bluuebunny/crossref_metadata_2025 huggingface dataset:
Experiences and Struggles During COVID-19 Pandemic in India: A Qualitative Study of 12 Women
Authors: Mishra Anyesha , Roy Paromita
Published: December 2023

The crisis befalling women during COVID-19 in India is of seismic proportions affecting 620 million women from diverse sociocultural, religious and caste backgrounds and who are bound by deep-rooted patriarchy. The pandemic’s devastating effects are unfolding in menacing ways and affecting almost every domain of women’s’ lives to an almost irreparable extent—mental and physical health, income and livelihood, education and career, kinship and childcare, roles and status in society. The present study uses the qualitative method phenomenology, interviewing 12 Indian women on their experiences during the COVID-19 pandemic and how it has affected their lives at home and work. The accounts of these women are then explained and discussed through the lens of feminist movements and related literature of India, juxtaposing their voices with experiences surrounding women of this country during the pandemic. The findings have been subjected to phenomenological analysis which brought out issues related to women’s backbreaking domestic work, mental and physical abuse, effects of patriarchy on their lives, social isolation and poverty.
Factors Associated With Treatment Escalation for Psoriasis: An Analysis of Electronic Health Records Data
Authors: Rhoads Jamie L. W. , Malatestinic William N. , Burge Russel , Ganz Michael L. , Duffin Kristina C.
Published: December 2023

Background

Electronic health records (EHRs) offer the possibility of using data entry templates to simultaneously document routine clinical care and capture disease-specific measures as discrete data elements that can be used for health services research (HSR). The objective of this study was to determine factors associated with meaningful treatment escalation (MTE) of psoriasis as a pilot study for future real-world HSR studies.

Methods

We conducted a retrospective, observational cohort study of psoriasis patients by using data collected during routine clinical care from an EHR using EpiCare® SmartForms. The psoriasis SmartForm records psoriasis disease severity measures and descriptive findings to generate visit notes. These data were extracted and analyzed to identify factors associated with MTE, defined as changing or adding, phototherapy, systemic, or biologic therapy.

Results

473 psoriasis patients met study criteria; 239 underwent MTE between their first and third observed visits. Patients who experienced MTE had more severe disease at Visit 1—assessed by BSA, pPGA, oPGA, and a patient-reported disease severity measure--than patients who did not experience MTE. Other factors associated with MTE included use of topicals only or no active treatment at Visit 1, palmoplantar disease, and involvement of other difficult-to-treat body areas. Patients who underwent MTE experienced larger improvements in disease severity than those who did not.

Conclusions

This study highlights how data collected during routine clinical practice can be readily used for real-world retrospective HSR when disease measures are captured as discrete elements. This approach could provide a cost-effective platform to conduct real-world HSR.
Performance analysis of similar and dissimilar self-piercing riveted joints in aluminum alloys
Authors: Zhao Lun , Xiaole Huo , Abbas Zeshan , Zixin Guo , Islam Md Shafiqul
Published: December 2023

In this work, similar (2A12) and dissimilar (6061) aluminum alloy sheets are validly joined using self-piercing rivet process. A quasi-static experiment is proposed to investigate the mechanical behaviors, failures mode, and mechanism of the different joints. Moreover, a method based on deep learning algorithm is anticipated to detect the appearance defects of the SPR welded joints. The results indicated that 2A12 joints of similar sheets contained the advantageous static strength and 6061 similar sheet joints had superior anti-vibration performance conducts. The joints with 6061-2A12 sheets introduced the most decent and comprehensive mechanical properties. The main failure mode of 2A12 similar sheet joints was substrate fracture. The performance of the substrate affects the failure mode of the joint and the plasticity of the substrate is better. When the time comes, the failure mode is mostly pull-off failure. Poor plasticity of the substrate can easily lead to substrate breakage. The reason for joint pull-off and button fall-off failure is that there is large plastic deformation in the lower plate of the joint and the mechanical internal locking structure is damaged. 2A12 substrate breakage belongs to a composite fracture that combines intergranular fracture and microvoid aggregation type fracture. The area of the 6061 substrate near the edge of the sample is shear fracture and the area near the center of the sample thickness is dominated by microvoid aggregation type normal fracture. The effectiveness of the method was verified by conducting a series of experiments and the detection accuracy of the method can reach about 90%. The detection speed was as high as 50 frames per second (FPS), which can effectively solve the problem that the rivet quality was difficult to monitor.
Adult-onset idiopathic peripheral pulmonary artery stenosis
Authors: Tamura Yudai , Tamura Yuichi , Shigeta Ayako , Hosokawa Kazuya , Taniguchi Yu , Inami Takumi , Adachi Shiro , Tsujino Ichizo , Nakanishi Naohiko , Sato Kimi , Sakamoto Jiro , Tanabe Nobuhiro , Takama Noriaki , Nakamura Kazuto , Kubota Kayoko , Komura Naohiro , Kato Shigehiko , Yamashita Jun , Takei Makoto , Joho Shuji , Ishii Shunsuke , Takemura Ryo , Sugimura Koichiro , Tatsumi Koichiro
Published: December 2023

Background

Peripheral pulmonary artery stenosis (PPS) refers to stenosis of the pulmonary artery from the trunk to the peripheral arteries. Although paediatric PPS is well described, the clinical characteristics of adult-onset idiopathic PPS have not been established. Our objectives in this study were to characterise the disease profile of adult-onset PPS.

Methods

We collected data in Japanese centres. This cohort included patients who underwent pulmonary angiography (PAG) and excluded patients with chronic thromboembolic pulmonary hypertension or Takayasu arteritis. Patient backgrounds, right heart catheterisation (RHC) findings, imaging findings and treatment profiles were collected.

Results

44 patients (median (interquartile range) age 39 (29–57) years; 29 females (65.9%)) with PPS were enrolled from 20 centres. In PAG, stenosis of segmental and peripheral pulmonary arteries was observed in 41 (93.2%) and 36 patients (81.8%), respectively. 35 patients (79.5%) received medications approved for pulmonary arterial hypertension (PAH) and 22 patients (50.0%) received combination therapy. 25 patients (56.8%) underwent transcatheter pulmonary angioplasty. RHC data showed improvements in both mean pulmonary arterial pressure (44versus40 mmHg; p<0.001) and pulmonary vascular resistance (760versus514 dyn·s·cm−5; p<0.001) from baseline to final follow-up. The 3-, 5- and 10-year survival rates of patients with PPS were 97.5% (95% CI 83.5–99.6%), 89.0% (95% CI 68.9–96.4%) and 67.0% (95% CI 41.4–83.3%), respectively.

Conclusions

In this study, patients with adult-onset idiopathic PPS presented with segmental and peripheral pulmonary artery stenosis. Although patients had severe pulmonary hypertension at baseline, they showed a favourable treatment response to PAH drugs combined with transcatheter pulmonary angioplasty.
Spatial model of Dengue Hemorrhagic Fever (DHF) risk: scoping review
Authors: Pakaya Ririn , Daniel D. , Widayani Prima , Utarini Adi
Published: December 2023

Background

Creating a spatial model of dengue fever risk is challenging duet to many interrelated factors that could affect dengue. Therefore, it is crucial to understand how these critical factors interact and to create reliable predictive models that can be used to mitigate and control the spread of dengue.

Methods

This scoping review aims to provide a comprehensive overview of the important predictors, and spatial modelling tools capable of producing Dengue Haemorrhagic Fever (DHF) risk maps. We conducted a methodical exploration utilizing diverse sources, i.e., PubMed, Scopus, Science Direct, and Google Scholar. The following data were extracted from articles published between January 2011 to August 2022: country, region, administrative level, type of scale, spatial model, dengue data use, and categories of predictors. Applying the eligibility criteria, 45 out of 1,349 articles were selected.

Results

A variety of models and techniques were used to identify DHF risk areas with an arrangement of various multiple-criteria decision-making, statistical, and machine learning technique. We found that there was no pattern of predictor use associated with particular approaches. Instead, a wide range of predictors was used to create the DHF risk maps. These predictors may include climatology factors (e.g., temperature, rainfall, humidity), epidemiological factors (population, demographics, socio-economic, previous DHF cases), environmental factors (land-use, elevation), and relevant factors.

Conclusions

DHF risk spatial models are useful tools for detecting high-risk locations and driving proactive public health initiatives. Relying on geographical and environmental elements, these models ignored the impact of human behaviour and social dynamics. To improve the prediction accuracy, there is a need for a more comprehensive approach to understand DHF transmission dynamics.
Prevalence of G6PD deficiency and submicroscopic malaria parasites carriage in malaria hotspot area in Northwest, Tanzania
Authors: Manjurano Alphaxard , Lyimo Eric , Kishamawe Coleman , Omolo Justin , Mosha Jacklin , Donald Miyaye , Kazyoba Paul , Kapiga Saidi , Changalucha John
Published: December 2023

Background

The use of primaquine for mass drug administration (MDA) is being considered as a key strategy for malaria elimination. In addition to being the only drug active against the dormant and relapsing forms of Plasmodium vivax, primaquine is the sole potent drug against mature/infectious Plasmodium falciparum gametocytes. It may prevent onward transmission and help contain the spread of artemisinin resistance. However, higher dose of primaquine is associated with the risk of acute haemolytic anaemia in individuals with a deficiency in glucose-6-phosphate dehydrogenase. In many P. falciparum endemic areas there is paucity of information about the distribution of individuals at risk of primaquine-induced haemolysis at higher dose 45 mg of primaquine.

Methods

A retrospective cross-sectional study was carried out using archived samples to establish the prevalence of G6PD deficiency in a malaria hotspot area in Misungwi district, located in Mwanza region, Tanzania. Blood samples collected from individuals recruited between August and November 2010 were genotyped for G6PD deficiency and submicroscopic parasites carriage using polymerase chain reaction.

Results

A total of 263 individuals aged between 0 and 87 were recruited. The overall prevalence of the X-linked G6PD A− mutation was 83.7% (220/263) wild type, 8% (21/263) heterozygous and 8.4% (22/263) homozygous or hemizygous. Although, assessment of the enzymatic activity to assign the phenotypes according to severity and clinical manifestation as per WHO was not carried out, the overall genotype and allele frequency for the G6PD deficiency was 16.4% and 13. 2%, respectively. There was no statistically significant difference in among the different G6PD genotypes (p > 0.05). Out of 248 samples analysed for submicroscopic parasites carriage, 58.1% (144/248) were P. falciparum positive by PCR. G6PD heterozygous deficiency were associated with carriage of submicroscopic P. falciparum (p = 0.029).

Conclusions

This study showed that 16.4% of the population in this part of North-western Tanzania carry the G6PD A− mutation, within the range of 15–32% seen in other parts of Africa. G6PD gene mutation is widespread and heterogeneous across the study area where primaquine would be valuable for malaria control and elimination. The maps and population estimates presented here reflect potential risk of higher dose of primaquine being associated with the risk of acute haemolytic anaemia (AHA) in individuals with a deficiency in glucose-6-phosphate dehydrogenase and call further research on mapping of G6PD deficiency in Tanzania. Therefore, screening and education programmes for G6PD deficiency is warranted in a programme of malaria elimination using a higher primaquine dose.
Identification of the protein coding capability of coronavirus defective viral genomes by mass spectrometry
Authors: Lin Ching-Hung , Hsieh Feng-Cheng , Lai Chien-Chen , Wang Wei-Chen , Kuo Cheng-Yu , Yang Chun-Chun , Hsu Hsuan-Wei , Tam Hon-Man-Herman , Yang Cheng-Yao , Wu Hung-Yi
Published: December 2023

During coronavirus infection, in addition to the well-known coronavirus genomes and subgenomic mRNAs, an abundance of defective viral genomes (DVGs) can also be synthesized. In this study, we aimed to examine whether DVGs can encode proteins in infected cells. Nanopore direct RNA sequencing and liquid chromatography-tandem mass spectrometry (LC–MS/MS) analysis were employed. With the protein databases generated by nanopore direct RNA sequencing and the cell lysates derived from the RNA–protein pull-down assay, six DVG-encoded proteins were identified by LC–MS/MS based on the featured fusion peptides caused by recombination during DVG synthesis. The results suggest that the coronavirus DVGs have the capability to encode proteins. Consequently, future studies determining the biological function of DVG-encoded proteins may contribute to the understanding of their roles in coronavirus pathogenesis and the development of antiviral strategies.
EMMA: a new method for computing multiple sequence alignments given a constraint subset alignment
Authors: Shen Chengze , Liu Baqiao , Williams Kelly P. , Warnow Tandy
Published: December 2023

Background

Adding sequences into an existing (possibly user-provided) alignment has multiple applications, including updating a large alignment with new data, adding sequences into a constraint alignment constructed using biological knowledge, or computing alignments in the presence of sequence length heterogeneity. Although this is a natural problem, only a few tools have been developed to use this information with high fidelity.

Results

We present EMMA (Extending Multiple alignments using MAFFT--add) for the problem of adding a set of unaligned sequences into a multiple sequence alignment (i.e., a constraint alignment). EMMA builds on MAFFT--add, which is also designed to add sequences into a given constraint alignment. EMMA improves on MAFFT--add methods by using a divide-and-conquer framework to scale its most accurate version, MAFFT-linsi--add, to constraint alignments with many sequences. We show that EMMA has an accuracy advantage over other techniques for adding sequences into alignments under many realistic conditions and can scale to large datasets with high accuracy (hundreds of thousands of sequences). EMMA is available at https://github.com/c5shen/EMMA.

Conclusions

EMMA is a new tool that provides high accuracy and scalability for adding sequences into an existing alignment.
Impact of specialist ataxia centres on health service resource utilisation and costs across Europe: cross-sectional survey
Authors: Morris Stephen , Vallortigara Julie , Greenfield Julie , Hunt Barry , Hoffman Deborah , Reinhard Carola , Graessner Holm , Federico Antonio , Quoidbach Vinciane , Giunti Paola
Published: December 2023

Background

Little is known about the costs of treating ataxia and whether treatment at a specialist ataxia centre affects the cost of care. The aim of this study was to investigate whether patients who attended specialist ataxia centres in three European countries reported differences in their health care use and costs compared with patients who did not attend a specialist ataxia centre. We compared mean resource use and health service costs per patient affected by ataxia in the United Kingdom, Italy and Germany over a 12-month period. Data were obtained from a survey distributed to people with ataxia in the three countries. We compared mean resource use for each contact type and costs, stratifying patients by whether they were currently attending a specialist ataxia centre or had never attended one.

Results

Responses were received from 181 patients from the United Kingdom, 96 from Italy and 43 from Germany. Differences in the numbers of contacts for most types of health service use between the specialist ataxia centre and non-specialist ataxia centre groups were non-significant. In the United Kingdom the mean total cost per patient was €2209 for non-specialist ataxia centre patients and €1813 for specialist ataxia centre patients (P = 0.59). In Italy these figures were €2126 and €1971, respectively (P = 0.84). In Germany they were €2431 and €4087, respectively (P = 0.19). Inpatient stays made the largest contribution to total costs.

Conclusions

Within each country, resource use and costs were broadly similar for specialist ataxia centre and non-specialist ataxia centre groups. There were differences between countries in terms of health care contacts and costs.
∆4-3-oxo-5β-reductase deficiency: favorable outcome in 16 patients treated with cholic acid
Authors: Gardin Antoine , Ruiz Mathias , Beime Jan , Cananzi Mara , Rathert Margarete , Rohmer Barbara , Grabhorn Enke , Almes Marion , Logarajah Veena , Peña-Quintana Luis , Casswall Thomas , Darmellah-Remil Amaria , Reyes-Domínguez Ana , Barkaoui Emna , Hierro Loreto , Baquero-Montoya Carolina , Baumann Ulrich , Fischler Björn , Gonzales Emmanuel , Davit-Spraul Anne , Laplanche Sophie , Jacquemin Emmanuel
Published: December 2023

Background

Oral cholic acid therapy is an effective therapy in children with primary bile acid synthesis deficiencies. Most reported patients with this treatment have 3β-hydroxy-Δ5-C27-steroid oxidoreductase deficiency. The aim of the study was the evaluation of cholic acid therapy in a cohort of patients with the rarer Δ4-3-oxosteroid 5β-reductase (Δ4-3-oxo-R) deficiency.

Methods

Sixteen patients with Δ4-3-oxo-R deficiency confirmed by AKR1D1 gene sequencing who received oral cholic acid were retrospectively analyzed.

Results

First symptoms were reported early in life (median 2 months of age), with 14 and 3 patients having cholestatic jaundice and severe bleeding respectively. Fifteen patients received ursodeoxycholic acid before diagnosis, with partial improvement in 8 patients. Four patients had liver failure at the time of cholic acid initiation. All 16 patients received cholic acid from a median age of 8.1 months (range 3.1–159) and serum liver tests normalized in all within 6–12 months of treatment. After a median cholic acid therapy of 4.5 years (range 1.1–24), all patients were alive with their native liver. Median daily cholic acid dose at last follow-up was 8.3 mg/kg of body weight. All patients, but one, had normal physical examination and all had normal serum liver tests. Fibrosis, evaluated using liver biopsy (n = 4) or liver elastography (n = 9), had stabilized or improved. Cholic acid therapy enabled a 12-fold decrease of 3-oxo-∆4 derivatives in urine. Patients had normal growth and quality of life. The treatment was well tolerated without serious adverse events and signs of hepatotoxicity.

Conclusions

Oral cholic acid therapy is a safe and effective treatment for patients with Δ4-3-oxo-R deficiency.
Mitigating iftar-related glycemic excursions in adolescents and young adults with type 1 diabetes on MiniMed™ 780G advanced hybrid closed loop system: a randomized clinical trial for adjunctive oral vildagliptin therapy during Ramadan fasting
Authors: Elbarbary Nancy Samir , Ismail Eman Abdel Rahman
Published: December 2023

Background

Ramadan Iftar meal typically causes glucose excursions. Dipeptidyl peptidase-4 inhibitors increase glucagon-like peptide-1 and thus, decrease blood glucose levels with low risk of hypoglycemia.

Aim

To investigate the efficacy and safety of vildagliptin as an add-on therapy on glucose excursions of Iftar Ramadan meals among adolescents and young adults with type 1 diabetes mellitus (T1DM) using advanced hybrid closed-loop (AHCL) treatment.

Methods

Fifty T1DM patients on MiniMed™ 780G AHCL were randomly assigned either to receive vildagliptin (50 mg tablet) with iftar meal during Ramadan month or not. All participants received pre-meal insulin bolus based on insulin-to-carbohydrate ratio (ICR) for each meal constitution.

Results

Vildagliptin offered blunting of post-meal glucose surges (mean difference − 30.3 mg/dL [− 1.7 mmol/L] versus − 2.9 mg/dL [− 0.2 mmol/L] in control group; p < 0.001) together with concomitant exceptional euglycemia with time in range (TIR) significantly increased at end of Ramadan in intervention group from 77.8 ± 9.6% to 84.7 ± 8.3% (p = 0.016) and time above range (180–250 mg/dL) decreased from 13.6 ± 5.1% to 9.7 ± 3.6% (p = 0.003) without increasing hypoglycemia. A significant reduction was observed in automated daily correction boluses and total bolus dose by 23.9% and 16.3% (p = 0.015 and p < 0.023, respectively) with less aggressive ICR settings within intervention group at end of Ramadan. Coefficient of variation was improved from 37.0 ± 9.4% to 31.8 ± 7.1%; p = 0.035). No severe hypoglycemia or diabetic ketoacidosis were reported.

Conclusion

Adjunctive vildagliptin treatment mitigated postprandial hyperglycemia compared with pre-meal bolus alone. Vildagliptin significantly increased TIR while reducing glycemic variability without compromising safety.

Trial registration This trial was registered under ClinicalTrials.gov Identifier no. NCT06021119.
Does lower extremity alignment during normal stance predict lower limb kinematics and kinetics during drop landings?
Authors: Sayers Mark G.L. , Buhmann Robert L. , Collings Tyler J. , Mellifont Daniel B. , Stuelcken Max C.
Published: December 2023

Background

Static lower extremity alignment (LEA) during normal stance has been used clinically as a tool to determine the presence of known anterior cruciate ligament (ACL) risk factors during dynamic tasks. Previous work investigating the relationship between static LEA during normal stance and risk factors for ACL injury is limited by the use of imprecise methods or because it focuses on knee valgus only and no other potentially important variables. The aim of this investigation was to determine the relationships between static LEA and the corresponding LEA during drop landings.

Methods

Forty-one female athletes were recruited for the study (age: 19.8 ± 2.5 years, height: 1.73 ± 0.06 m, mass: 64.03 ± 6.66 kg). Lower limb kinematic data were collected using a 10 camera infrared motion capture system (500 Hz) with retro-reflective markers placed over key anatomical landmarks. This system was linked to two force platforms (1000 Hz) with subsequent three-dimensional kinematic and kinetic data developed using standard software (Visual3D). Following an appropriate warm-up, data collection involved participants standing with their arms partially abducted to record static LEA. This was following by a series of drop landings from a 0.4 m box onto the force platforms. Maximum LEA data during drop landings were then compared with static LEA.

Results

Analyses showed that in comparison to static stance, during landings the anterior tilt of the pelvis decreased while hip abduction and knee internal rotation increased. At best, static LEA variables were moderately correlated (r = -0.51 to 0.58) with peak values measured during drop landings. Additionally, regression analysis did not yield any significant predictors of any key peak hip or knee variables measured during drop landings (p = 0.15 to 0.89).

Conclusion

When combined, the poor relationships observed between kinematics during static LEA and LEA during drop landings calls into question the practice of using static measures to predict LEA during even simple landing tasks. These findings suggest static assessments of LEA may have minimal value as an ACL injury screening tool.
Impact of biochar and compost amendment on corn yield and greenhouse gas emissions under waterlogged conditions
Authors: Cho Han-Na , Shin Minji , Lee Ikhyeong , Ryoo Haeun , Acharya Bharat Sharma , Park Jae-Hyuk , Cheong Yong Hwa , Cho Ju-Sik , Kang Se-Won
Published: December 2023

Biochar, widely recognized for its capacity to counteract climate change impacts, has demonstrated substantial benefits in agricultural ecosystems. Nevertheless, empirical studies exploring its efficacy during climatic aberrations such as heavy rainfall are limited. This study investigated the effects of compost and biochar addition on corn growth attributes, yield, and soil CO2 and N2O fluxes under heavy rain (exceeding 5-yr average) and waterlogging conditions. Here, treatments included compost (CP, 7.6 t ha−1); rice husk biochar (RB, 7.6 t ha−1); wood biochar (WB, 7.6 t ha−1); and control (Cn). Under high rainfall and waterlogging, the CP treatment manifested a pronounced enhancement in corn biomass and productivity, exceeding biomass and productivity of Cn treatment by 12.6 and 32.2%, RB treatment by 120 and 195%, and WB treatment by 86.1 and 111%, respectively. Corn yield increased in the order: CP > Cn > WB > RB. Intriguingly, negligible disparity occurred between the RB and WB treatments in straw yield, grain yield, grain index, and corn productivity but both treatments recorded distinctively lower values than CP treatment. Also, the CO2 and N2O fluxes remained largely similar for two biochar treatments but lower than CP treatment. Overall, CP increased corn yield, straw, and grain yield whereas biochars reduced N2O flux during waterlogging. Although derived from a short-term experimental window, these pivotal findings furnish invaluable insights for devising soil amendments for yield and environmental benefits in contexts of extreme climatic perturbations. Our findings offer a robust foundation for refining nutrient management strategies confronted with waterlogging challenges, but long-term studies are necessary for definitive conclusions.
Dolutegravir-induced growth and lifespan effects in Caenorhabditis elegans
Authors: Kuo Shin-Huei , Hsu Wen-Li , Wu Ching-Ying , Lai Yu-Chang , Chen Tun-Chieh
Published: December 2023

Background

Integrase strand transfer inhibitor (INSTIs)-based combination antiretroviral treatment in people living with HIV (PLWH) has been reportedly correlated with several adverse effects, such as weight gain, fetal defects or psychiatric disorders.

Methods

To comprehensively understand the adverse effect of INSTIs, our study utilized Caenorhabditis Elegans (C. elegans) as a model to investigate how dolutegravir (DTG) affected its life cycle, growth, reproduction and lifespan.

Results

Our results indicated that DTG enhanced body growth at the early stage of treatment, but no change was detected for long-term treatment. The treatment also influenced the reproductive system, decreased egg-hatching but had no effect on egg-laying. Besides, DTG resulted in lifespan reduction, which is dependent on increased levels of reactive oxidative species (ROS) accumulation. Treatment with N-acetyl-cysteine (NAC) in worms restrained intracellular ROS accumulation and improved DTG-induced lifespan reduction.

Conclusions

Our study demonstrates for the first time the effect of DTG treatment on life cycle. DTG-induced adverse effects are potentially associated with intracellular ROS accumulation. Quenching ROS accumulation might provide a novel strategy for dealing with the adverse effects of INSTIs.
Algorithm for generating neutrosophic data using accept-reject method
Authors: Aslam Muhammad , Alamri Faten S.
Published: December 2023

This paper introduces a novel and innovative approach to simulating random variates from two distinct probability distributions, namely the neutrosophic uniform distribution and the neutrosophic Weibull distribution. The primary objective of this research is to present a cutting-edge methodology for generating random variates by leveraging the accept-reject simulation method, particularly in the context of managing and addressing uncertainty. In addition to introducing the simulation methodology, this work will also provide comprehensive algorithms tailored to these proposed methods. These algorithms are essential for implementing the simulation techniques and will be instrumental in their practical applications. Furthermore, this study aims to explore the relationship between the level of indeterminacy and the resulting random variates. By investigating how varying degrees of indeterminacy impact random variates, we gain valuable insights into the dynamics of these distributions under different uncertainty conditions. Preliminary results suggest that random variates exhibit a trend of decreasing as indeterminacy levels increase, shedding light on the intriguing interplay between indeterminacy and random variate generation.
The novel roles of YULINK in the migration, proliferation and glycolysis of pulmonary arterial smooth muscle cells: implications for pulmonary arterial hypertension
Authors: Wu Yi-Chia , Wang Wei-Ting , Yang Ming-Chun , Su Yu-Tsun , Yeh Jwu-Lai , Hsu Jong-Hau , Wu Jiunn-Ren
Published: December 2023

Background

Abnormal remodeling of the pulmonary vasculature, characterized by the proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs) along with dysregulated glycolysis, is a pathognomonic feature of pulmonary arterial hypertension (PAH). YULINK (MIOS, Entrez Gene: 54468), a newly identified gene, has been recently shown to possess pleiotropic physiologic functions. This study aims to determine novel roles of YULINK in the regulation of PAH-related pathogenesis, including PASMC migration, proliferation and glycolysis.

Results

Our results utilized two PAH-related cell models: PASMCs treated with platelet-derived growth factor (PDGF) and PASMCs harvested from monocrotaline (MCT)-induced PAH rats (PAH-PASMCs). YULINK modulation, either by knockdown or overexpression, was found to influence PASMC migration and proliferation in both models. Additionally, YULINK was implicated in glycolytic processes, impacting glucose uptake, glucose transporter 1 (GLUT1) expression, hexokinase II (HK-2) expression, and pyruvate production in PASMCs. Notably, YULINK and GLUT1 were observed to colocalize on PASMC membranes under PAH-related pathogenic conditions. Indeed, increased YULINK expression was also detected in the pulmonary artery of human PAH specimen. Furthermore, YULINK inhibition led to the suppression of platelet-derived growth factor receptor (PDGFR) and the phosphorylation of focal adhesion kinase (FAK), phosphoinositide 3-kinase (PI3K), and protein kinase B (AKT) in both cell models. These findings suggest that the effects of YULINK are potentially mediated through the PI3K-AKT signaling pathway.

Conclusions

Our findings indicate that YULINK appears to play a crucial role in the migration, proliferation, and glycolysis in PASMCs and therefore positioning it as a novel promising therapeutic target for PAH.
Predicting adverse outcomes in adults with a community-acquired lower respiratory tract infection: a protocol for the development and validation of two prediction models for (i) all-cause hospitalisation and mortality and (ii) cardiovascular outcomes
Authors: Rijk Merijn H. , Platteel Tamara N. , Geersing Geert-Jan , Hollander Monika , Dalmolen Bert L. G. P. , Little Paul , Rutten Frans H. , van Smeden Maarten , Venekamp Roderick P.
Published: December 2023

Background

Community-acquired lower respiratory tract infections (LRTI) are common in primary care and patients at particular risk of adverse outcomes, e.g., hospitalisation and mortality, are challenging to identify. LRTIs are also linked to an increased incidence of cardiovascular diseases (CVD) following the initial infection, whereas concurrent CVD might negatively impact overall prognosis in LRTI patients. Accurate risk prediction of adverse outcomes in LRTI patients, while considering the interplay with CVD, can aid general practitioners (GP) in the clinical decision-making process, and may allow for early detection of deterioration. This paper therefore presents the design of the development and external validation of two models for predicting individual risk of all-cause hospitalisation or mortality (model 1) and short-term incidence of CVD (model 2) in adults presenting to primary care with LRTI.

Methods

Both models will be developed using linked routine electronic health records (EHR) data from Dutch primary and secondary care, and the mortality registry. Adults aged ≥ 40 years with a GP-diagnosis of LRTI between 2016 and 2019 are eligible for inclusion. Relevant patient demographics, medical history, medication use, presenting signs and symptoms, and vital and laboratory measurements will be considered as candidate predictors. Outcomes of interest include 30-day all-cause hospitalisation or mortality (model 1) and 90-day CVD (model 2). Multivariable elastic net regression techniques will be used for model development. During the modelling process, the incremental predictive value of CVD for hospitalisation or all-cause mortality (model 1) will also be assessed. The models will be validated through internal-external cross-validation and external validation in an equivalent cohort of primary care LRTI patients.

Discussion

Implementation of currently available prediction models for primary care LRTI patients is hampered by limited assessment of model performance. While considering the role of CVD in LRTI prognosis, we aim to develop and externally validate two models that predict clinically relevant outcomes to aid GPs in clinical decision-making. Challenges that we anticipate include the possibility of low event rates and common problems related to the use of EHR data, such as candidate predictor measurement and missingness, how best to retrieve information from free text fields, and potential misclassification of outcome events.
Daily COVID-19 symptom assessment over 28 days – findings from a daily direct-to-patient registry of COVID-19 positive patients
Authors: Brinkley Emma , Knuth Kendall , Kwon Tom , Mack Christina , Leister-Tebbe Heidi , Bao Weihand , Reynolds Matthew W , Dreyer Nancy
Published: December 2023

In January 2021, 999 COVID-19 positive adults in the US enrolled in an online, direct-to-patient registry to describe daily symptom severity and progression over 28 days. The most commonly reported and persistent symptoms were fatigue, headache, decreased sense of taste, decreased sense of smell, and cough. Fast resolving symptoms included gastrointestinal symptoms (nausea, vomiting, diarrhea) and those related to fever and chills. While more than half (56%) of patients reported overall symptom improvement during the 28-day study period, 60% of patients were still reporting at least 1 COVID-19 symptom at the end of 28 days. Risk factors for experiencing symptoms for longer duration included at least one of the following: older age (> 60 years), higher BMI, lung disease, and receiving medication for hypertension. The study demonstrates the value of patient-reported data to provide important and timely insights to COVID-19 disease and symptom progression and the potential of using real-world data to inform clinical trial design and endpoints.
Diffusion-weighted imaging compared to dynamic MRI in early response assessment of locoregional therapy (by trans-arterial chemoembolization & microwave ablation) of hepatocellular carcinoma
Authors: Elboghdady Aya Ahmed , Shawky Sarah Ahmed , Zaky Mona Mahmoud
Published: December 2023

Background

Purpose of this study is to compare between dynamic contrast-enhanced and diffusion-weighted MRI imaging techniques in early response assessment of hepatocellular carcinoma (HCC) after transcatheter chemoembolization and microwave ablation.

Methods

Retrospective study was done over a period of 36 months (June 2015–June 2018). The study was conducted on 69 cases; 61 patients were males and 8 were females patients age ranged from 45 to 72 years (median 60). All patients suffered from liver cirrhosis secondary to chronic viral hepatitis. They underwent diffusion-weighted MR imaging and subtraction dynamic MR imaging techniques after trans-arterial chemoembolization (TACE) and microwave ablation (MWA). The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and overall agreement were calculated for both the dynamic and the DWI images. Apparent diffusion coefficients (ADCs) were calculated searching for a cutoff value using the receiver operating characteristic curve (ROC).

Results

Our study results revealed moderate accuracy of diffusion MRI in the diagnosis of complete ablation (no residue) less than that of dynamic and subtraction sequences with 71.43% sensitivity, 88.52% specificity, 83.3% PPV and 79.4% NPV. This is attributed to that diffusion MR study is not able to detect small enhancing tumor foci that appears clearly on dynamic and subtraction MR studies. Also, these results are attributed to false positive results on diffusion study corresponding to liquefactive necrosis with hemorrhagic component post-ablation.

Conclusions

Our study concluded that subtraction and dynamic MRI had more accuracy than diffusion compared to our follow-up results. So combined subtraction dynamic MR study and diffusion is the main technique of early evaluation of post-interventional therapy of HCC to avoid pitfalls of diffusion study.
Interobserver agreement for the Vesical Imaging-Reporting and Data System (VI-RADS) in differentiating non-muscle-invasive and muscle-invasive urinary bladder tumors
Authors: Taha Noha M. , Taha Shohenda M. , Hussein Rasha S.
Published: December 2023

Background

Bladder cancer is the most common tumor of the genitourinary tract. Transitional cell carcinoma is divided into two categories: non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). In spite of the high recurrence rate, NMIBC has good prognosis, while MIBC has poor prognosis due to local organ invasion and metastases. Mp-MRI shows better tumor detection and staging. The aim of this study is to validate VI-RADS in detecting MIBC and assessing interobserver agreement and impact of reader's experience.

Results

At cutoff value of VI-RADS score ≥ 3, the VI-RADS showed sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 96.8%,83.3%, 93.8%, 90.9%, and 93%, respectively, for reader 1, 93.5%, 91.7%, 84.6%, and 93% for reader 2, and 96.8%,83.3%, 93.8%, 90.9%, and 93% for reader 3. The interobserver agreement between individual readers was excellent among the three readers.

Conclusions

Vesical imaging-reporting and data system (VI-RADS) is a good method showing satisfactory sensitivity, specificity, and diagnostic value for detecting detrusor muscle invasion.
MVA titration by plaque assay using crystal violet staining in DF-1 cells
Authors: Navarro-Forero Santiago , Dsouza Lara , Yang Zhilong
Published: December 2023

Modified Vaccinia Ankara (MVA) is a highly promising vector for generating safe vaccine candidates against many pathogens, such as HIV-1, SARS-CoV-2, and influenza viruses. The gold standard method to titrate MVA involves visualizing MVA plaques in chicken embryo fibroblasts after immunostaining. However, this method is time-consuming and costly. In this study, we evaluated the visualization of MVA plaques formed in continuous chicken embryo fibroblasts DF-1 cells using crystal violet staining. We found that MVA titration by plaque assay using crystal violet staining in DF-1 cells yielded similar results to immunostaining, with substantially reduced time and costs. The MVA plaque assay by crystal violet staining in DF-1 cells is a reliable method with accurate results and low time and financial costs.
Liquid Biopsies for Early Response Evaluation of Radium-223 in Metastatic Prostate Cancer
Authors: de Jong Anouk C. , Isebia Khrystany T. , Ling Sui Wai , de Weerd Vanja , Van Ngoc M. , Kraan Jaco , Martens John W.M. , Mehra Niven , Hamberg Paul , Lolkema Martijn P. , de Wit Ronald , van der Veldt Astrid A.M. , Wilting Saskia M.
Published: December 2023

PURPOSE

Reliable biomarkers for response monitoring during radium-223 treatment in patients with metastatic castration-resistant prostate cancer (mCRPC) are lacking. Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA), obtained from liquid biopsies, are shown to have prognostic value in mCRPC. The aim of this study was to determine the value of CTCs and ctDNA for response evaluation of radium-223.

METHODS

In this prospective multicenter study, longitudinal blood draws and imaging were performed in 28 patients with mCRPC and predominantly bone disease, who were treated with radium-223. CTCs were counted (CELLSEARCH CTC test), while fraction of ctDNA was estimated by measuring aneuploidy of cell-free DNA (cfDNA; modified Fast Aneuploidy Screening Test-Sequencing System). CTC counts and aneuploidy score (AS) were categorized as low (<5) and high (≥5). Primary and secondary clinical end points were failure-free survival (FFS), and overall survival (OS) and development of extraosseous metastases, respectively. Additionally, CTC count and AS were related to alkaline phosphatase (ALP) and total tumor volume in bone (TTVbone) on positron emission tomography-computed tomography with 68gallium prostate-specific membrane antigen.

RESULTS

FFS was longer in patients with a low CTC count or AS either at baseline or after 12 weeks, whereas for OS, only a significant association with CTC count was observed. Liquid biopsy results correlated well with ALP and TTVbone at baseline, but not with change in both parameters after three cycles of radium-223. AS and CTC count were significantly correlated.

CONCLUSION

CTC count and AS of cfDNA at baseline and during treatment predict clinical response to radium-223 in patients with mCRPC, warranting future evaluation of their value in treatment guidance.
Bilateral Cortical-sparing Adrenalectomy for the Treatment of Bilateral Aldosterone-producing Adenomas
Authors: Nanba Kazutaka , Kaneko Hiroki , Mishina Mutsuki , Tagami Tetsuya
Published: December 2023

Aldosterone-producing adenoma (APA) is 1 of the major subtypes of primary aldosteronism (PA). Although most APA occurs unilaterally, bilateral APAs have rarely been documented. Because of its rarity, optimal management of patients with bilateral APAs has not been established. Here, we report a case of bilateral APAs that was successfully treated with simultaneous bilateral cortical-sparing surgery. A 44-year-old Japanese woman was referred to us for the evaluation of PA. She had typical clinical characteristics of PA, including hypertension, hypokalemia, and high plasma aldosterone concentration with suppressed renin. She was diagnosed as having PA based on the results of confirmatory testing. Computed tomography revealed bilateral adrenal nodules with diameters of 17 and 10 mm on the right and left adrenal gland, respectively. Adrenal venous sampling indicated excess aldosterone production from bilateral adrenal lesions. She underwent simultaneous bilateral laparoscopic partial adrenalectomy that normalized her blood pressure and serum potassium levels. Aldosterone synthase immunohistochemistry on the resected adrenal tumor tissue confirmed the diagnosis of bilateral APAs. Long-term postsurgical follow-up data suggest cure of the disease without the need for glucocorticoid replacement therapy. Bilateral cortical-sparing adrenalectomy appears to be a viable treatment option at least for selected patients with bilateral APAs.
Association Between Renal Sinus Fat and Cardiometabolic and Renin-Angiotensin System Parameters in Primary Aldosteronism
Authors: Mitsuno Ryunosuke , Kaneko Kenji , Nakamura Toshifumi , Kojima Daiki , Mizutani Yosuke , Azegami Tatsuhiko , Yamaguchi Shintaro , Yamada Yoshitake , Jinzaki Masahiro , Kinouchi Kenichiro , Yoshino Jun , Hayashi Kaori
Published: December 2023

Context

Renal sinus fat (RSF) accumulation is associated with cardiometabolic diseases, such as obesity, diabetes, hypertension, and chronic kidney disease. However, clinical implications of RSF in primary aldosteronism (PA) remain unclear.

Objective

We aimed to investigate relationships between RSF volume and key cardiometabolic and renin-angiotensin system (RAS) parameters in PA patients and clarify the differences in these relationships between unilateral and bilateral subtypes.

Methods

We analyzed data obtained from well-characterized PA patients that involved 45 unilateral (median age: 52 years; 42.2% men) and 92 bilateral patients (51 years; 42.4% men).

Results

RSF volume normalized by renal volume (RSF%) was greater in the unilateral group than in the bilateral group (P < .05). RSF% was greater in men than in women (P < .05). RSF% positively correlated with parameters related to cardiometabolic risk, including age, body mass index, visceral fat volume, creatinine, triglycerides/high-density lipoprotein cholesterol ratio, uric acid, fasting glucose, and C-reactive protein regardless of PA subtypes (all P < .05). Intriguingly, RSF% positively correlated with plasma aldosterone concentration (PAC), aldosterone-to-renin ratio, and intact parathyroid hormone (iPTH) (all P < .05) in bilateral patients but did not correlate with RAS parameters and even showed an opposite trend in unilateral patients. In subgroup analyses by sex, these distinctions became more evident in women. After adjustment for potential confounders, RSF% remained positively correlated with PAC and iPTH in bilateral patients.

Conclusion

Our results indicate that RSF accumulation is involved in cardiometabolic dysfunction associated with PA. However, there were distinct correlations between RSF volume and RAS parameters according to sex and PA subtypes.