bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychological Distress Associated With Suicidal Ideation Among Glaucoma Patients Attending at Tertiary Eye Care Clinic, Gondar, Ethiopia
Authors: Andualem Fantahun , Ali Dawed , Tinsae Techilo , Nakie Girum , Gedef Getachew Muluye , Demilew Demeke , Begashaw Tesfaye Derbie , Tegegn Lidiya Fasil , Seid Jemal
Published: November 2024

Introduction

Suicide is defined as the deliberate taking of one's own life with either implicit or explicit proof; however, it can also refer to the contemplation or actualization of suicide. Suicide is a mental illness with several contributing factors. It is frequently linked to sex, age, health problems, substance misuse, and traumatic life experiences.

Objective

The purpose of this study was to evaluate the prevalence of suicide thought and attempts among glaucoma patients and its contributing factors in Gondar, Ethiopia, 2022.

Methods

An observational cross-sectional study was conducted on 422 glaucoma patients at the Tertiary Eye Care Clinic, University of Gondar Comprehensive and Specialized Hospital. Suicidal ideation and attempts were assessed using the suicidality module of the World Mental Health Survey Initiative version of the World Health Organization's Composite International Diagnostic Interview. Bivariate and multivariate logistic regressions were conducted to identify factors associated with suicidal ideation and attempts. The variables with a p-value less than 0.05 and a 95% CI were considered statistically significant.

Results

The overall prevalence of suicidal ideation and attempt was 6.4% with a 95% CI of 4.3–9.2% and 2.4% with a 95% CI of 1.1–4.3%, respectively. In multivariate analysis, severe psychological distress, moderate psychological distress, mild psychological distress, and current substance use were identified as risk factors for suicidal ideation, whereas living alone, co-morbid chronic medical disease, and ever-present substance use were identified as risk factors for suicidal attempts.

Conclusion

Based on this study finding, the prevalence of suicidal ideation and attempts was high among glaucoma patients. This study may provide further information to pay much attention to the physical health care of patients with glaucoma. More representative samples, or rather, a cross-sectional study design, should be used in future studies aiming for more precise data.
Nursing Students, Faculty, and Preceptors Perception of Effective Characteristics of Clinical Instructor: A Cross-Sectional Study
Authors: Buanz Shmayil F. , Alsenayien Abrar Y. , Altharman Hanin A. , Alnaqi Rawan I. , Llaguno Maria Blesilda B. , Mousa Ola , Siraj Rayan A.
Published: November 2024

Background

Nursing instructors play an important role in improving the clinical experience of nursing students. Despite this, little is known about the characteristics of effective clinical instructors.

Objective

Identifying the perceptions of nursing students, faculty, and preceptors of effective clinical instructors.

Method

A descriptive cross-sectional study was conducted using a convenience sample of nursing students, faculty, and preceptors from different nursing departments. Participants were invited to respond to sociodemographic and Nursing Clinical Teacher Effectiveness Inventory questionnaires from April 2022 to September 2022. The data were analyzed using descriptive and inferential statistics using SPSS.

Result

A total of 715 participants responded to the survey, of whom 510 were students. Students valued interpersonal relations (5.57 ± 1.261) as the most important clinical instructor characteristic, while nursing competence was perceived as the least important (5.51 ± 1.298). Faculty scored the highest mean in the evaluation subscale (6.21 ± 1.170) and the lowest in nursing competence (6.07 ± 1.221). Preceptors scored the highest mean in the evaluation subscale (5.98 ± 0.904) and the lowest in personality (5.80 ± 0.928). One-way ANOVA showed significant mean differences between the perceptions of nursing students, faculty, and preceptors in personality ( M: 5.54 vs. 6.10 vs. 5.80, respectively; p < .001), evaluation ( M: 5.56 vs. 6.21 vs. 5.98; p < .001), teaching ability ( M: 5.57 vs. 6.12 vs. 5.86; p < .001), nursing competence ( M: 5.51 vs. 6.12 vs. 5.86; p < .001), and interpersonal relationship ( M: 5.57 vs. 6.17 vs. 5.88; p < .001). There were significant mean differences in students’ perceptions across academic levels.

Conclusion

Students, faculty, and preceptors perceived effective clinical instructors’ characteristics differently. Therefore, nursing schools should establish and promote a program to develop and promote unified, effective clinical teaching characteristics.
A Survey Study on the Factors Affecting Breastfeeding Self-Efficacy Among Postpartum Women in Mother–Infant Separation Wards
Authors: Si Cheng Cheng , Mao Aimei
Published: November 2024

Background

Self-efficacy serves as a crucial predictor for successful breastfeeding. The standard practice in maternal wards is mother–baby rooming-in, which is believed to enhance breastfeeding rates post-delivery. However, in certain maternal wards, mother–baby separation continues to occur due to diverse factors.

Objectives

The objective of this study is to examine the self-efficacy levels of mothers in mother–infant separation wards and identify the factors that influence their self-efficacy.

Methods

A cross-sectional study was undertaken in 2022 at a hospital in Macau, involving 290 postpartum women in mother–infant separation wards. A self-designed questionnaire encompassing demographic details and breastfeeding information was utilized. Additionally, the Chinese version of the Breastfeeding Self-Efficacy Scale (BSES) and the Social Support Scale (SSRS) were employed. SPSS26.0 software was used to analyze the data. p < .05 indicated statistically significant differences.

Results

The average breastfeeding self-efficacy score among the women was 96.03 ± 23.07, which accounted for 64% of the total score. The factors influencing breastfeeding self-efficacy were ranked based on their impact power as follows: previous experience of breastfeeding, intended length of breastfeeding, employment status, and the number of breastfeeding sessions during hospitalization after childbirth ( p < .05). These four factors collectively explained 34.7% (R2 = 0.347) of the variations in breastfeeding self-efficacy scores. A weak but positive correlation was observed between postpartum women's breastfeeding self-efficacy and social support for the mothers ( r = .341, p < .001).

Conclusion

The breastfeeding self-efficacy scores of postpartum women were found to be at a moderate level. Mother–infant separation during the postpartum period has an impact on breastfeeding self-efficacy, but the impact can be managed. When developing programs to enhance postpartum mothers’ breastfeeding self-efficacy, it is important to consider their individual and social circumstances, as well as the advantages and disadvantages associated with mother–infant separation during the postpartum period.
Factors Effective in Lowering Professional Commitment in Nursing and Strategies to Address Them: A Scoping Review
Authors: Nabi Foodani Mahdi , Abbasi Dolatabadi Zahra , Goudarzian Amir Hossein , Mosazadeh Hasan , Poortaghi Sarieh
Published: November 2024

Objectives

This study explores the factors leading to decreased professional commitment among nurses and proposes actionable solutions to mitigate the challenges posed by this phenomenon in nursing.

Methods

This research was conducted by employing the scoping review methodology. To this end, the relevant studies were obtained by two researchers independently searching over Scopus, Medline (via PubMed), Proquest, SID, Magiran, and Web of Science databases. The extracted data from the primary studies were organized into a table, including author names, publication year, study population, study objectives, study methodology, and key findings.

Results

Based on the primary research question, seven main themes contributing to the decline in professional commitment to nursing were determined as follows: professional and organizational challenges, human relations, personal wellbeing and coping, work–life balance and success, organizational culture, the nature of the nursing profession and beliefs, human emotions, values, and ethics. Also, the secondary question of the research was responded to by identifying four main themes: (1) empowering nurses, (2) nursing leadership and support, (3) safety concerns and interactions with patients, and (4) welfare facilities.

Conclusion

The findings of this study highlight the necessity of implementing nurse empowerment programs and providing financial and moral support from the organization and nursing leaders to enhance professional commitment to nursing.
Keller and Interphalangeal Joint Resection Arthroplasties for Chronic Noncomplicated Diabetic Ulcers of the Hallux: A Systematic Review and Meta-analysis
Authors: Yammine Kaissar , Mouawad Joseph , Honeine Mohammad Omar , Assi Chahine
Published: November 2024

Background:

Surgery is often needed for resistant plantar diabetic foot ulcers (DFUs) of the big toe. For noninfected ulcers, 2 types of surgery are available: the Keller and the hallux interphalangeal joint arthroplasty (HIPJ-A) procedures. Yet, no evidence synthesis on the outcomes of these procedures has been conducted; thus, this systematic review is an attempt to fill this gap.

Methods:

Only studies reporting the results of Keller (or its variants) and HIPJ-A (or its variants) procedures for noncomplicated ulcers (Texas 1A/2A, or Wagner I/II) were included. Ulcers located beneath the metatarsal head were excluded. Ultimately, 11 studies were selected for inclusion and were analyzed. The primary outcome was defined as the ulcer healing frequency. The secondary outcomes were mean healing time, ulcer recurrence frequency, ulcer transfer frequency, postoperative infection rate, and revision surgery rate.

Results:

The overall (combined techniques) weighted healing rate was 94% with a mean healing time of 3.1 ± 0.4 weeks. The ulcer recurrence frequency was 6%, the ulcer transfer frequency 4.5%, the postoperative infection rate 18%, and the revision surgery rate 3.8%. No significant differences were found between both techniques. When compared to standard of care, the odds ratio of ulcer healing frequency was 27.1 (95% CI 1.442-508.174, P = .01) in favor of the Keller arthroplasty with a faster healing time ( P = .02).

Conclusion:

Both surgical offloading procedures are highly effective in treating chronic noncomplicated DFU of the plantar aspect of the hallux along with low complication frequencies. There is a need to fine-tune the indication in relation to the location of the plantar wound with future comparative controlled research studies with far more patients than we could include in this meta-analysis.
Criteria for Identifying Candidates for Systemic Psoriasis Treatment in the Real World: Application of the International Psoriasis Council Guidelines in Patients in North America
Authors: Strober Bruce , Zhong Yichen , Sima Adam , Beeghly Alicia , Eckmann Thomas , Balagula Eugene , Zhuo Joe , Lebwohl Mark
Published: November 2024

Background

The International Psoriasis Council (IPC) updated the classification of psoriasis severity to guide clinical decision-making. According to IPC guidelines, patients are considered candidates for systemic therapy when body surface area (BSA) is >10%, when lesions affect special body areas (ie, face, palms, soles, genitals, scalp, or nails), or when topical therapy fails to control symptoms.

Objective

To evaluate patient candidacy for systemic therapy in real-world settings, according to disease severity criteria.

Methods

This cross-sectional study included systemic treatment-naive patients from the CorEvitas Psoriasis Registry who initiated systemic treatment at Registry visits between April 2015 and April 2023. Based on IPC criteria, systemic therapy candidates were identified, and data on demographics and clinical characteristics, including disease severity indicators (ie, BSA and Psoriasis Area Severity Index [PASI] scores) and patient-reported outcome measures, were collected and descriptively summarized.

Results

The analysis included 2739 systemic therapy initiators with plaque psoriasis, of whom 82.7% met IPC criteria for systemic therapy. Of the 2265 systemic therapy candidates, 56.2% had a BSA >10%, 53.2% had a history of psoriasis affecting special areas, and 55.2% had prior but not current use of topical therapy. Notably, 71.0% of candidates for systemic therapy had PASI scores ≤12.

Conclusion

In this large real-world study, most patients with psoriasis who initiated systemic therapy met the IPC disease severity criteria to do so. Disease severity categorization based on PASI scores and BSA percentage alone may not adequately capture all patients who might be candidates for systemic psoriasis treatment.

Clinicaltrials.gov

NCT02707341.
Review of electrokinetic flows and their applications in BioMEMS sensors
Authors: Bhatt Geeta , Bhattacharya Shantanu , Vashist Amit
Published: November 2024

BioMEMS integrates various interdisciplinary research domains to facilitate biological detection of analytes on electromechanically integrated microchips. It inherently utilizes electrical supplies to the system to serve the detection in many ways except colorimetric detection. In the context of microchip-based devices, the electric pulses generally serve one of the two primary purposes, either as low-level excitation signal or as a source of analyte manipulation in some manner. Among these effects, the study of the effect of electric pulses on the solution flow causing analyte manipulation is termed as electrokinetics. Depending on the kind of applied signal, there can be alternating current (AC) or direct current (DC) electrokinetics. These effects can be integrated into the detection system through various means. In this context, this review article discusses in detail the utility of integrating electrokinetics in detection, the associated parameters, the various electrokinetics effects, and their applications in biological detection. Some important applications chosen for discussion are particle pre-concentration, particle separation, particle rotation, and gene transformation.
A Case of Tubercular Pleural Effusion in a Child Following Erythema Nodosum
Authors: Verma Shalini , Kapoor Sakshi , Srivastava Geetika
Published: November 2024

Erythema nodosum (EN), a form of septal panniculitis, is rare in pediatric age group. It can be primary/idiopathic as well as secondary due to various conditions such as tuberculosis, streptococcal infections, autoimmune disorders, drugs, and inflammatory bowel diseases. The association of EN with latent tuberculosis has been widely reported in the adult population but literature is scarce on the association of EN with tuberculosis in the pediatric age group.

Here we present a case of a child who presented with pleural effusion of tubercular origin with a recent history of EN. The patient was also evaluated for the other causes of EN and responded well to the antitubercular treatment.
Beyond static measurements: dynamic frailty improves survival prediction in multiple myeloma
Authors: Smits Febe , Groen Kaz , Levin Mark-David , Stege Claudia A. M. , van Kampen Roel , van der Spek Ellen , Bilgin Yavuz M. , Thielen Noortje , Nijhof Inger , Ludwig Inge , de Waal Esther G. M. , Sandberg Yorick , Kentos Alain , Timmers Gert-Jan , Regelink Josien C. , Westerman Matthijs , de Heer Koen , Vekemans Marie-Christiane , Durdu-Rayman Nazik , de Graauw Nicole C. H. P. , Seefat Maarten R. , van de Donk Niels W. C. J. , Ypma Paula F. , Nasserinejad Kazem , Zweegman Sonja
Published: November 2024

The level of frailty, according to the International Myeloma Working Group frailty index, is highly dynamic during antimyeloma treatment. Dynamic frailty assessment improved the prediction of survival and early mortality compared with the prognostic value of static frailty level at baseline.
TRPV4 activation by core body temperature has multimodal functions in the central nervous system
Authors: Shibasaki Koji
Published: November 2024

Brain temperature is strictly regulated by various endogenous mechanisms and significantly contributes to brain function in homeothermic animals, making it an important factor for health. Thermosensitive transient receptor potential (TRP) channels convert temperature information into electrical signals through cation influx. In particular, TRPV4 is involved in the regulation of brain function. TRPV4, constitutively active in neurons through its activation by brain temperature, increases neuronal firing. TRPV4KO mice have electroencephalogram abnormalities, resulting in depression-like and social behavioral abnormalities. This basic function of TRPV4, as a translator of brain temperature information, has been implicated in several diseases, including epilepsy and stress-induced depression. In addition to its neuronal functions, TRPV4 has many key functions in glia and vasculature that depend on brain temperature and contribute to brain activity. In this review, I summarize the importance of TRPV4 activities in relation to brain temperature and focus on how hyperthermia-induced TRPV4 dysfunction exacerbates brain diseases.
Mitochondrial dysfunction and impaired DNA damage repair through PICT1 dysregulation in alveolar type II cells in emphysema
Authors: Simborio Hannah , Hayek Hassan , Kosmider Beata , Elrod John W. , Bolla Sudhir , Marchetti Nathaniel , Criner Gerard J. , Bahmed Karim
Published: November 2024

Background

Alveolar type II (ATII) cells have a stem cell potential in the adult lung and repair the epithelium after injury induced by harmful factors. Their damage contributes to emphysema development, characterized by alveolar wall destruction. Cigarette smoke is the main risk factor for this disease development.

Methods

ATII cells were obtained from control non-smoker and smoker organ donors and emphysema patients. Isolated cells were used to study the role of PICT1 in this disease. Also, a cigarette smoke-induced murine model of emphysema was applied to define its function in disease progression further.

Results

Decreased PICT1 expression was observed in human and murine ATII cells in emphysema. PICT1 was immunoprecipitated, followed by mass spectrometry analysis. We identified MRE11, which is involved in DNA damage repair, as its novel interactor. PICT1 and MRE11 protein levels were decreased in ATII cells in this disease. Moreover, cells with PICT1 deletion were exposed to cigarette smoke extract. This treatment induced cellular and mitochondrial ROS, cell cycle arrest, nuclear and mitochondrial DNA damage, decreased mitochondrial respiration, and impaired DNA damage repair.

Conclusions

This study indicates that PICT1 dysfunction can negatively affect genome stability and mitochondrial activity in ATII cells, contributing to emphysema development. Targeting PICT1 can lead to novel therapeutic approaches for this disease.
The immune regulatory role of lymphangiogenesis in kidney disease
Authors: Lu Xiangheng , Ma Kuai , Ren Junyi , Peng Haoyu , Wang Jia , Wang Xiaoxiao , Nasser Moussa Ide , Liu Chi
Published: November 2024

The renal lymphatic system is critical for maintaining kidney homeostasis and regulating the immune response inside the kidney. In various kidney pathological situations, the renal lymphatic network experiences lymphangiogenesis, which is defined as the creation of new lymphatic vessels. Kidney lymphangiogenesis controls immunological response inside the kidney by controlling lymphatic flow, immune cell trafficking, and immune cell regulation. Ongoing study reveals lymphangiogenesis’s different architecture and functions in numerous tissues and organs. New research suggests that lymphangiogenesis in kidney disorders may regulate the renal immune response in various ways. The flexibility of lymphatic endothelial cells (LECs) improves the kidney’s immunological regulatory function of lymphangiogenesis. Furthermore, current research has shown disparate findings regarding its impact on distinct renal diseases, resulting in contradictory outcomes even within the same kidney condition. The fundamental causes of the various effects of lymphangiogenesis on renal disorders remain unknown. In this thorough review, we explore the dual impacts of renal lymphangiogenesis on several kidney pathologies, with a particular emphasis on existing empirical data and new developments in understanding its immunological regulatory function in kidney disease. An improved understanding of the immunological regulatory function of lymphangiogenesis in kidney diseases might help design novel medicines targeting lymphatics to treat kidney pathologies.
Association between the heaviness of smoking index (HSI) and quit attempts and quit intentions among cigarette smokers in eight African countries
Authors: Jena Pratap Kumar , Okoye Pamela Chekwube , Patel Arpita , Satpathy Nancy , Kamsa-ard Supot , Mohapatra Debasish , Mangoti Shilpa , Nyirenda Esther , Desta Getahun Bahiru , Justin Elikana Kulwa
Published: November 2024

Introduction

The increasing smoking population in Africa necessitates intensified tobacco cessation services. Assessing nicotine dependence with tools such as the heaviness of smoking index (HSI) aids in cessation efforts. This study evaluated the association between HSI and quit attempts and quit intentions among African cigarette smokers.

Methods

Global Adult Tobacco Survey (GATS) data from eight African countries collected between 2011 and 2018 were analysed. The time to first smoke (TTFS) and number of cigarettes per day (CPD) were used to estimate the HSI score and dependence level. The association between HSI dependence level and quit attempts and quit intentions was evaluated using likelihood ratios (LR).

Results

Among 2,399 daily cigarette users, 1,618 (67.5%) were exclusive cigarette users. The average and median CPDs were 8.27 ± 8.3 and 5 (IQR: 2–18), respectively, with Ethiopia having the highest mean CPD (11.6). In Ethiopia, 51.5% of exclusive and 42% of nonexclusive users had low dependence (HSI < 2), whereas 43.9% and 31.3% of other African countries had low dependence. The association between low dependence and quit attempts was significant only for exclusive cigarette smokers in Ethiopia, with LR of 1.45 (95% CI: 1.08–1.93). The association between low dependence and quit intentions was significant in Ethiopia for both exclusive (LR = 1.42) and nonexclusive (LR = 1.53) users. None of the LR estimates were > 10 or < 0.1.

Conclusion

The association between low dependence (HSI < 2) and quit behaviour was limited in African settings, highlighting the complex interplay between usage patterns, dependence assessment, and quit behaviour. A contextual tool for assessing nicotine dependence tailored to African settings is warranted for effective smoking cessation.
Pneumonitis after normofractionated radioimmunotherapy: a method for dosimetric evaluation
Authors: Kraus Kim Melanie , Bauer Caroline , Steinhelfer Lisa , Feuerecker Benedikt , Martins Juliana Cristina , Fischer Julius Clemens , Borm Kai Joachim , Peeken Jan Caspar , Bernhardt Denise , Combs Stephanie Elisabeth
Published: November 2024

Background

Post-Therapy-Pneumonitis (PTP) is a critical side effect of both, thoracic radio(chemo)therapy (R(C)T) and immune checkpoint inhibition (ICI). However, disease characteristics and patient-specific risk factors of PTP after combined R(C)T + ICI are less understood. Given that RT-triggered PTP is strongly dependent on the volume and dose of RT [1], driven by inflammatory mechanisms, we hypothesize that combination therapy of R(C)T with ICI influences the dose-volume-effect correlation for PTP. This study focuses on the development of a method for evaluation of alterations of dosimetric parameters for PTP after R(C)T with and without ICI.

Methods and materials

PTP volumes were delineated on the follow-up diagnostic Computed Tomography (CT) and deformably matched to the planning CT for patients with PTP after thoracic R(C)T + ICI or R(C)T. Dose data was converted to 2-Gy equivalent doses (EQD2) and dosimetrically analyzed. Dosimetric and volumetric parameters of the segmented PTP volumes were analyzed. The method was exemplarily tested on an internal patient cohort including 90 patients having received thoracic R(C)T + ICI (39) and R(C)T (51). Thirtytwo patients with PTP were identified for further analysis. Additional data on previous chemotherapy, RT, smoking status and pulmonary co-morbidity were conducted. A matched pair analysis with regard to planning target volumes (PTV) was conducted for curative intended (definitive) and palliative patient cohorts individually.

Results

The presented method was able to quantify and compare the dosimetric parameters of PTP for the different therapies. For our study group, no significant differences between R(C)T + ICI and R(C)T only was observed. However, the dosimetric analysis revealed large volumetric fractions (55%) of the PTP volumes to be located outside of high dose (EQD2 < 40 Gy) regions for R(C)T + ICI. There was a non-significant trend towards increased area under the curve of the dose volume histogram (AUC) values for R(C)T + ICI compared to R(C)T only (3743.6 Gy∙% vs. 2848.8 Gy∙%; p-value = 0.171). In contrast to the data for the palliative intended treatment group, for definitive R(C)T + ICI, data tended towards increased volumes with higher doses.

Conclusions

The proposed method was capable to quantify dosimetric differences in the dose-volume-effect relationship of PTP for patients with R(C)T + ICI and patients with R(C)T only. In this exploratory analysis, no significant dosimetric differences within PTP volumes for the different groups could be observed. However, our observations suggest, that for safe application of thoracic R(C)T + ICI, further careful investigation of dosimetric prescription and analysis concepts with larger and conformer study groups is recommendable.
Gastrodin attenuates diabetic cardiomyopathy characterized by myocardial fibrosis by inhibiting the KLK8-PAR1 signaling axis
Authors: Zhang MingShan , Zhang YuFei , He JingGang , Wang XinRui , Wang YinYin , Li LinYan , Tao Ling , Zhang Min , Shen Xiangchun
Published: November 2024

Background

Diabetic cardiomyopathy (DCM), characterized by myocardial fibrosis, is a major cause of mortality and morbidity in diabetic patients; the inhibition of cardiac fibrosis is a fundamental strategy for treating DCM. Gastrodin (GAS), a compound extracted from Gastrodia elata protects against DCM, but the molecular mechanism underlying its antifibrotic effect has not been elucidated.

Methods

In vivo, the effects of GAS were investigated using C57BL/6 mice with DCM, which was induced by administering a high-sugar, high-fat (HSF) diet and streptozotocin (STZ). We assessed the cardiac function in these mice and detected histopathological changes in their hearts and the degree of cardiac fibrosis. In vitro, neonatal rat cardiac fibroblasts (CFs) were transformed into myofibroblasts by exposing them to high glucose combined with high palmitic acid (HG-PA), and CFs were induced by pEX-1 (pGCMV/MCS/EGFP/Neo) plasmid-mediated overexpression of KLK8, which contains the rat KLK8 gene. The KLK8 siRNA was knocked down to study the effects of GAS on CF differentiation, collagen synthesis, and cell migration by specific mechanisms of action of GAS.

Results

GAS attenuated pathological changes in the hearts of DCM mice, rescued impaired cardiac function, and attenuated cardiac fibrosis. Additionally, the results of molecular docking analysis showed that GAS binds to kinin-releasing enzyme-related peptidase 8 (KLK8) to inhibit the increase in protease-activated receptor-1 (PAR-1), thus attenuating myocardial fibrosis. Specifically, GAS attenuated the transformation of neonatal rat CFs to myofibroblasts exposed to HG-PA. Overexpressing KLK8 promoted CF differentiation, collagen synthesis, and cell migration, and KLK8 siRNA attenuated HG-PA-induced CF differentiation, collagen synthesis, and cell migration. Further studies revealed that a PAR-1 antagonist, but not a PAR-2 antagonist, could attenuate CF differentiation, collagen synthesis, and cell migration. Additionally, GAS inhibited KLK8 upregulation and PAR1 activation, thus blocking the differentiation, collagen synthesis, and cell migration of HG-PA-exposed CFs and triggering TGF-β1/Smad3 signaling.

Conclusion

GAS alleviated pathological changes in the hearts of DCM model mice induced by an HSF diet combined with STZ. KLK8 mediated HG-PA-induced differentiation, collagen synthesis, and the migration of CFs. GAS attenuated the differentiation, collagen synthesis, and migration of CFs by inhibiting the KLK8-PAR1 signaling axis, a process in which TGF-β1 and Smad3 are involved.

Graphical Abstract
Associations between genetic variants of Toll-interacting proteins and interstitial lung diseases: a systematic review and meta-analysis
Authors: Li Xiaoyuan , Cui Beibei , Jiang Lili
Published: November 2024

Background

Genetic polymorphisms in Toll-interacting protein (TOLLIP) have been documented in relation to clinical manifestations of interstitial lung disease (ILD). Nevertheless, the findings across studies present inconsistencies. The present meta-analysis endeavors to elucidate the nexus between genetic variations in TOLLIP and the onset and prognosis of interstitial lung disease (ILD), with the overarching aim of providing insight into the pathophysiological underpinnings of ILD.

Method

This systematic review was registered in PROSPERO. The OVID MEDLINE, OVID EMBASE, and Web of Science electronic databases were searched.

Results

Fourteen studies with a total of 4821 cases and 9765 controls were examined. The final TOLLIP variants to be included in this meta-analysis were rs5743890, rs111521887, and rs3750920. There were significantly fewer TOLLIP rs5743890 minor allele C carriers among individuals with interstitial lung disease (ILD) than among those without this condition (11.42% vs. 18.92%). Conversely, patients with ILD exhibited higher frequencies of rs111521887 minor allele G carriers (28.92% vs. 22.44%) and rs3750920 minor allele T carriers (40.06% vs. 34.00%). A potential association between rs5743890_C and a reduced incidence of ILD was plausible (p = 0.04, OR = 0.72, 95% CI = 0.53–0.99). Furthermore, a stratified analysis revealed that rs5743890_C was significantly associated with a decreased risk of IPF (p = 0.004, OR = 0.62, 95% CI = 0.44–0.86). There was a significant correlation between susceptibility to ILD and rs111521887 G (p < 0.00001, OR = 1.48, 95% CI = 1.33–1.65) and rs3750920 T (p < 0.00001, OR = 1.34, 95% CI = 1.26–1.44). The survival of IPF patients was correlated with the TOLLIP rs5743890 SNP, and patients with the rs5743890_C genotype had worse survival (p = 0.02, HR = 1.59, 95% CI = 1.07–2.36).

Conclusion

This study showed that rs5743890_C was associated with a lower incidence of ILD and a worse survival rate in patients with IPF. Rs111521887_G and rs3750920_T were found to be associated with an elevated risk of ILD incidence, while no significant association was observed with ILD prognosis. Furthermore, studies are warranted to validate our results and assess the effects of TOLLIP genetic variants on ILD.
AKAP6 controls NFATc4 activity for BDNF-mediated neuroprotection
Authors: Mackiewicz Joanna , Tomczak Julia , Lisek Malwina , Guo Feng , Boczek Tomasz
Published: November 2024

Brain-derived neurotrophic factor (BDNF) is known for its potent prosurvival effect. Despite successfully replicating this effect in various clinical and pre-clinical models, the complete characterization of the molecular mechanisms underlying its neuroprotective action remains incomplete. Emerging research suggests a vital role for A-kinase anchoring proteins (AKAPs) as central nodal points orchestrating BDNF-dependent signaling. Among the over 50 identified AKAPs, AKAP6 has recently gained special attention due to its involvement in the neurotrophin-mediated survival of injured retinal ganglion cells (RGCs). However, the mechanisms by which AKAP6 responds to pro-survival BDNF signaling remain unknown. In this study, we shown that AKAP6 plays a crucial role in regulating BDNF-mediated NFAT transcriptional activity in neuronal survival by anchoring protein phosphatase calcineurin (CaN) and nuclear factor of activated T cells (NFATc4). Furthermore, we demonstrate that disrupting the anchoring of CaN diminishes the pro-survival effect of BDNF. Lastly, through experiments with NFATc4−/− mice, we provide evidence that NFATc4 acts downstream to BDNF’s neuroprotection in vivo. These findings could offer valuable insights for developing neuroprotective strategies aimed at preserving injured neurons from degeneration and promoting their regeneration.
Intravitreal injection of the Galectin-3 inhibitor TD139 provides neuroprotection in a rat model of ocular hypertensive glaucoma
Authors: Rombaut Anne , Brautaset Rune , Williams Pete A. , Tribble James R.
Published: November 2024

Neuroinflammation is a significant contributor to the pathology of glaucoma. Targeting key-mediators in this process is a realistic option to slow disease progression. Galectin-3 is a β-galactoside binding lectin that has been associated with inflammation in both systemic and central nervous system diseases. Elevated Galectin-3 has recently been detected in multiple animal models of glaucoma and inhibiting Galectin-3 using an intravitreal injection of TD139 (a Galectin-3 small molecule inhibitor) is neuroprotective. We queried whether this neuroprotective effect was translatable to another animal model and species. TD139 was intravitreally injected, in a rat ocular hypertensive model of glaucoma, 3 days after the induction of ocular hypertension (at peak intraocular pressure). Retinal ganglion cell survival and glial morphological markers were quantified. The degeneration of retinal ganglion cells was prevented by TD139 injection, but gross glial markers remained unaffected. These data confirm that the intravitreal injection of TD139 is neuroprotective in a rat ocular hypertensive model of glaucoma, while suggesting that the inhibition of Galectin-3 is not sufficient to alter the gross inflammatory outcome.
Experience of patent ductus arteriosus ligation during extracorporeal membrane oxygenation treatment in newborns with severe respiratory failure due to persistent pulmonary hypertension: a single-center retrospective study
Authors: Zhang Qi-Liang , Liu Yi-Nan , Zeng Ya-Ting , Zheng Yi-Rong , Chen Qiang
Published: November 2024

Background

The aim of this study is to summarize our center’s experience with patent ductus arteriosus (PDA) ligation during extracorporeal membrane oxygenation (ECMO) treatment in newborns with severe respiratory failure due to persistent pulmonary hypertension of the newborn (PPHN).

Methods

We retrospectively collected and analyzed clinical data from five newborns with severe respiratory failure due to PPHN who underwent PDA ligation during ECMO treatment at our hospital between January 2021 and August 2023.

Results

All five patients had large PDAs, measuring 10 mm, 6 mm, 6 mm, 7 mm, and 6 mm, respectively. Significant left-to-right shunting through the PDA was observed after 29 h, 14 h, 3 h, 7 h, and 5 h of ECMO treatment, respectively, at which point successful PDA ligation was performed. The surgical durations were 52 min, 45 min, 55 min, 50 min, and 40 min, respectively. Post-ligation, blood lactate levels significantly decreased compared to preoperative values. Four patients were successfully weaned off ECMO, with ECMO support durations of 64 h, 92 h, 70 h, and 87 h, respectively. After ECMO removal, mechanical ventilation was discontinued after 5.2 days, 7.2 days, 9.5 days, and 5.5 days, respectively. None of the four surviving patients experienced complications such as residual shunting, bleeding, chylothorax, neurologic injury, pneumothorax, poor wound healing, or sepsis.

Conclusion

During ECMO treatment for PPHN in newborns with large PDAs, the direction of blood flow through the PDA should be closely monitored. PDA ligation is a feasible and reasonable intervention when pulmonary artery pressure decreases and left-to-right shunting through the PDA becomes evident.
Deprescribing anticholinergics to preserve brain health: reducing the risk of dementia through deprescribing (R2D2): study protocol for a randomized clinical trial
Authors: Campbell Noll L. , Holden Richard J. , Gao Sujuan , Unverzagt Frederick W. , Lane Kathleen A. , Carter Allie , Harrington Addison B. , Manoharan Sneha , Manoharan Neha , Rosenthal Danielle L. , Pitts Christopher , Pelkey Kathryn , Papineau Emily , Lauck David M. , Keshk Noha , Alamer Khalid , Khalil Hussein , Boustani Malaz A.
Published: November 2024

Background

Older adults commonly experience chronic medical conditions and are at risk of cognitive impairment as a result of age, chronic comorbidity, and medications prescribed to manage multiple chronic conditions. Anticholinergic medications are common treatments for chronic conditions and have been repeatedly associated with poor cognitive outcomes, including delirium and dementia, in epidemiologic studies. However, no study has definitively evaluated the causal relationship between anticholinergics and cognition in a randomized controlled trial design. Utilizing our prior experience in deprescribing anticholinergic medications in various clinical environments, we designed an outpatient deprescribing intervention to prospectively test the potential causal relationship between anticholinergics and cognition in primary care older adults.

Methods

This cluster randomized clinical trial will be conducted to evaluate the impact of an anticholinergic deprescribing intervention compared to usual care on outcomes of cognition and safety in primary care older adults. Participants will include those aged 65 years and over, receiving primary care in the greater Indianapolis area, using a strong anticholinergic within the last 2 weeks or with evidence of high-risk exposure in the past year. Those excluded will have a diagnosis of Alzheimer’s disease or related dementia, or serious mental illness. The trial plans to enroll 344 participants who will be cluster-randomized at the level of primary care physician to avoid contamination. Participants will complete outcome assessments every 6 months up to 2 years by blinded outcome assessors. The primary outcome of the study is a composite measure of cognition that includes domains assessing executive cognitive function, language, and memory. Secondary outcomes include patient-reported measures of pain intensity, depression, anxiety, sleep disturbance, and health-related quality of life.

Discussion

The R2D2 trial will be the largest and longest prospective randomized trial testing the impact of an anticholinergic-specific deprescribing intervention on cognition in primary care older adults. Results could influence deprescribing methodology and provide new insight on the relationship between anticholinergics and cognition.

Trial registration

ClinicalTrials.gov NCT04270474. Registered on February 17, 2020.
Complete genome sequence of Bacillus pumilus NWMCC0302, a strain for degrading bovine blood
Authors: Xiang Jun , Liao Qingyan , Zeng Songyu , Zhou Wei , Ma Zhongren , Ding Gongtao , Zhou Xueyan
Published: November 2024

Background

Directly discharging livestock and poultry slaughter blood without proper treatment can cause severe ecological damage. Exploring the use of microorganisms to break down waste blood into smaller molecules such as peptides and amino acids, as well as investigating the possibility of transforming these small molecules into water-soluble fertilizers containing amino acids, holds significant research value in the comprehensive utilization of livestock and poultry blood.

Results

In this study, a single strain of Bacillus pumilus NWMCC0302, which has effectively degraded bovine blood, was isolated from abattoir blood sludge using casein agar plates and Columbia blood agar plates. The degradation test was carried out using bovine raw blood as a nitrogen source in the medium, and the results showed that the strain degraded 53.83% of bovine blood under optimal degradation conditions. The whole genome sequencing of Bacillus pumilus NWMCC0302 was conducted using the second-generation DNBSEQ platform and the third-generation PacBio platform, employing high-throughput sequencing technology. The size of the strain's entire genome was determined to be 3 868 814 bp with a G-C content of 41.63%. The total gene length accounted for 88.98% of the genome length at 3 442 341 bp and encoded 4 113 genes. The strain contained 79 tRNAs, 24 rRNAs, 7 sRNAs, and 296 repetitive sequences. The gene data obtained from sequencing were also functionally annotated using the COG, KEGG, and VFDB databases. In the COG database, 310 genes were involved in amino acid transport and metabolism, including 10 catabolic proteins related to COGs. In the KEGG database, were 201 genes involved in amino acid metabolism pathways, including 8 genes in nitrogen metabolism pathways and 2 genes in oxidative pathways. The VFDB database contains two lysostaphin genes and one serine protease-hydrolyzed ClpP gene.

Conclusions

In summary, Bacillus pumilus NWMCC0302 was screened for its efficient ability to degrade bovine blood. Additionally, the genetic information of Bacillus pumilus NWMCC0302 was revealed at the genetic level, providing a feasible experimental method for applying this strain to the degradation of blood from slaughtered livestock and poultry. Moreover, it is a potential functional strain for producing amino acid-containing water-soluble fertilisers.
Exosome crosstalk between cancer stem cells and tumor microenvironment: cancer progression and therapeutic strategies
Authors: Li Qi , He Guangpeng , Yu Yifan , Li Xinyu , Peng Xueqiang , Yang Liang
Published: November 2024

Cancer stem cells (CSCs) represent a small yet pivotal subset of tumor cells endowed with self-renewal capabilities. These cells are intricately linked to tumor progression and are central to drug resistance, metastasis, and recurrence. The tumor microenvironment (TME) encompasses the cancer cells and their surrounding milieu, including immune and inflammatory cells, cancer-associated fibroblasts, adjacent stromal tissues, tumor vasculature, and a variety of cytokines and chemokines. Within the TME, cells such as immune and inflammatory cells, endothelial cells, adipocytes, and fibroblasts release growth factors, cytokines, chemokines, and exosomes, which can either sustain or disrupt CSCs, thereby influencing tumor progression. Conversely, CSCs can also secrete cytokines, chemokines, and exosomes, affecting various components of the TME. Exosomes, a subset of extracellular vesicles (EVs), carry a complex cargo of nucleic acids, proteins, and lipids, playing a crucial role in the communication between CSCs and the TME. This review primarily focuses on the impact of exosomes secreted by CSCs (CSC-exo) on tumor progression, including their roles in maintaining stemness, promoting angiogenesis, facilitating metastasis, inducing immune suppression, and contributing to drug resistance. Additionally, we discuss how exosomes secreted by different cells within the TME affect CSCs. Finally, we explore the potential of utilizing exosomes to mitigate the detrimental effects of CSCs or to target and eliminate them. A thorough understanding of the exosome-mediated crosstalk between CSCs and the TME could provide valuable insights for developing targeted therapies against CSCs.
SCAN: a nanopore-based, cost effective decision-supporting tool for mass screening of aneuploidies
Authors: Schack Anne Kristine , Garrido-Navas M. Carmen , Galevski David , Madjarov Gjorgji , Krych Lukasz
Published: November 2024

In developed countries, Newborn Screening (NBS) programs aim to detect treatable yet clinically silent disorders. The selection of disorders to be included in NBS considers severity, treatment availability, prevalence, and analysis cost. However, numerous genetic disorders remain excluded from routine testing due to high expenses and specialized equipment requirements. Here we present SCAN, a novel, non-invasive, and cost-effective decision-support tool utilizing nanopore sequencing for estimating proportions of chromosomes responsible for the most common aneuploidies. SCAN combines DNA enrichment (amplification), barcoding, nanopore sequencing, and machine learning predictive modeling. In a proof-of-concept study for Klinefelter Syndrome, SCAN achieved 100% sensitivity, specificity, and accuracy, becoming the world’s first IVD-certified genetic test utilising nanopore sequencing. Further model training shows promise in expanding this assay to detect other chromosomal aneuploidies included in the protocol.
Noninvasive biomarkers implicated in urea and TCA cycles for metabolic liver disease
Authors: Yang Guiyan , Wan Yu-Jui Yvonne
Published: November 2024

Bile acid (BA) and its receptor FXR play crucial roles in metabolism, and dysregulated BA synthesis regulated by hepatic and bacterial enzymes causes metabolic dysfunction-associated steatohepatitis (MASH) and hepatocellular carcinoma (HCC). Moreover, because ~ 75% of hepatic blood is from the gut, liver metabolism is influenced by intestinal bacteria and their metabolites. Thus, we used gut microbiota and metabolites from the urine and serum to uncover biomarkers for metabolic distress caused by Western diet (WD) intake, aging, and FXR inactivity. Hepatic transcriptomes were profiled to define liver phenotypes. There were 654 transcriptomes commonly altered by differential diet intake, ages, and FXR functional status, representing the signatures of liver dysfunction, and 76 of them were differentially expressed in healthy human livers and HCC. Machine learning approaches classified urine and serum metabolites for differential dietary intake and age difference. Additionally, the gut microbiota could predict FXR functional status. Furthermore, FXR was essential for differentiating dietary effects in colonizing age-related gut microbes. The integrated analysis established the relationships between the metabolites and gut microbiota correlated with hepatic transcripts commonly altered by diet, age, and FXR functionality. Remarkably, the changes in metabolites involved in the urea cycle, mitochondrial metabolism, and amino acid metabolism are associated with hepatic dysfunction (i.e. FXF deactivation). Taken together, noninvasive specimens and biomarkers are promising resources for identifying metabolic distress.