and increased cell death based on variant allele frequencies
Authors: Tibély Gergely , Schrempf Dominik , Derényi Imre , Szöllősi Gergely J.
Published: April 2022

Tumors often harbor orders of magnitude more mutations than healthy tissues. The increased number of mutations may be due to an elevated mutation rate or frequent cell death and correspondingly rapid cell turnover, or a combination of the two. It is difficult to disentangle these two mechanisms based on widely available bulk sequencing data, where sequences from individual cells are intermixed and, thus, the cell lineage tree of the tumor cannot be resolved. Here we present a method that can simultaneously estimate the cell turnover rate and the rate of mutations from bulk sequencing data. Our method works by simulating tumor growth and finding the parameters with which the observed data can be reproduced with maximum likelihood. Applying this method to a real tumor sample, we find that both the mutation rate and the frequency of death may be high.
Comparative molecular genomic analyses of a spontaneous rhesus macaque model of mismatch repair-deficient colorectal cancer
Authors: Ozirmak Lermi Nejla , Gray Stanton B. , Bowen Charles M. , Reyes-Uribe Laura , Dray Beth K. , Deng Nan , Harris R. Alan , Raveendran Muthuswamy , Benavides Fernando , Hodo Carolyn L. , Taggart Melissa W. , Colbert Maresso Karen , Sinha Krishna M. , Rogers Jeffrey , Vilar Eduardo
Published: April 2022

Colorectal cancer (CRC) remains the third most common cancer in the US with 15% of cases displaying Microsatellite Instability (MSI) secondary to Lynch Syndrome (LS) or somatic hypermethylation of the MLH1 promoter. A cohort of rhesus macaques from our institution developed spontaneous mismatch repair deficient (MMRd) CRC with a notable fraction harboring a pathogenic germline mutation in MLH1 (c.1029C<G, p.Tyr343Ter). Our study aimed to provide a detailed molecular characterization of rhesus CRC for cross-comparison with human MMRd CRC. We performed PCR-based MSI testing (n = 41), transcriptomics analysis (n = 35), reduced-representation bisulfite sequencing (RRBS) (n = 28), and MLH1 DNA methylation (n = 10) using next-generation sequencing (NGS) of rhesus CRC. Systems biology tools were used to perform gene set enrichment analysis (GSEA) for pathway discovery, consensus molecular subtyping (CMS), and somatic mutation profiling. Overall, the majority of rhesus tumors displayed high levels of MSI (MSI-H) and differential gene expression profiles that were consistent with known deregulated pathways in human CRC. DNA methylation analysis exposed differentially methylated patterns among MSI-H, MSI-L (MSI-low)/MSS (MS-stable) and LS tumors with MLH1 predominantly inactivated among sporadic MSI-H CRCs. The findings from this study support the use of rhesus macaques as an alternative animal model to mice to study carcinogenesis, develop immunotherapies and vaccines, and implement chemoprevention approaches relevant to sporadic MSI-H and LS CRC in humans.
Conserved metabolic enzymes as vaccine antigens for giardiasis
Authors: Ihara Sozaburo , Miyamoto Yukiko , Le Christine H. Y. , Tran Vivien N. , Hanson Elaine M. , Fischer Marvin , Hanevik Kurt , Eckmann Lars
Published: April 2022

Giardia lambliais a leading protozoal cause of diarrheal disease worldwide. Infection is associated with abdominal pain, malabsorption and weight loss, and protracted post-infectious syndromes. A human vaccine is not available againstG.lamblia. Prior studies with human and murine immune sera have identified several parasite antigens, including surface proteins and metabolic enzymes with intracellular functions. While surface proteins have demonstrated vaccine potential, they can exhibit significant variation betweenG.lambliastrains. By comparison, metabolic enzymes show greater conservation but their vaccine potential has not been established. To determine whether such proteins can serve as vaccine candidates, we focused on two enzymes, α-enolase (ENO) and ornithine carbamoyl transferase (OCT), which are involved in glycolysis and arginine metabolism, respectively. We show in a cohort of patients with confirmed giardiasis that both enzymes are immunogenic. Intranasal immunization with either enzyme antigen in mice induced strong systemic IgG1 and IgG2b responses and modest mucosal IgA responses, and a marked 100- to 1,000-fold reduction in peak trophozoite load upon oralG.lambliachallenge. ENO immunization also reduced the extent and duration of cyst excretion. Examination of 44 cytokines showed only minimal intestinal changes in immunized mice, although a modest increase of CCL22 was observed in ENO-immunized mice. Spectral flow cytometry revealed increased numbers and activation state of CD4 T cells in the small intestine and an increase in α4β7-expressing CD4 T cells in mesenteric lymph nodes of ENO-immunized mice. Consistent with a key role of CD4 T cells, immunization of CD4-deficient and Rag-2 deficient mice failed to induce protection, whereas mice lacking IgA were fully protected by immunization, indicating that immunity was CD4 T cell-dependent but IgA-independent. These results demonstrate that conserved metabolic enzymes can be effective vaccine antigens for protection againstG.lambliainfection, thereby expanding the repertoire of candidate antigens beyond primary surface proteins.
Reversible domain closure modulates GlnBP ligand binding affinity
Authors: Chen Qun , Li Fang , Zuo Xiaobing , Chen Jin , Qin Peiwu , Wang Chuhui , Xu Jin , Yang Danyu , Xing Baogang , Liu Ying , Jia Peng , Li Linling , Yang Chengming , Yu Dongmei
Published: April 2022

Glutamine binding protein (GlnBP) is an Escherichia Coli periplasmic binding protein, which binds and carries glutamine to the inner membrane ATP-binding cassette (ABC) transporter. GlnBP binds the ligand with affinity around 0.1μM measured by isothermal titration calorimetry (ITC) and ligand binding stabilizes protein structure shown by its increase in thermodynamic stability. However, the molecular determinant of GlnBP ligand binding is not known. Electrostatic and hydrophobic interaction between GlnBP and glutamine are critical factors. We propose that the freedome of closure movement is also vital for ligand binding. In order to approve this hypothesis, we generate a series of mutants with different linker length that has different magnitude of domain closure. Mutants show different ligand binding affinity, which indicates that the propensity of domain closure determines the ligand binding affinity. Ligand binding triggers gradual ensemble conformational change. Structural changes upon ligand binding are monitored by combination of small angle x-ray scattering (SAXS) and NMR spectroscopy. Detailed structure characterization of GlnBP contributes to a better understanding of ligand binding and provides the structural basis for biosensor design.
Intra-atrial activation pattern is useful to localize the areas of non-pulmonary vein triggers of atrial fibrillation
Authors: Sakamoto Kazuo , Mukai Yasushi , Kawai Shunsuke , Nagaoka Kazuhiro , Inoue Shujiro , Takase Susumu , Yakabe Daisuke , Ikeda Shota , Mannoji Hiroshi , Nagayama Tomomi , Chishaki Akiko , Tsutsui Hiroyuki
Published: April 2022

Background

Pulmonary vein isolation (PVI) is an established ablation procedure for atrial fibrillation (AF), however, PVI alone is insufficient to suppress AF recurrence. Non-pulmonary vein (non-PV) trigger ablation is one of the promising strategies beyond PVI and has been shown to be effective in refractory/persistent AF cases. To make non-PV trigger ablation more standardized, it is essential to develop a simple method to localize the origin of non-PV triggers.

Methods

We retrospectively analyzed 37 non-PV triggers in 751 ablation sessions for symptomatic AF from January 2017 to December 2020. Regarding non-PV triggers, intra-atrial activation interval from the earliest in right atrium (RA) to proximal coronary sinus (CS) (RA-CSp) and that from the earliest in RA to distal CS (RA-CSd) obtained by a basically-positioned duodecapolar RA-CS catheter were compared among 3 originating non-PV areas [RA, atrial septum (SEP) and left atrium (LA)].

Results

RA-CSp of RA non-PV trigger (56.4 ± 23.4 ms) was significantly longer than that of SEP non-PV (14.8 ± 25.6 ms, p = 0.019) and LA non-PV (-24.9 ± 27.9 ms, p = 0.0004). RA-CSd of RA non-PV (75.9 ± 32.1 ms) was significantly longer than that of SEP non-PV (34.2 ± 32.6 ms, p = 0.040) and LA non-PV (-13.3 ± 41.2 ms, p = 0.0008). RA-CSp and RA-CSd of SEP non-PV were significantly longer than those of LA non-PV (p = 0.022 and p = 0.016, respectively). Sensitivity and specificity of an algorithm to differentiate the area of non-PV trigger using RA-CSp (cut-off value: 50 ms) and RA-CSd (cut-off value: 0 ms) were 88% and 97% for RA non-PV, 81% and 73% for SEP non-PV, 65% and 95% for LA non-PV, respectively.

Conclusions

The analysis of intra-atrial activation sequences was useful to differentiate non-PV trigger areas. A simple algorithm to localize the area of non-PV trigger would be helpful to identify non-PV trigger sites in AF ablation.
Current status and influential factors for family health management during quarantine: A latent category analysis
Authors: Li Guangming , Li Mengying , Peng Shuzhen , Wang Ying , Ran Li , Chen Xuyu , Zhang Ling , Zhu Sirong , Chen Qi , Wang Wenjing , Xu Yang , Zhang Yubin , Tan Xiaodong
Published: April 2022

Objective

We aimed to explore factors affecting family health management during home quarantine as well as the effects of variations in family health management (FHM) on individuals’ health status.

Methods

Using stratified random sampling, 618 families in Wuhan as well as cities within its surrounding provinces were recruited and surveyed online. Latent class variables were extracted from four modules: disinfection, space layout, physical exercise, and food reserves. The analysis was conducted using the poLCA package in R software (v.4.1.0). Chi-squared tests, Fisher’s exact tests, and non-parametric Kruskal–Wallis tests were used to compare groups as appropriate.

Results

We found an overall questionnaire reliability of 0.77 and a total omega of 0.92, indicating that the survey results were credible. The Bayesian information criterion and Akaike information criterion were used to identified four latent class variables, namely latent non-family health management (18.9%) and latent low, medium, and advanced FHM (30.93%, 29.49%, and 20.59%, respectively). Gender, household income level, body mass index, the presence of a nearby community hospital, and self-rated health status showed statistically significant differences with respect to latent FHM. Moreover, we found a statistically significant difference in emotional reactions when comparing latent advanced and low to mid-level latent FHM. Compared with latent non-family health managers, we detected statistically significant differences in individual energy levels between potential family health managers at latent low and medium levels. Additionally, we found statistically significant differences in individual energy levels between latent advanced and low level family health managers.

Conclusions

We found that multiple factors, including gender, household income, and body mass index, were correlated with latent FHM during home quarantine. We conclude that FHM can meaningfully improve individuals’ health. Thus, increasing social support for individuals can improve FHM as well as individuals’ health during home quarantine.
The mTOR inhibitor Rapamycin protects from premature cellular senescence early after experimental kidney transplantation
Authors: Hoff Uwe , Markmann Denise , Thurn-Valassina Daniela , Nieminen-Kelhä Melina , Erlangga Zulrahman , Schmitz Jessica , Bräsen Jan Hinrich , Budde Klemens , Melk Anette , Hegner Björn
Published: April 2022

Interstitial fibrosis and tubular atrophy, a major cause of kidney allograft dysfunction, has been linked to premature cellular senescence. The mTOR inhibitor Rapamycin protects from senescence in experimental models, but its antiproliferative properties have raised concern early after transplantation particularly at higher doses. Its effect on senescence has not been studied in kidney transplantation, yet. Rapamycin was applied to a rat kidney transplantation model (3 mg/kg bodyweight loading dose, 1.5 mg/kg bodyweight daily dose) for 7 days. Low Rapamycin trough levels (2.1–6.8 ng/mL) prevented the accumulation of p16INK4a positive cells in tubules, interstitium, and glomerula. Expression of the cytokines MCP-1, IL-1β, and TNF-α, defining the proinflammatory senescence-associated secretory phenotype, was abrogated. Infiltration with monocytes/macrophages and CD8+ T-lymphocytes was reduced and tubular function was preserved by Rapamycin. Inhibition of mTOR was not associated with impaired structural recovery, higher glucose levels, or weight loss. mTOR inhibition with low-dose Rapamycin in the immediate posttransplant period protected from premature cellular senescence without negative effects on structural and functional recovery from preservation/reperfusion damage, glucose homeostasis, and growth in a rat kidney transplantation model. Reduced senescence might maintain the renal regenerative capacity rendering resilience to future injuries resulting in protection from interstitial fibrosis and tubular atrophy.
SARS-CoV-2 seroprevalence among healthcare workers
Authors: Wiggen Talia D. , Bohn Bruno , Ulrich Angela K. , Stovitz Steven D. , Strickland Ali J. , Naumchik Brianna M. , Walsh Sara , Smith Stephen , Baumgartner Brett , Kline Susan , Yendell Stephanie , Hedberg Craig , Beebe Timothy J. , Demmer Ryan T.
Published: April 2022

Background

Monitoring COVID-19 infection risk among health care workers (HCWs) is a public health priority. We examined the seroprevalence of SARS-CoV-2 among HCWs following the fall infection surge in Minnesota, and before and after COVID-19 vaccination. Additionally, we assessed demographic and occupational risk factors for SARS-CoV-2 infection.

Methods

We conducted two rounds of seroprevalence testing among a cohort of HCWs: samples in round 1 were collected from 11/22/20–02/21/21 and in round 2 from 12/18/20–02/15/21. Demographic and occupational exposures assessed with logistic regression were age, sex, healthcare role and setting, and number of children in the household. The primary outcome was SARS-CoV-2 IgG seropositivity. A secondary outcome, SARS-CoV-2 infection, included both seropositivity and self-reported SARS-CoV-2 test positivity.

Results

In total, 459 HCWs were tested. 43/454 (9.47%) had a seropositive sample 1 and 75/423 (17.7%) had a seropositive sample 2. By time of sample 2 collection, 54% of participants had received at least one vaccine dose and seroprevalence was 13% among unvaccinated individuals. Relative to physicians, the odds of SARS-CoV-2 infection in other roles were increased (Nurse Practitioner: OR[95%CI] 1.93[0.57,6.53], Physician’s Assistant: 1.69[0.38,7.52], Nurse: 2.33[0.94,5.78], Paramedic/EMTs: 3.86[0.78,19.0], other: 1.68[0.58,4.85]). The workplace setting was associated with SARS-CoV-2 infection (p = 0.04). SARS-CoV-2 seroprevalence among HCWs reporting duties in the ICU vs. those working in an ambulatory clinic was elevated: OR[95%CI] 2.17[1.01,4.68].

Conclusions

SARS-CoV-2 seroprevalence in HCW increased during our study period which was consistent with community infection rates. HCW role and setting—particularly working in the ICU—is associated with higher risk for SARS-CoV-2 infection.
Fangchinoline induces gallbladder cancer cell apoptosis by suppressing PI3K/Akt/XIAP axis
Authors: Li Jiandong , Cen Wenda , Tong Chenhao , Wang Luna , Zhang Weiguang , Deng Shiqing , Yu Jianhua , Lu Baochun
Published: April 2022

Gallbladder cancer (GBC) is the most common biliary tract malignancy with a dismal prognosis. The development of new drugs may help to improve prognosis. This study found that fangchinoline, a bisbenzylisoquinoline alkaloids, inhibited the proliferation and clone formation of GBC cells in a dose-dependent manner. Moreover, Hoechst staining, TUNEL assays, and flow cytometry demonstrated that fangchinoline effectively induced apoptosis in GBC cells. Further studies found that an anti-apoptotic pathway, the PI3K/Akt/XIAP axis, was significantly inhibited in GBC cells after treating with fangchinoline. Finally, we confirmed that fangchinoline restrained xenograft tumor growth in vivo. Our findings indicate that fangchinoline can be considered a potential drug for GBC treatment.
Determinants of delayed tuberculosis treatment among patients in Selangor: A study protocol
Authors: Makeswaran Punitha , Shah Shamsul Azhar , Safian Nazarudin , Muhamad Nor Asiah , Harith Abdul Aziz
Published: April 2022

The high prevalence rate and ever-increasing incidence of tuberculosis (TB) worldwide remain a significant issue in healthcare. In Malaysia, the incidence and mortality rate of TB is increasing due to the delayed presentation of TB patients to healthcare facilities. However, there is a lack of local studies on the contributing factors of delayed presentation of TB patients in Malaysia. This study aims to establish a social epidemiology framework by analysing social factors including socio-epidemiological, socio-cultural, and health-seeking behaviours associated with the delay in seeking TB treatment among patients in Selangor, Malaysia. A sequential exploratory mixed-method study design that combines qualitative and quantitative research methods will be employed. This study will recruit adult patients who have been diagnosed with TB using chest X-ray and sputum smear microscopy. Four districts with the highest recorded cases in the state of Selangor will be selected as study locations. The qualitative study will involve a Focus Group Discussion (FGD) to explore six components, namely demographic, socio-cultural, health-seeking behaviours, social support and resources, previous knowledge and experience with illness, and treatment pathway. Meanwhile, the quantitative study will incorporate a structured survey that will be developed based on the themes identified in the qualitative phase and a review of several studies in the literature. Several quality control measures will be taken while ensuring that the survey questionnaires are anonymised and participants’ confidentiality is maintained. The data obtained from both qualitative and quantitative approaches will be combined to provide a more robust assessment of the study. Given that this study will focus on districts with high recorded cases of TB in Selangor, the findings might assist to address TB-related issues such as the increasing incidence and mortality rates, which are mainly attributed to the delayed presentation of TB patients to healthcare facilities.
Polyphosphate nanoparticles enhance the fibrin stabilization by histones more efficiently than linear polyphosphates
Authors: Lovas Miklós , Tanka-Salamon Anna , Beinrohr László , Voszka István , Szabó László , Molnár Kinga , Kolev Krasimir
Published: April 2022

Introduction

Beyond the three-dimensional fibrin network, the mechanical and lytic stability of thrombi is supported by the matrix of neutrophil extracellular traps (NETs) composed of polyanionic DNA meshwork with attached proteins including polycationic histones. Polyphosphates represent another type of polyanions, which in their linear form are known to enhance the fibrin stabilizing effects of DNA and histones. However, in vivo polyphosphates are also present in the form of nanoparticles (PolyP-NP), the interference of which with the fibrin/NET matrix is poorly characterized.

Aims

To compare the effects of linear and nanoparticulate polyphosphates, and their combinations with relevant NET components (DNA, histone H3) on fibrin formation, structure, and lysis in in vitro assays focusing on histone-polyphosphate interactions.

Methods

Transmission electron microscopy and dynamic light scattering for stability of the PolyP-NP preparations. Turbidimetry for kinetics of fibrinogen clotting by thrombin and fibrin dissolution by tissue-type plasminogen activator/plasminogen. Scanning electron microscopy for fibrin structure. Surface plasmon resonance for strength of histone-PolyP interactions.

Results

Both linear PolyP and PolyP-NP accelerated the fibrin formation and slowed down its dissolution and these effects were strongly dependent on the number of individual PolyP particles and not on their size. Addition of DNA did not modify significantly the PolyP-NP effects on fibrin formation and lysis. Both linear and nanoparticulate PolyP counteracted the effect of histone in the acceleration of fibrinogen clotting by thrombin. PolyP-NP, but not linear PolyP enhanced the prolongation of lysis time in fibrin containing histone and caused more pronounced thickening of the fibrin fibers than the linear form. Finally, PolyP-NP bound weaker to histone than the linear form.

Conclusions

The interaction of PolyP with histone was a stronger modulator of fibrin formation and lysis than its interaction with DNA. In addition, the PolyP nanoparticles enhanced the thrombus stabilizing effects of histone more effectively than linear PolyP.