bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of potential risks of clinical application of Yi Dian Hong and its proprietary Chinese medicines: A review
Authors: Chen Gongzhen , Mao Leiming , Xia Huyan , Zhu Lei , Huang Jiamin , Lu Yingmin , Liu Xin , Tang Ting
Published: February 2024

Yi Dian Hong, belonging to the Asteraceae family, finds widespread use in traditional Chinese medicine for its effectiveness in clearing heat, detoxifying, promoting blood circulation, reducing swelling, and cooling the blood. Modern medical research has revealed that Yi Dian Hong and its proprietary Chinese medicines possess biological functions such as inhibiting tumor-specific angiogenesis and regulating immune-related molecules. However, studies have identified that the primary component of Yi Dian Hong contains pyrrolizidine alkaloids (PAs), a toxic substance with potential risks to the liver, lungs, genes, and a propensity for carcinogenicity. Many countries impose strict controls on the content of PAs in herbal medicines and products. Unfortunately, China currently lacks relevant content standards, thereby introducing greater clinical application risks. To ensure the safety of clinical use of Yi Dian Hong, this review will analyze the risk associated with Yi Dian Hong and its proprietary Chinese medicines in clinical applications based on the PAs content in these medicines and provide recommendations.
Adalimumab induced exacerbation of psoriasis in patients with combined pemphigus: A case report
Authors: Yao Limin , Cai Xiaoli , Du Xiaoqing , Ma Yuxin
Published: February 2024

Rationale:

Psoriasis is an immune-related disease caused by genetic factors, abnormalities in the immune system and environmental factors, while pemphigus is an autoimmune disease caused by the autoimmune system attacking the skin and mucosal tissues. Herein, we aimed to report a rare case of adalimumab induced exacerbation of psoriasis patients with pemphigus. The rare disease causes considerable challenges for clinical diagnosis and treatment.

Patient concerns:

The patient was a 43-year-old man with intermittent erythema and scaling all over the body for more than 20 years, and blisters and vesicles on the trunk and limbs for 1 month. Half a year ago, the patient had blisters on the limbs, and was diagnosed with deciduous pemphigus in a hospital, and the blisters subsided after being given traditional Chinese medicine orally. Half a month ago, the erythema area was enlarged, and adalimumab 80 mg intramuscular injection was given for 1 time after consultation in the hospital. On the following day, the area of erythema and scales was suddenly enlarged obviously compared with the previous 1, and obvious blisters and vesicles appeared on the limbs, neck, and trunk, which were aggravated progressively and accompanied by obvious itching and pain.

Diagnoses:

The patient was diagnosed with psoriasis in patients with combined pemphigus.

Intervention:

After combined treatment with methylprednisolone and cyclosporine, the skin lesions have basically recovered.

Outcomes:

The skin lesions have basically healed. Follow up for 6 months without recurrence.

Lessons:

Methylprednisolone combined with cyclosporine may be an option in treating patients with psoriasis patients with pemphigus.
Preserving the left colonic artery in radical sigmoid and rectal cancer surgery is feasible: A meta-analysis
Authors: Wang Xin , Li Jianxin , Chen Wangsheng , Yang Qingqiang
Published: February 2024

Background:

This study aims to investigate the safety and feasibility of preserving left colonic artery (LCA) in radical sigmoid and rectal cancer surgery.

Methods:

Relevant articles were systematically searched on the PubMed, Embase, and Cochrane Library. The quality of included studies was evaluated using the Cochrane Handbook. A meta-analysis was conducted to assess the surgical outcomes and oncological outcomes by RevMan 5.4 software.

Results:

Fifteen studies with a total of 5054 patients, including 2432 patients with LCA preservation and 2622 patients without LCA preservation, were included and analyzed in this study. The meta-analysis revealed that preserving LCA in radical surgery of sigmoid and rectal cancer has lower anastomotic leakage incidence (OR = 1.03, 95% confidence interval = 0.83–1.27, P < .0001). There were no significant differences in the operative time, intraoperative blood loss, number of dissected lymph nodes, postoperative complications as well as the oncological outcomes including systemic recurrence, local recurrence, 5-year overall survival rate, and 5-year disease-free survival rate.

Conclusion subsections:

This pooled analysis showed that preserving the LCA is safe and feasible in radical sigmoid and rectal cancer surgery.
Fire needle acupuncture at Neiyingxiang (EX-HN 9) in the treatment of moderate and severe refractory perennial allergic rhinitis: A case report
Authors: Ai Jianwei , Guo Suying , Wang Yaqin , Kang Yuezhi , Wang Man , Zhao Jingyi , Huang Shaoting , Wang Junge
Published: February 2024

Rationale:

In recent decades, the incidence of perennial allergic rhinitis (PAR) has been increasing annually. However, some patients could not achieve adequate symptomatic relief with routine pharmacological treatment. Consequently, there exists an urgent clinical imperative for the development of safe and efficacious treatments with sustained therapeutic impact to ameliorate the symptomatic burden and enhance the quality of life.

Patient concerns:

The patient was a 35-year-old woman. She had suffered moderate and severe refractory PAR for decades and failed to sustain symptom mitigation from regular treatment.

Diagnoses:

Perennial allergic rhinitis.

Interventions:

The patient underwent a 4-week course of fire needle acupuncture at Neiyingxiang, administered weekly, during which all allopathic medication was discontinued.

Outcomes:

The total nasal symptoms score, total non nasal symptoms score, rhinoconjunctivitis quality of life questionnaire, and the total nasal resistance of the patient were decreased after treatment and achieved symptomatic relief. Follow-up conducted 3 months post-treatment revealed enduring symptom relief, with only sporadic nasal congestion elicited by cold stimulus.

Lessons:

This case proves that, fire needle acupuncture at Neiyingxiang may be beneficial in treating moderate and severe refractory PAR patient and have a lasting effect.
Biofilm destruction activity of alpha-tocopherol against Staphylococcus aureus, Proteus mirabilis and Pseudomonas aeruginosa
Authors: Leong Pui Yee , Tan Wei Qi , Choo Wee Sim
Published: February 2024

Antibiotic resistance and the persistence of sessile cells within biofilms complicate the eradication of biofilm-related infections using conventional antibiotics. This highlights the necessity for alternate therapy methods. The objective of this study was to investigate the biofilm destruction activity of alpha-tocopherol against Staphylococcus aureus,Proteus mirabilis and Pseudomonas aeruginosa on polystyrene. Alpha-tocopherol showed significant biofilm destruction activity on the pre-formed biofilms of S. aureus (45 - 46%), P. mirabilis (42 - 54%) and P. aeruginosa (28%). Resazurin assay showed that alpha-tocopherol disrupted all bacteria biofilms without interfering with their cell viability. Scanning electron microscope images showed lower bacterial cell count and less compacted cell aggregates on polystyrene surfaces after treatment with alpha-tocopherol. This study demonstrated the biofilm destruction activity of alpha-tocopherol against S. aureus, P. mirabilis and P. aeruginosa. Alpha-tocopherol could potentially be used to decrease biofilm-associated infections of these bacteria.
Clinical and public health implications of increasing notifications of LEE-negative Shiga toxin-producing Escherichia coli in England, 2014–2022
Authors: Rodwell Ella V. , Greig David R. , Godbole Gauri , Jenkins Claire
Published: February 2024

Introduction. Shiga toxin-producing

Escherichia coli

(STEC) belong to a diverse group of gastrointestinal pathogens. The pathogenic potential of STEC is enhanced by the presence of the pathogenicity island called the Locus of Enterocyte Effacement (LEE), including the intimin encoding gene eae.

Gap statement. STEC serotypes O128:H2 (Clonal Complex [CC]25), O91:H14 (CC33), and O146:H21 (CC442) are consistently in the top five STEC serotypes isolated from patients reporting gastrointestinal symptoms in England. However, they are eae/LEE-negative and perceived to be a low risk to public health, and we know little about their microbiology and epidemiology.

Aim. We analysed clinical outcomes and genome sequencing data linked to patients infected with LEE-negative STEC belonging to CC25 (O128:H2, O21:H2), CC33 (O91:H14) and, and CC442 (O146:H21, O174:H21) in England to assess the risk to public health.

Results. There was an almost ten-fold increase between 2014 and 2022 in the detection of all STEC belonging to CC25, CC33 and CC442 (2014 n=38, 2022 n=336), and a total of 1417 cases. There was a higher proportion of female cases (55–70 %) and more adults than children, with patients aged between 20–40 and >70 most at risk across the different serotypes. Symptoms were consistent across the three dominant serotypes O91:H14 (CC33), O146:H21 (CC442) and O128:H2 (CC25) (diarrhoea >75 %; bloody diarrhoea 25–32 %; abdominal pain 64–72 %; nausea 37–45 %; vomiting 10–24 %; and fever 27–30 %). Phylogenetic analyses revealed multiple events of acquisition and loss of different stx-encoding prophage. Additional putative virulence genes were identified including iha, agn43 and subA.

Conclusions. Continued monitoring and surveillance of LEE-negative STEC infections is essential due to the increasing burden of infectious intestinal disease, and the risk that highly pathogenic strains may emerge following acquisition of the Shiga toxin subtypes associated with the most severe clinical outcomes.
Microbiota encoded fatty-acid metabolism expands tuft cells to protect tissues homeostasis duringClostridioides difficileinfection in the large intestine
Authors: Kellogg Tasia D. , Ceglia Simona , Mortzfeld Benedikt M. , Zeamer Abigail L. , Foley Sage E. , Ward Doyle V. , Bhattarai Shakti K. , McCormick Beth A. , Reboldi Andrea , Bucci Vanni
Published: February 2024

Metabolic byproducts of the intestinal microbiota are crucial in maintaining host immune tone and shaping inter-species ecological dynamics. Among these metabolites, succinate is a driver of tuft cell (TC) differentiation and consequent type 2 immunity-dependent protection against invading parasites in the small intestine. Succinate is also a growth enhancer of the nosocomial pathogenClostridioides difficilein the large intestine. To date, no research has shown the role of succinate in modulating TC dynamics in the large intestine, or the relevance of this immune pathway toC. difficilepathophysiology. Here we reveal the existence of a three-way circuit between commensal microbes,C. difficileand host epithelial cells which centers around succinate. Through selective microbiota depletion experiments we demonstrate higher levels of type 2 cytokines leading to expansion of TCs in the colon. We then demonstrate the causal role of the microbiome in modulating colonic TC abundance and subsequent type 2 cytokine induction using rational supplementation experiments with fecal transplants and microbial consortia of succinate-producing bacteria. We show that administration of a succinate-deficientBacteroides thetaiotaomicronknockout (Δfrd) significantly reduces the enhanced type 2 immunity in mono-colonized mice. Finally, we demonstrate that mice prophylactically administered with the consortium of succinate-producing bacteria show reducedC. difficile-induced morbidity and mortality compared to mice administered with heat-killed bacteria or the vehicle. This effect is reduced in a partial tuft cell knockout mouse,Pou2f3+/-, and nullified in the tuft cell knockout mouse,Pou2f3-/-, confirming that the observed protection occursviathe TC pathway. Succinate is an intermediary metabolite of the production of short-chain fatty acids, and its concentration often increases during dysbiosis. The first barrier to enteric pathogens alike is the intestinal epithelial barrier, and host maintenance and strengthening of barrier integrity is vital to homeostasis. Considering our data, we propose that activation of TC by the microbiota-produced succinate in the colon is a mechanism evolved by the host to counterbalance microbiome-derived cues that facilitate invasion by intestinal pathogens.
Behavioural responses to acute warming precede critical shifts in the cellular and physiological thermal stress responses in fish
Authors: Durhack Travis C. , Thorstensen Matt J. , Mackey Theresa E. , Aminot Mélanie , Lawrence Michael J. , Audet Céline , Enders Eva C. , Jeffries Ken M.
Published: February 2024

From a conservation perspective, it is important to identify when sub-lethal temperatures begin to adversely impact an organism. However, it is unclear whether, during acute exposures, these cellular thresholds occur at similar temperatures to other physiological or behavioural changes. To test this, we estimated temperature preference (15.1 ± 1.1 °C) using a shuttle box, thermal optima for aerobic scope (10–15 °C) using respirometry, agitation temperature (22.0 ± 1.4 °C) as the point where a fish exhibits a behavioural avoidance response and theCTmax(28.2 ± 0.4 °C) as the upper thermal limit for 1 yr old Brook Trout (Salvelinus fontinalis) acclimated to 10 °C. We then acutely exposed a different subset of fish to these temperatures and sampled tissues when they reached the target temperature or after 60 min of recovery at 10 °C. We used qPCR to estimate mRNA transcript levels of genes associated with heat shock proteins, oxidative stress, apoptosis, and inducible transcription factors. A major shift in the transcriptome response occurred near the agitation temperature, which may identify a link between the cellular stress response and the behavioural avoidance response.
LazyAF, a pipeline for accessible medium-scalein silicoprediction of protein-protein interactions
Authors: McLean Thomas C.
Published: February 2024

Artificial intelligence has revolutionized the field of protein structure prediction. However, with more powerful and complex software being developed, it is accessibility and ease of use rather than capability that is quickly becoming a limiting factor to end users. Here, I present a Google Colaboratory-based pipeline, named LazyAF, which integrates the existing ColabFold BATCH to streamline the process of medium-scale protein-protein interaction prediction. I apply LazyAF to predict the interactome of the 76 proteins encoded on a broad-host-range multi-drug resistance plasmid RK2, demonstrating the ease and accessibility the pipeline provides.

Availability

LazyAF is freely available athttps://github.com/ThomasCMcLean/LazyAF
Patient Safety of Remote Primary Care: A Qualitative Study Assessing Risks and Mitigation and Prevention Strategies
Authors: Lounsbury Olivia , Li Edmond , Lunova Tetiana , Dael Jackie van , O’Brien Niki , Alboksmaty Ahmed , Rangel-Cristales Alay , Darzi Ara , Neves Ana Luisa
Published: February 2024

Background

While virtual care delivery has numerous advantages, it can also introduce safety risks and unintended consequences. Considering that it has become an integral part of today’s healthcare service, uncovering its unintended consequences is imperative to ensure patient safety.

Objectives

This study aimed to identify patient safety risks associated with virtual primary care, as well as strategies to mitigate these risks based on the perspectives of patients and healthcare providers.

Methods

Three focus groups were conducted followed by semi-structured interviews with patients, carers and healthcare providers working in primary care. Transcripts were systematically reviewed, and thematic analysis was performed by two independent researchers.

Results

A total of 42 participants took part in the study. Three main areas for patient safety risks associated with virtual primary care were identified, including suboptimal clinical decision-making, negative impact on patients’ access to care, and worsening the workforce crisis. Strategies to mitigate these risks included providing information for patients, training triage personnel, making technical support available, standardising guidelines, setting up systems for feedback, improving continuity of care, communication, and safety netting.

Conclusions

Patients and providers now have a heightened awareness of the strengths and pitfalls of virtual care due to their increased familiarity with the use of virtual care technologies. Existing policies need to be updated and new ones devised to minimise risks associated with virtual care and support patient and provider workflows.

Public Interest Summary

The COVID-19 pandemic galvanized an emergent necessity to deliver care virtually in order to reduce disease transmission. However, given the urgency of the crisis, virtual care was being delivered with minimal protective measures for safety.

This study examines the lived experiences of both patients and providers around virtual care use in England. Potential risks of virtual care delivery, and strategies to mitigate these risks, are identified from both perspectives. The risks identified vary from the technological learning curve to the challenges associated with modified patient-provider communication. The potential solutions identified range from strategies to improve micro-level patient-provider interactions to larger-scale system changes to improve the continuity of care.

Support for patients and providers alike should be allocated to alleviate unnecessary burdens associated with virtual care. Ensuring patient safety necessitates seamless coordination and interoperability between virtual and in-person healthcare to maintain harmony between the two modes of healthcare delivery.
Assessing the genetic contribution of cumulative behavioral factors associated with longitudinal type 2 diabetes risk highlights adiposity and the brain-metabolic axis
Authors: Carvalho Nuno R. G. , He Yixuan , Smadbeck Patrick , Flannick Jason , Mercader Josep M. , Udler Miriam , Manrai Arjun K , Moreno Jordi , Patel Chirag J.
Published: February 2024

While genetic factors, behavior, and environmental exposures form a complex web of interrelated associations in type 2 diabetes (T2D), their interaction is poorly understood. Here, using data from ∼500K participants of the UK Biobank, we identify the genetic determinants of a “polyexposure risk score” (PXS) a new risk factor that consists of an accumulation of 25 associated individual-level behaviors and environmental risk factors that predict longitudinal T2D incidence. PXS-T2D had a non-zero heritability (h2= 0.18) extensive shared genetic architecture with established clinical and biological determinants of T2D, most prominently with body mass index (genetic correlation [rg] = 0.57) and Homeostatic Model Assessment for Insulin Resistance (rg= 0.51). Genetic loci associated with PXS-T2D were enriched for expression in the brain. Biobank scale data with genetic information illuminates how complex and cumulative exposures and behaviors as a whole impact T2D risk but whose biology have been elusive in genome-wide studies of T2D.
Spatial Effects of Infiltrating T cells on Neighbouring Cancer Cells and Prognosis in Stage III CRC patients
Authors: Azimi Mohammadreza , Cho Sanghee , Bozkurt Emir , McDonough Elizabeth , Kisakol Batuhan , Matveeva Anna , Salvucci Manuela , Dussmann Heiko , McDade Simon , Firat Canan , Urganci Nil , Shia Jinru , Longley Daniel B. , Ginty Fiona , Prehn Jochen H. M.
Published: February 2024

Colorectal cancer (CRC) is one of the most frequently occurring cancers, but prognostic biomarkers identifying patients at risk of recurrence are still lacking. In this study, we aimed to investigate in more detail the spatial relationship between intratumoural T cells, cancer cells, and cancer cell hallmarks, as prognostic biomarkers in stage III colorectal cancer patients. We conducted multiplexed imaging of 56 protein markers at single cell resolution on resected fixed tissue from stage III CRC patients who received adjuvant 5-fluorouracil-based chemotherapy. Images underwent segmentation for tumour, stroma and immune cells, and cancer cell ‘state’ protein marker expression was quantified at a cellular level. We developed a Python package for estimation of spatial proximity, nearest neighbour analysis focusing on cancer cell – T cell interactions at single-cell level. In our discovery cohort (MSK), we processed 462 core samples (total number of cells: 1,669,228) from 221 adjuvant 5FU-treated stage III patients. The validation cohort (HV) consisted of 272 samples (total number of cells: 853,398) from 98 stage III CRC patients. While there were trends for an association between percentage of cytotoxic T cells (across the whole cancer core), it did not reach significance (Discovery cohort: p = 0.07, Validation cohort: p = 0.19). We next utilized our region-based nearest neighbourhood approach to determine the spatial relationships between cytotoxic T cells, helper T cells and cancer cell clusters. In the both cohorts, we found that lower distance between cytotoxic T cells, T helper cells and cancer cells was significantly associated with increased disease-free survival. An unsupervised trained model that clustered patients based on the median distance between immune cells and cancer cells, as well as protein expression profiles, successfully classified patients into low-risk and high-risk groups (Discovery cohort: p = 0.01, Validation cohort: p = 0.003).
Global genomic diversity ofPseudomonas aeruginosain bronchiectasis
Authors: Harrington N.E. , Kottara A. , Cagney K. , Shepherd M.J. , Grimsey E.M. , Fu T. , Hull R.C. , Childs D.Z. , Fothergill J.L. , Chalmers J.D. , Brockhurst M.A. , Paterson S.
Published: February 2024

Background

Pseudomonas aeruginosais the dominant pathogen causing lung infections in people with both cystic fibrosis (CF) and bronchiectasis, associated with poorer outcomes. Unlike CF, bronchiectasis has been a neglected disease. More extensive genomic studies of larger bronchiectasis patient cohorts and within patient sampling are needed to improve understanding of the evolutionary mechanisms underpinningP. aeruginosainfections to guide novel and improved treatments.

Methods

We have performed genome sequencing of 2,854P. aeruginosaisolates from 180 patients attending clinics worldwide to analyse the genomic diversity between and within patient infections.

Results

We observed high genetic diversity between infections with low incidence of highly transmissible strains. Our genomic data provide evidence for the mutational targets drivingP. aeruginosaevolution in bronchiectasis. Some functions found to gain mutations were comparable to CF, including biofilm and iron acquisition, whilst others highlighted distinct evolutionary paths in bronchiectasis such as pyocin production and resistance, and a novel efflux pump gene (PA1874). We also show a high incidence of antimicrobial resistance-associated mutations and acquired resistance genes, in particular multidrug efflux and fluoroquinolone resistance mechanisms.

Conclusions

Our findings highlight important differences betweenP. aeruginosainfections in bronchiectasis and CF and provide evidence of the relatively minor role transmissible strains play in bronchiectasis. Our study provides a 10-fold increase in the available genomic data for these infections and is a global resource to improve our knowledge and understanding, to facilitate better patient outcomes.

The largest genomic study ofPseudomonas aeruginosabronchiectasis isolates to-date, providing an unprecedented global genomic resource. We highlight important differences between bronchiectasis and cystic fibrosis, including key genes under selection.
Chemokine expression profile of an innate granuloma
Authors: Amason Megan E. , Beatty Cole J. , Harvest Carissa K. , Saban Daniel R. , Miao Edward A.
Published: February 2024

Granulomas are defined by the presence of organized layers of immune cells that include macrophages. Granulomas are often characterized as a way for the immune system to contain an infection and prevent its dissemination. We recently established a mouse infection model whereChromobacterium violaceuminduces the innate immune system to form granulomas in the liver. This response successfully eradicates the bacteria and returns the liver to homeostasis. Here, we sought to characterize the chemokines involved in directing immune cells to form the distinct layers of a granuloma. We use spatial transcriptomics to investigate the spatial and temporal expression of all CC and CXC chemokines and their receptors within this granuloma response. The expression profiles change dynamically over space and time as the granuloma matures and then resolves. To investigate the importance of monocyte-derived macrophages in this immune response, we studied the role of CCR2 duringC. violaceuminfection.Ccr2−/−mice had negligible numbers of macrophages, but large numbers of neutrophils, in theC. violaceum-infected lesions. In addition, lesions had abnormal architecture resulting in loss of bacterial containment. Without CCR2, bacteria disseminated and the mice succumbed to the infection. This indicates that macrophages are critical to form a successful innate granuloma in response toC. violaceum.

Impact statement

A successful innate granuloma requires CCR2 to organize the macrophage ring, and without CCR2, mice succumb toChromobacterium violaceuminfection.
Post natal Care services utilization and satisfaction of Women in Afar Region, Awash Fentale District, Ethiopia
Authors: Weldeyohannes Getachew , Gladys Thanyani
Published: February 2024

Back ground

The percentage of women receiving a postnatal checkup within two days of delivery is higher in urban areas than in rural areas. In Afar region it was 11.6%, which is the lowest among all regional states in Ethiopia

Aim

The aim of this study is to assess the post natal care services utilizations and satisfactions of Women in Afar Region, Awash Fentale District.

METHOD

A quantitative, descriptive, cross-sectional study design was used for this study. Data were collected using a structured questionnaire administered to 422 women aged 15 to 49 years through a stratified sampling technique. Data was entered, analyzed and interpreted using SPSS computer program. Binary logistic regression model was used to identify the factors that influence maternal health care services utilization.

Result

This study revealed that 43% of the respondents were not satisfied with the care and attention given by the health care providers and approximately 52% of the respondents were not satisfied with the cleanliness of the health facilities. Regardless of the level or degree of income, husbands’ income was statistically significant and earning less income among husbands might lead women to have less PNC services utilization. Another independent variable that showed statistical significance was watching television .Women who never watched television were 58% less likely to use PNC services compared to women who watched television every day (AOR=0.414and p-value=0.008), which is less than p=0.05.

Conclusion

husbands’ income and watching television were statistically significant and earning less income among husbands might lead women to have less PNC services utilization. Much emphasis should also be given to care, attention of mothers and the cleanliness of the healthcare facilities in Awash Fentale woreda.
Performance of Immunological Assays for Universal and Differential Diagnosis of HTLV-1/2 Infection in Candidates for Blood Donations from the Brazilian Amazon
Authors: Santos Felipe Araujo , Catão Cláudio Lucas Santos , Martins Júlia Pereira , Pessoa Uzamôr Henrique Soares , Sousa Isabelle Vasconcelos , Melo Jean Silva , Souza Gláucia Lima , Araújo Nilberto Dias , Magalhães-Gama Fábio , Abrahim Cláudia Maria de Moura , Mourão Emmily Myrella Vasconcelos , Peruhype-Magalhães Vanessa , Coelho-dos-Reis Jordana Grazziela Alves , Teixeira-Carvalho Andréa , Vallinoto Antonio Carlos Rosário , Pontes Gemilson Soares , Araújo Márcio Sobreira Silva , Martins-Filho Olindo Assis , da Costa Allyson Guimarães
Published: February 2024

The present study compares the ability of distinct immunological assays (chemiluminescence immunoassay-CLIA, western blot-WB and flow cytometry-FC-Simplex and Duplex) to detect anti-HTLV antibodies in candidates for blood donations at the Amazonas State Blood Center (Brazil) between January 2018 and December 2022. Overall, 257,942 samples from candidates for blood donations were screened using CLIA, which led to 0.15% seropositivity for HTLV (409 samples). A total of 151 candidates for blood donations were enrolled for retesting with CLIA followed by additional testing using WB and FC-Simplex and Duplex analysis. Our results demonstrated that 62% (93/151), 20% (30/151) and 17% (26/151) of the samples presented positive results with retesting using CLIA, WB and FC-Simplex analysis, respectively. Additional analysis of the CLIA, WB and FC-Simplex results revealed an overall agreement of 56% for CLIA and WB (22 co-negative; 30 co-positive samples), 48% for CLIA and FC-Simplex (21 co-negative; 24 co-positive samples) and 80% for WB and FC-Simplex (51 co-negative; 23 co-positive samples). Considering the WB as the reference standard for the diagnosis of infection with HTLV-1/2, we observed that the CLIA results of ≤3.0 RLU and >10.0 RLU in the retest can be used define a negative or positive result, respectively, and could be used as new specific cut-off values. The overall agreement between WB and FC-Duplex for accomplishing the differential diagnosis was evaluated and demonstrated 100% correspondence for the diagnosis of HTLV-1 (15/15) and HTLV-2 (7/7). Our findings demonstrate that gaps in the diagnosis of infection with HTLV-1/2 could be overcome by the simultaneous use of distinct immunological assays during retesting of candidates for blood donations.
Protein identification for stroke progression via Mendelian Randomization in Million Veteran Program and UK Biobank
Authors: Elmore Andrew , Adhikari Nimish , Hartley April E , Aparicio Hugo Javier , Posner Dan C. , Hemani Gibran , Tilling Kate , Gaunt Tom R , Wilson Peter , Casas JP , Gaziano John Michael , Smith George Davey , Paternoster Lavinia , Cho Kelly , Peloso Gina M
Published: February 2024

Background

Individuals who have experienced a stroke, or transient ischemic attack, face a heightened risk of future cardiovascular events. Identification of genetic and molecular risk factors for subsequent cardiovascular outcomes may identify effective therapeutic targets to improve prognosis after an incident stroke.

Methods

We performed genome-wide association studies (GWAS) for subsequent major adverse cardiovascular events (MACE) (Ncases=51,929, Ncntrl=39,980) and subsequent arterial ischemic stroke (AIS) Ncases=45,120, Ncntrl=46,789) after first incident stroke within the Million Veteran Program and UK Biobank. We then used genetic variants associated with proteins (pQTLs) to determine the effect of 1,463 plasma protein abundances on subsequent MACE using Mendelian randomization (MR).

Results

Two variants were significantly associated with subsequent cardiovascular events: rs76472767 (OR=0.75, 95% CI = 0.64-0.85, p= 3.69x10-08) with subsequent AIS and rs13294166 (OR=1.52, 95% CI = 1.37-1.67, p=3.77x10-08) with subsequent MACE. Using MR, we identified 2 proteins with an effect on subsequent MACE after a stroke:CCL27(effect OR= 0.77, 95% CI = 0.66-0.88, adj. p=0.05), andTNFRSF14(effect OR=1.42, 95% CI = 1.24-1.60, adj. p=0.006). These proteins are not associated with incident AIS and are implicated to have a role in inflammation.

Conclusions

We found evidence that two proteins with little effect on incident stroke appear to influence subsequent MACE after incident AIS. These associations suggest that inflammation is a contributing factor to subsequent MACE outcomes after incident AIS and highlights potential novel targets.
Preference for Scientist Occupation Among Medical and Science Students in South Korea
Authors: Bae Eun Bit
Published: February 2024

Although becoming a scientist is generally a long and arduous process, fostering scientists is considered important for national development. To determine medical and science undergraduate students’ preference of scientist, a designed preference survey was administered to 191 medical and 106 science majors, online. The chi-square test, regression, and mediation models were used. The models present significant associations between group and training programs, and between master’s program and scientist preference. Surprisingly, only 24% of the science students were interested in the PhD program compared to the 79.6% of the medical students. Less than 7% in both groups expressed interest in full-time scientist occupation. The study design and findings are newly reported. A negative public consensus of scientist occupation is identified, and master training program shows strong association with choice of scientist occupation. Due to the unstable scientists’ status, a long-term follow-up is recommended afterward program completion for more effectively fostering scientists.
SlWRKY80 recruits SlHDA1 to regulates the tomato fruit ripening and color transformation
Authors: Shang Chunyu , Chen Guo , Liu Xiaoyan , Zheng Hao , Li Guobin , Wang Jiafa , Hu Songshen , Li Zhenglun , Hu Xiaohui
Published: February 2024

Fruit ripening involves key transcription factors (TF). Despite the established importance of WRKY TFs in plant development, the involvement of WRKY and its underlying mechanism in the regulation of fruit ripening and color transformation remain unclear. Here, we discovered a phenomenon where SlWRKY80 is involved in the ripening and color transformation of tomato. Overexpression ofSlWRKY80shortened the color transition cycle of tomato fruit, whereas loss-of-function mutation inSlWRKY80delays this process. On the 7thday after the color breakdown (Break+7), the fruit color was bright red inSlWRKY80-overexpression lines. SlWRKY80 could bind to downstream promoters ofSlSGR1andSlPSY1, thereby exerting a positive regulatory effect on the expression levels ofSlSGR1andSlPSY1. This regulatory activity led to the facilitation of chlorophyll a decomposition and carotenoid synthesis during the transition of fruit color, ultimately accelerating fruit ripening and color change. TheSlWRKY80knockout lines (slwrky80cr-3 andslwrky80cr-4) showed light red. Thr (The 69thamino acid) mutated to Ser of SlWRKY80 (slwrky80cr-46), SlHDA1 was recruited as a regulatory factor to enhance the regulation of downstreamSlPSY1bySlWRKY80, and inhibited theSlSGR1expression bySlWRKY80which maybe the reason why theslwrky80cr-46 knockout lines exhibited brown color. In conclusion, SlWRKY80 regulates the expression ofSlSGR1andSlPSY1by recruiting SlHDA1, thereby regulating chlorophyll decomposition and carotenoid synthesis, and further participating in fruit maturation and related fruit color formation. This research has important guiding significance for breeding tomato germplasm with excellent commercial traits.
Structural Basis for Oxidized Glutathione Recognition by the Yeast Cadmium Factor 1
Authors: Soong Tik Hang , Hotze Clare , Khandelwal Nitesh Kumar , Tomasiak Thomas M.
Published: February 2024

Transporters from the ABCC family have an essential role in detoxifying electrophilic compounds including metals, drugs, and lipids, often through conjugation with glutathione complexes. The Yeast Cadmium Factor 1 (Ycf1) transports glutathione alone as well as glutathione conjugated to toxic heavy metals including Cd2+, Hg2+, and As3+. To understand the complicated selectivity and promiscuity of heavy metal substrate binding, we determined the cryo-EM structure of Ycf1 bound to the substrate, oxidized glutathione. We systematically tested binding determinants with cellular survival assays against cadmium to determine how the substrate site accommodates differentsized metal complexes. We identify a “flex-pocket” for substrate binding that binds glutathione complexes asymmetrically and flexes to accommodate different size complexes.

Significance Statement

The molecular mechanism by which Ycf1 transports a broad array of substrates that are essential for cellular detoxification and redox homeostasis remains unknown in the field of cellular biology. Here, guided by the novel substrate bound structure of Ycf1, we discovered a bipartite binding mechanism that accommodates substrates of varying sizes while maintaining specificity. Four crucial ionic interactions govern substrate specificity by recognizing ligands with a glutathione moiety, complemented by a sizable pocket on the adjacent side for different glutathione complexes.
Multiplexing of temporal and spatial information in the lateral entorhinal cortex
Authors: Wang Cheng , Lee Heekyung , Rao Geeta , Knierim James J.
Published: February 2024

Episodic memory involves the processing of spatial and temporal aspects of personal experiences. The lateral entorhinal cortex (LEC) plays an essential role in subserving memory. However, the specific mechanism by which LEC integrates spatial and temporal information remains elusive. Here, we recorded LEC neurons while rats performed foraging and shuttling behaviors on one-dimensional, linear or circular tracks. Unlike open-field foraging tasks, many LEC cells displayed spatial firing fields in these tasks and demonstrated selectivity for traveling directions. Furthermore, some LEC neurons displayed changes in the firing rates of their spatial rate maps during a session, a phenomenon referred to as rate remapping. Importantly, this temporal modulation was consistent across sessions, even when the spatial environment was altered. Notably, the strength of temporal modulation was found to be greater in LEC compared to other brain regions, such as the medial entorhinal cortex (MEC), CA1, and CA3. Thus, the spatial rate mapping observed in LEC neurons may serve as a coding mechanism for temporal context, allowing for flexible multiplexing of spatial and temporal information.
Sublinear Scaling in Non-Markovian Open Quantum Systems Simulations
Authors: Cygorek Moritz , Keeling Jonathan , Lovett Brendon W. , Gauger Erik M.
Published: February 2024

While several numerical techniques are available for predicting the dynamics of non-Markovian open quantum systems, most struggle with simulations for very long memory and propagation times, e.g., due to superlinear scaling with the number of time steps n. Here, we introduce a numerically exact algorithm to calculate process tensors—compact representations of environmental influences—which provides a scaling advantage over previous algorithms by leveraging self-similarity of the tensor networks that represent the environment. It is applicable to environments with Gaussian statistics, such as for spin-boson-type open quantum systems. Based on a divide-and-conquer strategy, our approach requires only O(n log n) singular value decompositions for environments with infinite memory. Where the memory can be truncated after nc time steps, a nominal scaling O(nc log nc) is found, which is independent of n. This improved scaling is enabled by identifying process tensors with repeatable blocks. To demonstrate the power and utility of our approach, we provide three examples. (1) We calculate the fluorescence spectra of a quantum dot under both strong driving and strong dot-phonon couplings, a task requiring simulations over millions of time steps, which we are able to perform in minutes. (2) We efficiently find process tensors describing superradiance of multiple emitters. (3) We explore the limits of our algorithm by considering coherence decay with a very strongly coupled environment. The observed computation time is not necessarily proportional to the number of singular value decompositions because the matrix dimensions also depend on the number of time steps. Nevertheless, quasilinear and sublinear scaling of computation time is found in practice for a wide range of parameters. While there are instances where existing methods can achieve comparable nominal scaling by precalculating effective propagators for time-independent or periodic system Hamiltonians, process tensors contain all the information needed to extract arbitrary multitime correlation functions of the system when driven by arbitrary time-dependent system Hamiltonians. The algorithm we present here not only significantly extends the scope of numerically exact techniques to open quantum systems with long memory times, but it also has fundamental implications for the simulation complexity of tensor network approaches.

Published by the American Physical Society
2024
Corporate governance and Islamic bank risk – do the directors’ and the Shariah board’s diversity attributes matter?
Authors: Mukhibad Hasan , Setiawan Doddy , Aryani Y. Anni , Falikhatun Falikhatun
Published: February 2024

Purpose

This study aims to investigate the effect of the diversity of the board of directors (BOD) and the shariah supervisory board (SSB) on credit risk, insolvency, operations, reputation, rate of deposit return risk (RDRR) and equity-based financing risk (EBFR) of Islamic banks (IB).

Design/methodology/approach

The study uses 68 IBs from 19 countries covering 2009 to 2019. BOD and SSB diversity attributes data were hand-collected from the annual reports. Financial data were collected from the bankscope database. The robustness test and two-step system generalized method of moment estimation technique were used to address potential endogeneity issues.

Findings

This study provides evidence that diversity in the experience and cross-membership of board members decreases the risk. Gender diversity increases the risk, but the BOD’s education level diversity has no relationship with risk. More interestingly, influences in the experience and cross-membership of the SSB’s members positively influence risk. However, members’ education levels and gender diversity have not been proven to affect risk.

Practical implications

The paper recommends that Islamic banking authorities play a stronger role and make a greater effort in driving corporate governance reform. Also, determining individual characteristics of the board is a requirement to become a member of a BOD or an SSB.

Originality/value

This paper expands the commitment literature through the diversity of the BOD’s and the SSB’s members in terms of their education levels, experience, cross-membership and gender. This study expands the list of potential risks for IBs, by including the RDRR and EBFR.
Entropy generation in a partially heated hybrid nanofluid saturated wavy porous cavity
Authors: Barman Prabir , Pentyala Srinivasa Rao , Rathish Kumar B.V.
Published: February 2024

Purpose

A porous cavity flow field generates entropy owing to energy and momentum exchange within the fluid and at solid barriers. The heat transport and viscosity effects on fluid and solid walls irreversibly generate entropy. This numerical study aims to investigate convective heat transfer together with entropy generation in a partially heated wavy porous cavity filled with a hybrid nanofluid.

Design/methodology/approach

The governing equations are nondimensionalized and the domain is transformed into a unit square. A second-order finite difference method is used to have numerical solutions to nondimensional unknowns such as stream function and temperature. This numerical computation is conducted to explore a wide range of regulating parameters, e.g. hybrid nano-particle volume fraction (σ = 0.1%, 0.33%, 0.75%, 1%, 2%), Rayleigh–Darcy number (Ra = 10, 102, 103), dimensionless length of the heat source (ϵ = 0.25, 0.50,1.0) and amplitude of the wave (a = 0.05, 0.10, 0.15) for a number of undulations (N = 1, 3) per unit length.

Findings

A thorough analysis is conducted to analyze the effect of multiple factors such as thermal convective forces, heat source, surface corrugation factors, nanofluid volume fraction and other parameters on entropy generation. The flow and temperature fields are studied through streamlines and isotherms. The average Bejan number suggested that entropy generation is entirely dominated by irreversibility due to heat transport at Ra = 10, and the irreversibility due to the viscosity effect is severe at Ra = 103, but the increment in s augments irreversibility due to the viscosity effect over the heat transport at Ra = 102.

Originality/value

To the best of the authors’ knowledge, this numerical study, for the first time, analyzes the influence of surface corrugation on the entropy generation related to the cooling of a partial heat source by the convection of a hybrid nanofluid.
Does economic and policy uncertainty impact corporate policies? Evidence from India
Authors: Ramesh Vishnu K.
Published: February 2024

Purpose

This study aims to examine the role of economic political uncertainty (EPU) on various corporate policies, namely, cash reserves, investment, capital structure and operating activities of Indian listed firms.

Design/methodology/approach

To assess the influence of policy-related uncertainties, the author uses the India-specific EPU news-based index constructed by Baker et al. (2016) as a proxy for policy uncertainties. This study uses data from listed Indian firms spanning the period 2003 to 2019. The author uses panel regression models with firm-fixed effects to analyze the impact of EPU on corporate policies, including cash reserves, leverage and CAPEX, while considering key control variables.

Findings

In response to heightened EPU, firms tend to increase their cash reserves, curtail their investment activities and favour secured financing options. Notably, this study aligns with the “real options” framework, demonstrating that firms with substantial investment irreversibility significantly reduce their capital expenditures during periods of elevated EPU. Additionally, the results reveal that rising EPU corresponds to heightened borrowing costs and increased operating expenses for firms.

Originality/value

In contrast to prior research that predominantly investigated the impact of EPU on the decisions of listed firms in developed markets, this study delves into the role of EPU on corporate policies among listed firms in India. This focus is particularly relevant, given the significant policy changes that have transpired in the Indian business landscape in recent years.