bluuebunny/crossref_metadata_2025 huggingface dataset:
Insight to the influence of alkali treatment on mechanical and tribological properties of a novel carbon/jute hybrid porcine filled polyester composite
Authors: Dikshit Iti , Bhushan Gian , Kamal Batra Neel , Singh Ravinder Pal , Singh Gurminder
Published: January 2024

Growing environmental concern as a result of increased waste has encouraged a more sustainable and environmentally friendly approach to material creation. With this in consideration, a polyester-based hybrid composite was developed in this research, featuring infill composed of pig bone powder and carbon and jute fiber reinforcement. Tensile strength, impact strength, and specific wear of jute fiber treated with alkali solution with varied sodium hydroxide (NaOH) percentages (0, 5, 10, 15) were investigated. The investigations were carried out in accordance with ASTM guidelines. To examine the effect of alkali treatment on jute fiber, energy dispersion spectroscopy and Fourier transform infrared spectroscopy were performed. Following the experiment, the fracture analysis was carried out by examining the scanning electron microscopic pictures of the material. The study discovered that alkali treatment of jute fiber resulted in the elimination of hemicellulose, which considerably adds to the improvement of the composite's performance characteristics. In comparison to the untreated fiber, 15% NaOH-treated composite enhanced tensile strength and specific wear by 35% and 45%, respectively.
Gpnmb silencing protects against hyperoxia-induced acute lung injury by inhibition of mitochondrial-mediated apoptosis
Authors: Wang Xiaoqin , Qin Song , Ren Yingcong , Feng Banghai , Liu Junya , Yu Kun , Yu Hong , Liao Zhenliang , Mei Hong , Tan Mei
Published: January 2024

Background: Hyperoxia-induced acute lung injury (HALI) is a complication to ventilation in patients with respiratory failure, which can lead to acute inflammatory lung injury and chronic lung disease. The aim of this study was to integrate bioinformatics analysis to identify key genes associated with HALI and validate their role in H2O2-induced cell injury model.

Methods: Integrated bioinformatics analysis was performed to screen vital genes involved in hyperoxia-induced lung injury (HLI). CCK-8 and flow cytometry assays were performed to assess cell viability and apoptosis. Western blotting was performed to assess protein expression.

Results: In this study, glycoprotein non-metastatic melanoma protein B ( Gpnmb) was identified as a key gene in HLI by integrated bioinformatics analysis of 4 Gene Expression Omnibus (GEO) datasets (GSE97804, GSE51039, GSE76301 and GSE87350). Knockdown of Gpnmb increased cell viability and decreased apoptosis in H2O2-treated MLE-12 cells, suggesting that Gpnmb was a proapoptotic gene during HALI. Western blotting results showed that knockdown of Gpnmb reduced the expression of Bcl-2 associated X (BAX) and cleaved-caspase 3, and increased the expression of Bcl-2 in H2O2 treated MLE-12 cells. Furthermore, Gpnmb knockdown could significantly reduce reactive oxygen species (ROS) generation and improve the mitochondrial membrane potential.

Conclusion: The present study showed that knockdown of Gpnmb may protect against HLI by repressing mitochondrial-mediated apoptosis.
Anti-S Antibodies Against SARS-CoV-2 Infection Among Four Types of Vaccines in Malaysia
Authors: Lodz Noor Aliza , Mat Tamizi Nurdiyana Farhana , Abd Mutalip Mohd Hatta , Ganapathy Shubash Shander , Lin Chong Zhuo , Ismail Rohani , Ahmad Noor Ani
Published: January 2024

Monitoring SARS-CoV-2 antibody levels can provide insights into a person’s immunity to COVID-19 and inform decisions about vaccination and public health measures. Anti-S may be useful as an indicator of an effective immune response. Thus, we conducted this study that aimed to determine the immune response of anti-S antibodies against SARS-CoV-2 for all the vaccine types over time among adult recipients in Malaysia and to determine the associated factors. This study was a cohort that recruited 2513 respondents aged 18 years and above from June to December 2021. Each participant was followed-up for 1-year period from the initial vaccine dose (baseline). We found that the anti-S antibody generally increased for all vaccine types and peaked at two weeks after the second dose vaccination, with Pfizer recipients having the highest median of 100 (100.00-100.00). During the third-month follow-up, the seropositivity of anti-S antibody and the median level decreased for all vaccines. We found that type of vaccines, comorbid status, infection, and booster status were significantly associated with the anti-S antibody level after one year.
Abbe Flap Division Before Two Weeks’ Time: Harmful or Advantageous?
Authors: Muller John N. , Diaz Allison , Flores Roberto L. , Staffenberg David A.
Published: January 2024

Introduction

The Abbe flap is a standard intervention to treat upper lip deformities in patients with bilateral cleft lip. This two-stage procedure requires a 2 to 3-week period in which the superior and inferior lips remain connected. This study evaluates the safety of Abbe flap division and inset prior to 14 days’ time.

Materials and Methods

A single institution, 8-year review of all patients with a bilateral cleft lip who underwent Abbe flap reconstruction was performed. Patients were classified into two groups: those whom division was performed 14 days or later and those with division earlier than 14 days.

Results

A total of 26 patients were identified. Patients who underwent Abbe flap division in less than 14 days (n = 10) demonstrated an average time to division of 9.7 days (range 7–13 days) with no evidence of flap loss, wound breakdown or infection. Patients who underwent Abbe flap division within 14 days or more (n = 16) demonstrated an average time to division of 15 days with four minor complications and no flap loss.

Conclusion

Dividing the Abbe flap after the first postoperative week appears to be safe and without additional risk to flap loss or wound breakdown. A shorter time to Abbe flap division may decrease the burden of care on patients and their caregivers.
EBV-Associated Smooth Muscle Tumors With Autoimmune Hemolytic Anemia and Hepatitis B Infection: Report of a Previously Undescribed Neoplasm With Review
Authors: Zheng Qiaoli , Wang Chaofu , Zhang Yuxiu , Xu Haimin , Yuan Fei , Yi Hongmei
Published: January 2024

Epstein-Barr virus-associated smooth muscle tumor (EBV-SMT) is rare in adults. The presence of intratumoral T lymphocytes and primitive rounded cells characterized this neoplasm. We report a 24-year-old Chinese man who developed EBV-SMT in the right adrenal gland with hepatitis B infection and autoimmune hemolytic anemia without a history of HIV infection, primary immune deficiency, organ transplantation, or malignant tumor. This patient had an unknown immunodeficient state. EBV-SMTs are commonly located in the liver, lung, and gastrointestinal tract but rarely in the adrenal gland. We reviewed 10 reported literature on EBV-SMT in the adrenal gland. It is imperative to distinguish EBV-SMT from conventional somatic smooth muscle tumors. The discovery of EBV-SMT forces the clinician to conduct a thorough evaluation of immune function and immune status surveillance, and these patients are vulnerable to subsequent malignant tumors.
Impact of age, obesity, and renal impairment on outcomes after autologous stem cell transplantation for patients with newly diagnosed multiple myeloma
Authors: Gaffney Kelly J , Bakos Jonathan K. , Velayati Arash , Davis James A. , Thurlapati Aswani , Weeda Erin , Maldonado Andy , Granger Katelynn , Butcher Coleen , Herrington Taylor , Smith Deidra , Green Kimberly , Hess Brian T , Hashmi Hamza
Published: January 2024

Introduction

There remains a need to determine whether certain subgroups of newly diagnosed multiple myeloma (NDMM) derive the same benefit from high-dose chemotherapy–autologous stem cell transplant (HDT-ASCT). We describe our institutional experience highlighting the impact of age, obesity, and renal impairment on outcomes after HDT-ASCT for patients with NDMM in a real-world setting.

Methods

A total of 449 consecutive patients were included in this retrospective analysis.

Results

No difference in median progression free survival or overall survival was seen for patients with age > 65, body mass index (BMI) > 30 kg/m2, or estimated glomerular filtration rate < 60 mL/min/1.73 m2 when compared to those without these characteristics. From a safety standpoint, there were no differences in the incidence of transplant-related mortality or secondary malignancy among subgroups.

Conclusion

For patients with NDMM undergoing HDT-ASCT, there is no difference in outcomes based on age, BMI, or renal function, and the presence of one or more of these factors should not preclude patients from HDT-ASCT.
What Triggers Customer Curiosity? Exploring the Role of Branded Content Experience Design on Customer Response
Authors: Lee Seonjeong (Ally)
Published: January 2024

Various branded content is developed on social media; however, not all branded content stimulates customer curiosity. Based on the uses and gratification theory as a theoretical background, this paper investigates antecedents and outcomes of customer curiosity on social media. Using a self-administered, online survey, data were collected from customers who used hotel social media platforms within the previous 12 months. Results identified that utilitarian, social bonding, and aesthetic branded content experiences positively influenced customers’ curiosity, which then influenced customers’ brand engagement and purchase intentions. Results of this study contribute to branded content, customer curiosity, and experience design literature. Results also provide suggestions to industry practitioners by exploring the role of branded content experiences on customers’ emotional and behavioral responses.
The Sustainable Rhythm of Destination Popularity: A Song of Local Well-Being and Lasting Charm
Authors: Kim Hyoeun , Yoon Junho , Nicolau Juan Luis
Published: January 2024

Destination popularity has long-term effects on the local community’s quality of life and the destination’s attractiveness. This study examines the impact of environmental, economic, and social factors on destination popularity, while introducing a new sustainable tourism index as a novel approach to measuring sustainability in destinations. The study acknowledges that, although popular destinations generate high revenue, excessive popularity can have negative consequences for long-term destination appeal. Unlike the traditional country-level and qualitative approach, the proposed index relies on open-source data, allowing for frequent updates at the local level. By analyzing 2,164 U.S. counties, the study reveals a positive relationship between economic, environmental, and social factors and destination popularity, with variation in the magnitude of these effects. The study also presents examples of potential applications for the proposed index, offering valuable insights into the complex dynamics of destination popularity, and providing a practical tool for assessing sustainable tourism.
COVID-19 vaccination among health care workers in Finland: coverage, perceptions and attitudes
Authors: Hämäläinen Aleksi , Patovirta Riitta-Liisa , Vuorinen Sakari , Leppäaho-Lakka Jaana , Kilpinen Sanna , Sieberns Jennifer , Ruotsalainen Eija , Koivula Irma , Hämäläinen Sari
Published: January 2024

Aims:

In this study, we examined the voluntary COVID-19 vaccine coverage among health care workers (HCWs) working in close patient contact. HCWs’ beliefs about COVID-19 infection, their opinions of vaccination and reasons for having or declining the COVID-19 vaccination were also evaluated.

Methods:

In October 2021, a cross-sectional observational study was carried out in five hospitals in Central and Eastern Finland. The anonymous and voluntary survey was targeted at 5120 doctors and nurses working in close patient contact.

Results:

Some 1837 responses were included in the study. Ninety-seven per cent of the respondents had received at least one COVID-19 vaccine and 68% of the respondents agreed that all HCWs working in close patient contact should be vaccinated against COVID-19. Vaccination coverage and support for vaccination were higher among older HCWs and doctors. HCWs’ main reasons for having the COVID vaccine were willingness to protect themselves, their family and their patients from COVID-19. Concerns about adverse reactions to the COVID-19 vaccine was the main reason for declining it.

Conclusions:

The overall COVID-19 vaccination coverage and support for vaccinations among HCWs working in close patient contact were high without actual mandatory policies being introduced. Prioritising HCWs for COVID-19 vaccinations and widespread vaccine availability, as well as low general vaccine hesitancy and high seasonal influenza vaccination coverage among the study population were check marks in achieving high COVID-19 vaccination coverage rapidly.
A systematic review of the social impact of diseases in Nordic countries
Authors: Seo Ahreum , Chang Angela Y.
Published: January 2024

Background:

We review the literature on the social impacts of diseases, defined as the social consequences of having a disease on the people around the patient, such as spouses, caregivers and offspring. The two objectives of this study are to summarise the social outcomes commonly associated with diseases and to compare the social impact across a range of diseases.

Methods:

A systematic review of the social impact of disease in Nordic countries was conducted using PubMed, PsycINFO and Google Scholar (PROSPERO registration number CRD42022291796). All articles that met the inclusion criteria were reviewed. We tabulated all outcomes and diseases studied, and synthesised the evidence based on the perspectives of patients, spouse/caregiver and offspring.

Results:

A total of 135 studies met the eligibility criteria, covering 76 diseases and 39 outcomes. From the patient’s perspective, diseases impact divorce and marriage rates, social functioning, likelihood of committing a crime and being a victim of crime. From the caregiver’s perspective, diseases affect their health-related quality of life and physical and psychological health. From the offspring’s perspective, diseases impact their development, health and social adversities in later life. Diseases generally had negative social impacts, but there were some diseases associated with positive impacts.

Conclusions:

The review provides a useful summary and gross comparison of the social impact of different diseases. The social impact of diseases can be large and significant. Thus, it should be considered when policymakers are setting priorities across disease areas.
On the influence of an energy harvesting device on a dynamical system
Authors: Amer TS , Arab A , Galal AA
Published: January 2024

This article studies the motion of a three degrees-of-freedom (DOF) dynamical system, which consists of two parts, a dynamic part, and an electromagnetic harvesting device. The composition of the system depends on the magnet oscillating in the coil of this device. An electric potential is exerted because of the electromotive force to obtain energy harvesting (EH). Lagrange's equations (LE) are used to derive the system’s equations of motion (EOM), which are solved analytically up to a third-order of approximation using the multiple-scales method (MSM). These solutions are considered novel, in which the mentioned method is applied to a novel dynamical system. The gained are confirmed through comparison with the numerical solutions of the EOM to reveal a high degree of consistency. To establish the system’s solvable conditions and modulation equations (ME), three scenarios of primary external resonance are investigated simultaneously. Certain diagrams of time histories for the amplitudes and phases of the examined dynamical system are plotted to show their behaviors at any given instance of time. The Routh–Hurwitz criteria (RHC) are used to establish the stability and instability regions in light of the graphs of resonance response curves. The presence of an energy harvester in dynamic devices helps us to convert vibrational motion into electrical energy that can be exploited in several applications in a variety of daily tasks, including structural and environmental monitoring, military applications, space exploration, and remote medical sensing.
Punishment is purple: The political economy of prison building
Authors: Eason John M , Campbell Mary E , Ghasemi Benjamin , Huey Eileen
Published: January 2024

The United States is unique among rich countries in the world in its level of contemporary mass incarceration, a massive social change that has reshaped the nature of inequality and social mobility. We have more than tripled the number of prison facilities since 1970. Despite employing nearly 450,000 corrections officers, occupying a land mass of roughly 600 square miles, and costing conservatively $30 billion to build, this massive public works project has transformed the American countryside virtually unnoticed, with nearly 70% of U.S. facilities being built in rural communities. We suggest that mass incarceration—more than 2 million locked up annually—was not possible without the transformation of the American countryside through the prison boom—the increase from roughly 500 to nearly 1700 carceral facilities. There is a longstanding belief that the rural town leaders and politicians responsible for the prison boom are almost exclusively white, male, Republicans. We explore the political, social, and economic influences of prison building across states, regions, and cities/towns. Using multilevel modeling, we find that racial and economic disadvantage predicts prison building in towns, and party affiliation of state legislatures predicts prison building across different periods of the prison boom. While others find a link between Republican Party strength in state legislatures and mass incarceration, our findings suggest that prison building, like other types of punishment, results from bipartisan political support for the state's ability to punish. We conclude by advancing an expanded theoretical approach to the prison boom.
Chinese expert consensus on clinical practice of MET detection in non-small cell lung cancer
Authors: Bai Qianming , Shi Xiaohua , Zhou Xiaoyan , Liang Zhiyong , Lu Shun , Wu Yilong
Published: January 2024

Mesenchymal epithelial transition (MET) factor alteration in non-small cell lung cancer (NSCLC) includes MET exon 14 skipping alteration (METex14 skipping), MET gene amplification, MET gene mutation (mainly kinase domain mutation), MET gene fusion, and MET protein overexpression. The incidence of METex14 skipping in patients with NSCLC is 0.9–4.0%. At present, drugs targeting METex14 skipping have been approved in China and other countries like Japan and USA. Patients with advanced NSCLC should undergo testing, including METex14 skipping, to screen the population with benefit from targeted therapy with MET inhibitors. The incidence of de novo MET gene amplification in NSCLC patients is 1–5%, the incidence of acquired MET gene amplification in epidermal growth factor receptor tyrosine kinase inhibitor (TKI)-resistant patients is 5–50%, and the incidence in anaplastic lymphoma kinase (ALK) TKI-resistant patients is about 13%; the incidence of MET protein overexpression in NSCLC patients is 13.7–63.7%. Several clinical trials on MET gene amplification and MET protein overexpression are ongoing, which have demonstrated their important guiding significance as biomarkers in the clinical treatment with MET inhibitors. Accurate detection of MET alterations is a prerequisite for MET inhibitor therapy. Since there are many types of MET alterations and related testing methods, as well as many problems and challenges during clinical testing, further sorting and standardization are required. Combined with clinical practice experience, literature review, and expert discussion, the writing group developed this consensus on the three main types of MET alterations (METex14 skipping, MET gene amplification, and MET protein overexpression) in order to guide the practical applications of clinical MET testing.
Short-term outcomes of combined therapy with sirolimus and interferon-alpha 2b for advanced hepatic epithelioid hemangioendothelioma
Authors: Liu Xiaolei , Zhou Ruiquan , Liu Liguo , Si Shuang , Yang Shiwei , Han Dongdong , Tan Haidong
Published: January 2024

Background:

Hepatic epithelioid hemangioendothelioma (EHE) is an extremely rare tumor, and no standard therapy has been established yet.

Objectives:

The aim of this study was to investigate the short-term results of combined therapy with sirolimus and interferon-alpha 2b (IFN-a 2b) (SI therapy).

Methods:

From January 2022 to April 2023, 40 patients histologically diagnosed with hepatic EHE and progressive disease received SI therapy. All patients were regularly evaluated for the safety and efficacy of the SI therapy. Patients who received SI therapy for <3 months without a tumor status evaluation after treatment were excluded.

Results:

Twenty-nine patients with hepatic EHE were included in this study. The Eastern Cooperative Oncology Group (ECOG) performance status was 0 in 19 (65.5%) patients and 1 in 10 (34.5%) patients. The median duration of the SI therapy was 8 months (range, 3–15 months). Twenty-three (79.3%) patients showed a decrease in tumor size, including 11 (37.9%) patients who achieved a partial response and one (3.4%) who achieved a complete response; the objective response rate was 41.4%. Stable disease was observed in 13 (44.8%) patients, with a disease control rate of 86.2%. Adverse events (AES) were observed in 18 patients, including leukopenia (31.0%), oral ulcers (13.8%), and liver injury (10.3%). No severe (grade ⩾ 3) AEs were recorded, and SI therapy was not interrupted for any patient due to AEs.

Conclusion:

Sirolimus and IFN-a 2b may have synergistic effects in the treatment of hepatic EHE. SI therapy is a safe and effective treatment for hepatic EHE patients with good ECOG performance status.
Peer-Led Groups in Sexual Assault Prevention Programming: Myth Adherence and Self-Defense Efficacy within Gender and Race
Authors: Dempster Darleen Patricia , Koon-Magnin Sarah , Preyear FeAunte , Mayo Shawna , Norrell Phillip M.
Published: January 2024

Participants ( n = 520) in a study of two on-campus peer-led sexual assault prevention programs focused on bystander intervention and risk reduction were assessed. This study focused on myth reduction, as well as self-defense self-efficacy. Demographics allowed for within-group comparisons along gender and race. Among men who attended Bro Code, Black men had significantly lower sexual assault myth adherence on many rape myths than the control group, not true of white men. Those women who attended Girls Night Out (GNO) had significantly lower sexual assault myth adherence than the control group. While greater reductions in myth adherence were seen in white women than among Black women, Black women had significantly lower overall sexual assault myth adherence (in both control and sample). As a side note, we found that women who attended GNO had lower general intimate partner violence myth acceptance in addition to lower sexual assault myth acceptance, with some variation on individual myths. Finally, those women who attended self-defense training were significantly more likely to endorse self-defense self-efficacy. Results were then explored through the lens of cultural, gender, intersectional, and community-based contexts. Future research needs and implications are discussed.
Unique presentation of an intramuscular abscess caused by Bacteroides pyogenes in the setting of a cat bite: A case report
Authors: Sadhwani Shaan , DiAngelis Derek , Brown Michael , Ferguson Christopher , Angerett Nathan
Published: January 2024

Cat bites are a relatively common emergency department presentation. The most common species isolated from cat bite wounds is Pasteurella multocida. In this case report, we discuss a unique case of an intramuscular abscess caused by Bacteroides pyogenes. Antibiotic resistance in Bacteroides species is a growing concern and thus should be treated with caution. We present an 81-year-old female who presented to the emergency department with left calf pain that began 3 weeks prior to the emergency department presentation. She was initially seen by her primary care provider and was prescribed oral Trimethoprim/Sulfamethoxazole and Amoxicillin/Clavulanate. Despite oral antibiotics, she began to have worsening swelling, erythema, and fevers. In the emergency department, the patient’s left calf was noticeably erythematous and tender to palpation. Lab work showed a C-reactive protein of 12.4 mg/dl, erythrocyte sedimentation rate of 38 mm/h, and white blood cell count of 15.1. Computed tomography imaging showed an irregularly shaped fluid collection at the junction of the calf musculature and upper aspect of the Achilles tendon. The decision was made to perform an operative incision and debridement on the evening of her presentation. On postoperative day 2, the wound cultures grew positive for both Pasturella multocida and Bacteroides pyogenes. She was subsequently discharged with oral Amoxicillin/Clavulanate 875 mg twice daily for 4 weeks. Further studies can be performed to identify the most efficient ways to isolate and treat this species. This case report emphasizes the importance of ordering both aerobic and anaerobic cultures and aiming antimicrobial therapy against both Pasteurella and anaerobic bacteria.
What's in This For You? What's in This For Me?: A Win-Win Perspective of Involving Study Advisory Committee Members in Palliative Care Research
Authors: Booker-Vaughns Juanita , Rosini Dawn , Batra Romilla , Chan Garrett K. , Dunn Patrick , Galvin Robert , Hopkins Ernest , Isaacs Eric , Kizzie-Gillett Constance L. , Maguire Margaret , Navarro Martha , Reddy Pidatala Neha , Vaughan William , Welsh Sally , Williams Pluscedia , Young-Brinn Angela , Van Allen Kaitlyn , Cuthel Allison M. , Liddicoat Yamarik Rebecca , Flannery Mara , Goldfeld Keith S. , Grudzen Corita R.
Published: January 2024

Study advisory committees (SACs) provide critical value to clinical trials by providing unique perspectives that pull from personal and professional experiences related to the trial's healthcare topic. The Emergency Medicine Palliative Care Access (EMPallA) study had the privilege of convening a 16-person SAC from the project's inception to completion. The study team wanted to understand the impact this project had on the SAC members. In this narrative, we use reflective dialogue to share SAC members’ lived experiences and the impact the EMPallA study has had on members both personally and professionally. We detail the (1) benefits SAC members, specifically patients, and caregivers, have had through working on this project. (2) The importance of recruiting diverse SAC members with different lived experiences and leveraging their feedback in clinical research. (3) Value of community capacity building to ensure the common vision of the clinical trial is promoted.
Staphylococcus aureusinduces drug resistance in cancer T cells in Sézary syndrome
Authors: Vadivel Chella Krishna , Willerslev-Olsen Andreas , Namini Martin R. J. , Zeng Ziao , Yan Lang , Danielsen Maria , Gluud Maria , Pallesen Emil M. H. , Wojewoda Karolina , Osmancevic Amra , Hedebo Signe , Chang Yun-Tsan , Lindahl Lise M. , Koralov Sergei B. , Geskin Larisa J. , Bates Susan E. , Iversen Lars , Litman Thomas , Bech Rikke , Wobser Marion , Guenova Emmanuella , Kamstrup Maria R. , Ødum Niels , Buus Terkild B.
Published: January 2024

Patients with Sézary syndrome (SS), a leukemic variant of cutaneous T-cell lymphoma (CTCL), are prone to Staphylococcus aureus infections and have a poor prognosis due to treatment resistance. Here, we report that S aureus and staphylococcal enterotoxins (SE) induce drug resistance in malignant T cells against therapeutics commonly used in CTCL. Supernatant from patient-derived, SE-producing S aureus and recombinant SE significantly inhibit cell death induced by histone deacetylase (HDAC) inhibitor romidepsin in primary malignant T cells from patients with SS. Bacterial killing by engineered, bacteriophage-derived, S aureus–specific endolysin (XZ.700) abrogates the effect of S aureus supernatant. Similarly, mutations in major histocompatibility complex (MHC) class II binding sites of SE type A (SEA) and anti-SEA antibody block induction of resistance. Importantly, SE also triggers resistance to other HDAC inhibitors (vorinostat and resminostat) and chemotherapeutic drugs (doxorubicin and etoposide). Multimodal single-cell sequencing indicates T-cell receptor (TCR), NF-κB, and JAK/STAT signaling pathways (previously associated with drug resistance) as putative mediators of SE-induced drug resistance. In support, inhibition of TCR-signaling and Protein kinase C (upstream of NF-κB) counteracts SE-induced rescue from drug-induced cell death. Inversely, SE cannot rescue from cell death induced by the proteasome/NF-κB inhibitor bortezomib. Inhibition of JAK/STAT only blocks rescue in patients whose malignant T-cell survival is dependent on SE-induced cytokines, suggesting 2 distinct ways SE can induce drug resistance. In conclusion, we show that S aureus enterotoxins induce drug resistance in primary malignant T cells. These findings suggest that S aureus enterotoxins cause clinical treatment resistance in patients with SS, and antibacterial measures may improve the outcome of cancer-directed therapy in patients harboring S aureus.
The demographic history and adaptation of Canarian goat breeds to environmental conditions through the use of genome-wide SNP data
Authors: Senczuk Gabriele , Macrì Martina , Di Civita Marika , Mastrangelo Salvatore , del Rosario Fresno Maria , Capote Juan , Pilla Fabio , Delgado Juan Vicente , Amills Marcel , Martínez Amparo
Published: January 2024

Background

The presence of goats in the Canary Islands dates back to the late 1st millennium BC, which coincides with the colonization by the Amazigh settlers. However, the exact geographic origin of Canarian goats is uncertain since the Amazigh peoples were distributed over a wide spatial range. Nowadays, three Canarian breeds (Palmera, Majorera and Tinerfeña) are officially recognized, along with two distinct South and North Tinerfeña ecotypes, with the South Tinerfeña and Majorera goats thriving in arid and dry semi-desertic environments and the Palmera and North Tinerfeña goats are adapted to humid and temperate areas that are influenced by trade winds. Genotypes for 224 Canarian goats were generated using the Illumina Goat single nucleotide polymorphism (SNP)50 BeadChip. By merging these data with the genotypes from 1007 individuals of African and Southern European ancestry, our aim was to ascertain the geographic origin of the Canarian goats and identify genes associated with adaptation to diverse environmental conditions.

Results

The diversity indices of the Canarian breeds align with most of those of the analyzed local breeds from Africa and Europe, except for the Palmera goats that showed lower levels of genetic variation. The Canarian breeds demonstrate a significant genetic differentiation compared to other populations, which indicates a history of prolonged geographic isolation. Moreover, the phylogenetic reconstruction indicated that the ancestry of the Canarian goats is fundamentally North African rather than West African. The ADMIXTURE and the TreeMix analyses showed no evidence of gene flow between Canarian goats and other continental breeds. The analysis of runs of homozygosity (ROH) identified 13 ROH islands while the window-based FST method detected 25 genomic regions under selection. Major signals of selection were found on Capra hircus (CHI) chromosomes 6, 7, and 10 using various comparisons and methods.

Conclusions

This genome-wide analysis sheds new light on the evolutionary history of the four breeds that inhabit the Canary Islands. Our findings suggest a North African origin of the Canarian goats. In addition, within the genomic regions highlighted by the ROH and FST approaches, several genes related to body size and heat tolerance were identified.
Mechanisms by which silencing long-stranded noncoding RNA KCNQ1OT1 alleviates myocardial ischemia/reperfusion injury (MI/RI)-induced cardiac injury via miR-377-3p/HMOX1
Authors: Tan Tongcai , Tu Liang , Yu Yanmei , He MinJie , Zhou Xingchao , Yang Lei
Published: January 2024

Background

The key complication of myocardial infarction therapy is myocardial ischemia/reperfusion injury (MI/RI), and there is no effective treatment. The present study elucidates the mechanism of action of lncRNA KCNQ1OT1 in alleviating MI/RI and provides new perspectives and therapeutic targets for cardiac injury-related diseases.

Methods

An ischemia/reperfusion (I/R) injury model of human adult cardiac myocytes (HACMs) was constructed, and the expression of KCNQ1OT1 and miR-377-3p was determined by RT‒qPCR. The levels of related proteins were detected by western blot analysis. Cell proliferation was detected by a CCK-8 assay, and cell apoptosis and ROS content were determined by flow cytometry. SOD and MDA expression as well as Fe2+ changes were detected by related analysis kits. The target binding relationships between lncRNA KCNQ1OT1 and miR-377-3p as well as between miR-377-3p and heme oxygenase 1 (HMOX1) were verified by a dual-luciferase reporter gene assay.

Results

Myocardial ischemia‒reperfusion caused oxidative stress in HACMs, resulting in elevated ROS levels, increased Fe2+ levels, decreased cell viability, and increased LDH release (a marker of myocardial injury), and apoptosis. KCNQ1OT1 and HMOX1 were upregulated in I/R-induced myocardial injury, but the level of miR-377-3p was decreased. A dual-luciferase reporter gene assay indicated that lncRNA KCNQ1OT1 targets miR-377-3p and that miR-377-3p targets HMOX1. Inhibition of HMOX1 alleviated miR-377-3p downregulation-induced myocardial injury. Furthermore, lncRNA KCNQ1OT1 promoted the level of HMOX1 by binding to miR-377-3p and aggravated myocardial injury.

Conclusion

LncRNA KCNQ1OT1 aggravates ischemia‒reperfusion-induced cardiac injury via miR-377-3P/HMOX1.
The molecular mechanism of MiR-26a-5p regulates autophagy and activates NLRP3 inflammasome to mediate cardiomyocyte hypertrophy
Authors: Tang Li-qun , Wang Wei , Tang Qi-feng , Wang Ling-ling
Published: January 2024

Objective

Many studies have found that miR-26a-5p plays an essential role in the progression of pathological cardiac hypertrophy, however, there is still no evidence on whether miR-26a-5p is related to the activation of autophagy and NLRP3 inflammasome. And the mechanism of miR-26a-5p and NLRP3 inflammasome aggravating pathological cardiac hypertrophy remain unclear.

Methods

Cardiomyocytes were treated with 200µM PE to induce cardiac hypertrophy and intervened with 10mM NLRP3 inhibitor INF39. In addition, we also used the MiR-26a-5p mimic and inhibitor to transfect PE-induced cardiac hypertrophy. RT-qPCR and western blotting were used to detect the expressions of miR-26a-5p, NLRP3, ASC and Caspase-1 in each group, and we used α-SMA immunofluorescence to detect the change of cardiomyocyte area. The expression levels of autophagy proteins LC3, beclin-1 and p62 were detected by western blotting. Finally, we induced the SD rat cardiac hypertrophy model through aortic constriction (TAC) surgery. In the experimental group, rats were intervened with MiR-26a-5p mimic, MiR-26a-5p inhibitor, autophagy inhibitor 3-MA, and autophagy activator Rapamycin.

Results

In cell experiments, we observed that the expression of miR-26a-5p was associated with cardiomyocyte hypertrophy and increased surface area. Furthermore, miR-26a-5p facilitated autophagy and activated the NLRP3 inflammasome pathway, which caused changes in the expression of genes and proteins including LC3, beclin-1, p62, ACS, NLRP3, and Caspase-1. We discovered similar outcomes in the TAC rat model, where miR-26a-5p expression corresponded with cardiomyocyte enlargement and fibrosis in the cardiac interstitial and perivascular regions. In conclusion, miR-26a-5p has the potential to regulate autophagy and activate the NLRP3 inflammasome, contributing to the development of cardiomyocyte hypertrophy.

Conclusion

Our study found a relationship between the expression of miR-26a-5p and cardiomyocyte hypertrophy. The mechanism behind this relationship appears to involve the activation of the NLRP3 inflammasome pathway, which is caused by miR-26a-5p promoting autophagy. Targeting the expression of miR-26a-5p, as well as inhibiting the activation of autophagy and the NLRP3 inflammasome pathway, could offer additional treatments for pathological cardiac hypertrophy.
The moderating effect of mental health and health insurance ownership on the relationships between physical multimorbidity and healthcare utilisation and catastrophic health expenditure in India
Authors: Berger Finja , Anindya Kanya , Pati Sanghamitra , Ghosal Shishirendu , Dreger Stefanie , Lee John Tayu , Ng Nawi
Published: January 2024

Background

The current demographic transition has resulted in the growth of the older population in India, a population group which has a higher chance of being affected by multimorbidity and its subsequent healthcare and economic consequences. However, little attention has been paid to the dual effect of mental health conditions and physical multimorbidity in India. The present study, therefore, aimed to analyse the moderating effects of mental health and health insurance ownership in the association between physical multimorbidity and healthcare utilisation and catastrophic health expenditure (CHE).

Methods

We analysed the Longitudinal Aging Study in India, wave 1 (2017–2018). We determined physical multimorbidity by assessing the number of physical conditions. We built multivariable logistic regression models to determine the moderating effect of mental health and health insurance ownership in the association between the number of physical conditions and healthcare utilisation and CHE. Wald tests were used to evaluate if the estimated effects differ across groups defined by the moderating variables.

Results

Overall, around one-quarter of adults aged 45 and above had physical multimorbidity, one-third had a mental health condition and 20.5% owned health insurance. Irrespective of having a mental condition and health insurance, physical multimorbidity was associated with increased utilisation of healthcare and CHE. Having an additional mental condition strengthened the adverse effect of physical multimorbidity on increased inpatient service use and experience of CHE. Having health insurance, on the other hand, attenuated the effect of experiencing CHE, indicating a protective effect.

Conclusions

The coexistence of mental health conditions in people with physical multimorbidity increases the demands of healthcare service utilisation and can lead to CHE. The findings point to the need for multidisciplinary interventions for individuals with physical multimorbidity, ensuring their mental health needs are also addressed. Our results urge enhancing health insurance schemes for individuals with mental and physical multimorbidity.
Genetic diversity and seroprevalence of Toxoplasma gondii in COVID‑19 patients; a first case-control study in Iran
Authors: Hasanzadeh Mehdi , Ahmadpour Ehsan , Mahami-Oskouei Mahmoud , Musavi Saeed , Parsaei Mahdi , Sarafraz Nazila , Spotin Adel
Published: January 2024

Background

Toxoplasmosis is a serious or life-threatening disease in immunosuppressed patients and pregnant women. This study examined the likely association between Toxoplasma gondii infection and COVID-19 patients with moderate illness.

Methods

Seventy blood samples were collected from patients at the Health Reference Laboratory of Tabriz, Northwest Iran from April 2021 to September 2021. In addition, 70 healthy subjects of the same age (37 ± 15 years) and sex distribution were ethnically matched. Sera samples were examined for the detection of anti-Toxoplasma antibodies using ELISA. Nested-PCR targets were amplified based on the B1 and GRA6 genes. GRA6 amplicons were subjected to sequencing and phylogenetic analysis.

Results

The seroprevalence of toxoplasmosis based on IgG titer was 35.7% in the COVID‑19 patients and 27.1% in the control group, representing not to be associated with the Toxoplasma seropositivity in COVID‑19 patients (P = 0.18) compared to healthy subjects. Anti-T. gondii IgM was not found in any of the patients and healthy individuals. According to PCR amplification of the B1 and GRA6 genes, the frequency of T. gondii in COVID-19 patients was 14.2% (10/70). However, no T. gondii infection was detected in the healthy group. The CD4+T cell count was relatively lower in toxoplasmosis-infected patients (430–450 cells/mm3) than in control group (500–1500 cells/mm3). High genetic diversity (Hd: 0.710) of the type I strain of T. gondii was characterized in the patients. Present results showed that consumption of raw vegetables and close contact with stray cats can increase the transmission of T. gondii to COVID-19 patients (P < 0.01).

Conclusions

The current study revealed that T. gondii type I infection is unequivocally circulating among the COVID-19 patients in Tabriz; However, no significant association was observed between the occurrence of Toxoplasma and the severity of COVID-19. To make more accurate health decisions, multicenter investigations with a larger sample size of different ethnic groups of the Iranian population are needed.
Mortality and mode of dialysis: meta-analysis and systematic review
Authors: Chander Subhash , Luhana Sindhu , Sadarat FNU , Parkash Om , Rahaman Zubair , Wang Hong Yu , Kiran FNU , Lohana Abhi Chand , Sapna FNU , Kumari Roopa
Published: January 2024

Background

The global use of kidney replacement therapy (KRT) has increased, mirroring the incidence of acute kidney injury and chronic kidney disease. Despite its growing clinical usage, patient outcomes with KRT modalities remain controversial. In this meta-analysis, we sought to compare the mortality outcomes of patients with any kidney disease requiring peritoneal dialysis (PD), hemodialysis (HD), or continuous renal replacement therapy (CRRT).

Methods

The investigation was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). PubMed (MEDLINE), Cochrane Library, and Embase databases were screened for randomized trials and observational studies comparing mortality rates with different KRT modalities in patients with acute or chronic kidney failure. A random-effects model was applied to compute the risk ratio (RR) and 95% confidence intervals (95%CI) with CRRT vs. HD, CRRT vs. PD, and HD vs. PD. Heterogeneity was assessed using I2 statistics, and sensitivity using leave-one-out analysis.

Results

Fifteen eligible studies were identified, allowing comparisons of mortality risk with different dialytic modalities. The relative risk was non-significant in CRRT vs. PD [RR = 0.95, (95%CI 0.53, 1.73), p = 0.92 from 4 studies] and HD vs. CRRT [RR = 1.10, (95%CI 0.95, 1.27), p = 0.21 from five studies] comparisons. The findings remained unchanged in the leave-one-out sensitivity analysis. Although PD was associated with lower mortality risk than HD [RR = 0.78, (95%CI 0.62, 0.97), p = 0.03], the significance was lost with the exclusion of 4 out of 5 included studies.

Conclusion

The current evidence indicates that while patients receiving CRRT may have similar mortality risks compared to those receiving HD or PD, PD may be associated with lower mortality risk compared to HD. However, high heterogeneity among the included studies limits the generalizability of our findings. High-quality studies comparing mortality outcomes with different dialytic modalities in CKD are necessary for a more robust safety and efficacy evaluation.
Identification of clinical prognostic factors and analysis of ferroptosis-related gene signatures in the bladder cancer immune microenvironment
Authors: Ma Jiafu , Hu Jianting , Zhao Leizuo , Wu Zixuan , Li Rongfen , Deng Wentao
Published: January 2024

Background

Bladder cancer (BLCA) is a prevalent malignancy affecting the urinary system and poses a significant burden in terms of both incidence and mortality rates on a global scale. Among all BLCA cases, non-muscle invasive bladder cancer constitutes approximately 75% of the total. In recent years, the concept of ferroptosis, an iron-dependent form of regulated cell death marked by the accumulation of lipid peroxides, has captured the attention of researchers worldwide. Nevertheless, the precise involvement of ferroptosis-related genes (FRGs) in the anti-BLCA response remains inadequately elucidated.

Methods

The integration of BLCA samples from the TCGA and GEO datasets facilitated the quantitative evaluation of FRGs, offering potential insights into their predictive capabilities. Leveraging the wealth of information encompassing mRNAsi, gene mutations, CNV, TMB, and clinical features within these datasets further enriched the analysis, augmenting its robustness and reliability. Through the utilization of Lasso regression, a prediction model was developed, enabling accurate prognostic assessments within the context of BLCA. Additionally, co-expression analysis shed light on the complex relationship between gene expression patterns and FRGs, unraveling their functional relevance and potential implications in BLCA.

Results

FRGs exhibited increased expression levels in the high-risk cohort of BLCA patients, even in the absence of other clinical indicators, suggesting their potential as prognostic markers. GSEA revealed enrichment of immunological and tumor-related pathways specifically in the high-risk group. Furthermore, notable differences were observed in immune function and m6a gene expression between the low- and high-risk groups. Several genes, including MYBPH, SOST, SPRR2A, and CRNN, were found to potentially participate in the oncogenic processes underlying BLCA. Additionally, CYP4F8, PDZD3, CRTAC1, and LRTM1 were identified as potential tumor suppressor genes. Significant discrepancies in immunological function and m6a gene expression were observed between the two risk groups, further highlighting the distinct molecular characteristics associated with different prognostic outcomes. Notably, strong correlations were observed among the prognostic model, CNVs, SNPs, and drug sensitivity profiles.

Conclusions

FRGs are associated with the onset and progression of BLCA. A FRGs signature offers a viable alternative to predict BLCA, and these FRGs show a prospective research area for BLCA targeted treatment in the future.