bluuebunny/crossref_metadata_2025 huggingface dataset:
Epithelial MAPK signaling directs endothelial NRF2 signaling and IL-8 secretion in a tri-culture model of the alveolar-microvascular interface following diesel exhaust particulate (DEP) exposure
Authors: Vitucci Eva C. M. , Simmons Alysha E. , Martin Elizabeth M. , McCullough Shaun D.
Published: March 2024

Background

Particulate matter 2.5 (PM2.5) deposition in the lung’s alveolar capillary region (ACR) is significantly associated with respiratory disease development, yet the molecular mechanisms are not completely understood. Adverse responses that promote respiratory disease development involve orchestrated, intercellular signaling between multiple cell types within the ACR. We investigated the molecular mechanisms elicited in response to PM2.5 deposition in the ACR, in an in vitro model that enables intercellular communication between multiple resident cell types of the ACR.

Methods

An in vitro, tri-culture model of the ACR, incorporating alveolar-like epithelial cells (NCI-H441), pulmonary fibroblasts (IMR90), and pulmonary microvascular endothelial cells (HULEC) was developed to investigate cell type-specific molecular responses to a PM2.5 exposure in an in-vivo-like model. This tri-culture in vitro model was termed the alveolar capillary region exposure (ACRE) model. Alveolar epithelial cells in the ACRE model were exposed to a suspension of diesel exhaust particulates (DEP) (20 µg/cm2) with an average diameter of 2.5 µm. Alveolar epithelial barrier formation, and transcriptional and protein expression alterations in the directly exposed alveolar epithelial and the underlying endothelial cells were investigated over a 24 h DEP exposure.

Results

Alveolar epithelial barrier formation was not perturbed by the 24 h DEP exposure. Despite no alteration in barrier formation, we demonstrate that alveolar epithelial DEP exposure induces transcriptional and protein changes in both the alveolar epithelial cells and the underlying microvascular endothelial cells. Specifically, we show that the underlying microvascular endothelial cells develop redox dysfunction and increase proinflammatory cytokine secretion. Furthermore, we demonstrate that alveolar epithelial MAPK signaling modulates the activation of NRF2 and IL-8 secretion in the underlying microvascular endothelial cells.

Conclusions

Endothelial redox dysfunction and increased proinflammatory cytokine secretion are two common events in respiratory disease development. These findings highlight new, cell-type specific roles of the alveolar epithelium and microvascular endothelium in the ACR in respiratory disease development following PM2.5 exposure. Ultimately, these data expand our current understanding of respiratory disease development following particle exposures and illustrate the utility of multicellular in vitro systems for investigating respiratory tract health.
Comparative effectiveness of implementation strategies for Accelerating Cervical Cancer Elimination through the integration of Screen-and-treat Services (ACCESS study): protocol for a cluster randomized hybrid type III trial in Nigeria
Authors: Olakunde Babayemi O. , Itanyi Ijeoma U. , Olawepo John O. , Liu Lin , Bembir Chinenye , Idemili-Aronu Ngozi , Lasebikan Nwamaka N. , Onyeka Tonia C. , Dim Cyril C. , Chigbu Chibuike O. , Ezeanolue Echezona E. , Aarons Gregory A.
Published: March 2024

Background

Despite the increased risk of cervical cancer (CC) among women living with HIV (WLHIV), CC screening and treatment (CCST) rates remain low in Africa. The integration of CCST services into established HIV programs in Africa can improve CC prevention and control. However, the paucity of evidence on effective implementation strategies (IS) has limited the success of integration in many countries. In this study, we seek to identify effective IS to enhance the integration of CCST services into existing HIV programs in Nigeria.

Methods

Our proposed study has formative and experimental activities across the four phases of the Exploration, Preparation, Implementation, and Sustainment (EPIS) framework. Through an implementation mapping conducted with stakeholders in the exploration phase, we identified a core package of IS (Core) and an enhanced package of IS (Core+) mostly selected from the Expert Recommendations for Implementing Change. In the preparation phase, we refined and tailored the Core and Core+ IS with the implementation resource teams for local appropriateness. In the implementation phase, we will conduct a cluster-randomized hybrid type III trial to assess the comparative effectiveness of Core versus Core+. HIV comprehensive treatment sites (k = 12) will be matched by region and randomized to Core or Core+ in the ratio of 1:1 stratified by region. In the sustainment phase, we will assess the sustainment of CCST at each site. The study outcomes will be assessed using RE-AIM: reach (screening rate), adoption (uptake of IS by study sites), IS fidelity (degree to which the IS occurred according to protocol), clinical intervention fidelity (delivery of CC screening, onsite treatment, and referral according to protocol), clinical effectiveness (posttreatment screen negative), and sustainment (continued integrated CCST service delivery). Additionally, we will descriptively explore potential mechanisms, including organizational readiness, implementation climate, CCST self-efficacy, and implementation intentions.

Discussion

The assessment of IS to increase CCST rates is consistent with the global plan of eliminating CC as a public health threat by 2030. Our study will identify a set of evidence-based IS for low-income settings to integrate evidence-based CCST interventions into routine HIV care in order to improve the health and life expectancy of WLHIV.

Trial registration

Prospectively registered on November 7, 2023, at ClinicalTrials.gov no. NCT06128304. https://classic.clinicaltrials.gov/ct2/show/study/NCT06128304
Temporary pacing following cardiac surgery – a reference guide for surgical teams
Authors: Waqanivavalagi Steve W F R
Published: March 2024

Temporary pacing wires are often used following cardiac surgery to optimise the heart rhythm. Although setting and checking temporary pacemakers is typically undertaken by anaesthetists, intensivists, and nursing staff who care for post-cardiac surgical patients, almost all patients with temporary pacing wires are transferred to the ward with the pacing wires left in situ, where surgical, often junior, staff become responsible for temporary pacing wire management. Thus, knowledge is required not only of temporary pacing wire indications, types, and positioning at surgery, but also of practical skills in performing a pacing check, setting the pacemaker, and troubleshooting common problems. The available literature targets clinicians well-versed in temporary pacing wire management. However, this paper provides a practical ‘how to’ for surgical staff managing temporary pacing wires in a non-critical care environment.
Methodological advances in patient-centered rare disease research: the UTHealth Houston Turner Syndrome Society of the United States research registry
Authors: Mansoorshahi Sara , Scurlock Cindy , Research Registry Scientific Advisory Board of the Tu , Prakash Siddharth K
Published: March 2024

Background

Many different clinical specialists provide care to patients with Turner syndrome (TS), who have highly variable clinical manifestations. Therefore, a national TS registry is essential to inform a cohesive approach to healthcare and research. In 2015, the Turner Syndrome Society of the United States (TSSUS) created the Turner Syndrome Research Registry (TSRR) to engage directly with community participants who voluntarily provide longitudinal data about their experiences with TS. TSRR projects are collaborative partnerships between people with TS, TSSUS, and researchers.

Results

To ensure that registry workflows conform to the data privacy choices of participants, TSSUS collaborated with UTHealth Houston in 2021 to create a new version of the TSRR that completely separates participant health data (stored at UTHealth) and personal identifiers (maintained at TSSUS). We developed an innovative Visual Basic (VB) script that, when embedded into Microsoft Outlook, redirects REDCap surveys through TSSUS to participants by matching registry IDs to participant email addresses. Additionally, the utilization of REDCap allows for portability of data as it is an open source platform.

Conclusion

In this report, we will highlight three recent changes that more closely align the TSRR with this mission: a unique and equal collaborative partnership between UTHealth and TSSUS, an open-source platform, REDCap, that ensures data portability and compatibility across institutions, and an innovative survey routing system that retains participant confidentiality without sacrificing REDCap survey distribution capabilities to connect researchers with thousands of participants.
The diagnostic accuracy of cardiac ultrasound for acute myocardial ischemia in the emergency department: a systematic review and meta-analysis
Authors: Zarama Virginia , Arango-Granados María Camila , Manzano-Nunez Ramiro , Sheppard James P. , Roberts Nia , Plüddemann Annette
Published: March 2024

Background

Chest pain is responsible for millions of visits to the emergency department (ED) annually. Cardiac ultrasound can detect ischemic changes, but varying accuracy estimates have been reported in previous studies. We synthetized the available evidence to yield more precise estimates of the accuracy of cardiac ultrasound for acute myocardial ischemia in patients with chest pain in the ED and to assess the effect of different clinical characteristics on test accuracy.

Methods

A systematic search for studies assessing the diagnostic accuracy of cardiac ultrasound for myocardial ischemia in the ED was conducted in MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, Web of Science, two trial registries and supplementary methods, from inception to December 6th, 2022. Prospective cohort, cross-sectional, case–control studies and randomized controlled trials (RCTs) that included data on diagnostic accuracy were included. Risk of bias was assessed with the QUADAS-2 tool and a bivariate hierarchical model was used for meta-analysis with paired Forest and SROC plots used to present the results. Subgroup analyses was conducted on clinically relevant factors.

Results

Twenty-nine studies were included, with 5043 patients. The overall summary sensitivity was 79.3% (95%CI 69.0–86.8%) and specificity was 87.3% (95%CI 79.9–92.2%), with substantial heterogeneity. Subgroup analyses showed increased sensitivity in studies where ultrasound was conducted at ED admission and increased specificity in studies that excluded patients with previous heart disease, when the target condition was acute coronary syndrome, or when final chart review was used as the reference standard. There was very low certainty in the results based on serious risk of bias and indirectness in most studies.

Conclusions

Cardiac ultrasound may have a potential role in the diagnostic pathway of myocardial ischemia in the ED; however, a pooled accuracy must be interpreted cautiously given substantial heterogeneity and that important patient and test characteristics affect its diagnostic performance.

Protocol Registration: PROSPERO (CRD42023392058).
Measuring the Effect of the Early assessment Team (MEET) for patients referred to outpatient mental health care: a study protocol for a randomised controlled trial
Authors: Kvestad Camilla Angelsen , Holte Ingvild Rønneberg , Reitan Solveig Klæbo , Chiappa Charlotte S. , Helle Gunn Karin , Skjervold Anne E. , Rosenlund Anne Marit A. , Watne Øyvind , Brattland Heidi , Helle Jon , Follestad Turid , Hara Karen Walseth , Holgersen Katrine Høyer
Published: March 2024

Background

Referrals to specialised mental health care (such as community mental health centres; CMHC) have increased over the last two decades. Patients often have multifaceted problems, which cannot only be solved by such care. Resources are limited, and triaging is challenging. A novel method which approaches patients early and individually upon referral to a CMHC—possibly with a brief intervention—is an Early assessment Team (EaT). In an EaT, two therapists meet the patient early in the process and seek to solve the present problem, often involving community services, primary health care, etc.; attention is paid to symptoms and functional strife, rather than diagnoses. This is in contrast to treatment as usual (TAU), where the patient (after being on a waiting list) meets one therapist, who focuses on history and situation to assign a diagnosis and eventually start a longitudinal treatment. The aim of this study is to describe and compare EaT and TAU regarding such outcomes as work and social adjustment, mental health, quality of life, use of health services, and patient satisfaction. The primary outcome is a change in perceived function from baseline to 12-month follow-up, measured by the Work and Social Adjustment Scale.

Method

Patients (18 years and above; n = 588) referred to outpatient health care at a CMHC are randomised to EaT or TAU. Measures (patient self-reports and clinician reports, patients’ records, and register data) are collected at baseline, after the first and last meeting, and at 2, 4, 8, 12, and 24 months after inclusion. Some participants will be invited to participate in qualitative interviews.

Trial design

The study is a single-centre, non-blinded, RCT with two conditions involving a longitudinal and mixed design (quantitative and qualitative data).

Discussion

This study will examine an intervention designed to determine early on which patients will benefit from parallel or other measures than assessment and treatment in CMHC and whether these will facilitate their recovery. Findings may potentially contribute to the development of the organisation of mental health services.

Trial registration

ClinicalTrials.gov NCT05087446. Registered on 21 October 2021.
A case–control study of the association between the gut microbiota and colorectal cancer: exploring the roles of diet, stress, and race
Authors: Carson Tiffany L. , Byrd Doratha A. , Smith Kristen S. , Carter Daniel , Gomez Maria , Abaskaron Michael , Little Rebecca B. , Holmes Sh’Nese Townsend , van Der Pol William J. , Lefkowitz Elliot J. , Morrow Casey D. , Fruge Andrew D.
Published: March 2024

Background

The gut microbiota is associated with risk for colorectal cancer (CRC), a chronic disease for which racial disparities persist with Black Americans having a higher risk of CRC incidence and mortality compared to other groups. Given documented racial differences, the gut microbiota may offer some insight into previously unexplained racial disparities in CRC incidence and mortality. A case–control analysis comparing 11 women newly diagnosed with CRC with 22 cancer-free women matched on age, BMI, and race in a 1:2 ratio was conducted. Information about participants’ diet and perceived stress levels were obtained via 24-h Dietary Recall and Perceived Stress Scale-10 survey, respectively. Participants provided stool samples from which microbial genomic DNA was extracted to reveal the abundance of 26 genera chosen a priori based on their previously observed relevance to CRC, anxiety symptoms, and diet.

Results

Significantly lower alpha diversity was observed among cancer-free Black women compared to all other race-cancer status combinations. No group differences were observed when comparing beta diversity. Non-Hispanic White CRC cases tended to have higher relative abundance of Fusobacteria, Gemellaceae, and Peptostreptococcus compared to all other race-cancer combination groups. Perceived stress was inversely associated with alpha diversity and was associated with additional genera.

Conclusions

Our findings suggest that microbiome-CRC associations may differ by racial group. Additional large, racially diverse population-based studies are needed to determine if previously identified associations between characteristics of the gut microbiome and CRC are generalizable to Black women and other racial, ethnic, and gender groups.
Greedy selection of sensors with measurements under correlated noise
Authors: Kim Yoon Hak
Published: March 2024

We address the sensor selection problem where linear measurements under correlated noise are gathered at the selected nodes to estimate the unknown parameter. Since finding the best subset of sensor nodes that minimizes the estimation error requires a prohibitive computational cost especially for a large number of nodes, we propose a greedy selection algorithm that uses the log-determinant of the inverse estimation error covariance matrix as the metric to be maximized. We further manipulate the metric by employing the QR and LU factorizations to derive a simple analytic rule which enables an efficient selection of one node at each iteration in a greedy manner. We also make a complexity analysis of the proposed algorithm and compare with different selection methods, leading to a competitive complexity of the proposed algorithm. For performance evaluation, we conduct numerical experiments using randomly generated measurements under correlated noise and demonstrate that the proposed algorithm achieves a good estimation accuracy with a reasonable selection complexity as compared with the previous novel selection methods.
High expression circRALGPS2 in atretic follicle induces chicken granulosa cell apoptosis and autophagy via encoding a new protein
Authors: He Haorong , Wei Yuanhang , Chen Yuqi , Zhao Xiyu , Shen Xiaoxu , Zhu Qing , Yin Huadong
Published: March 2024

Background

The reproductive performance of chickens mainly depends on the development of follicles. Abnormal follicle development can lead to decreased reproductive performance and even ovarian disease among chickens. Chicken is the only non-human animal with a high incidence of spontaneous ovarian cancer. In recent years, the involvement of circRNAs in follicle development and atresia regulation has been confirmed.

Results

In the present study, we used healthy and atretic chicken follicles for circRNA RNC-seq. The results showed differential expression of circRALGPS2. It was then confirmed that circRALGPS2 can translate into a protein, named circRALGPS2-212aa, which has IRES activity. Next, we found that circRALGPS2-212aa promotes apoptosis and autophagy in chicken granulosa cells by forming a complex with PARP1 and HMGB1.

Conclusions

Our results revealed that circRALGPS2 can regulate chicken granulosa cell apoptosis and autophagy through the circRALGPS2-212aa/PARP1/HMGB1 axis.
Trend mining with Orange – using topic modeling in futures research with the example of urban mobility
Authors: Sonk Matthias , Tunger Dirk
Published: March 2024

Today, assumptions about probable future developments (at least as far as they make use of quantifiable scientific methods and are not pure speculation) are generally based on data from the past. An interesting way to analyze the future through this type of data is text mining or individual methods out of the spectrum of text mining, such as topic modeling. Topic Modeling itself is a combination of quantitative and qualitative methodology and is based on the full spectrum of social science methodology. Therefore, the method is an interesting way for futures research to analyze futures. This publication addresses the question of how a combination of different methods can contribute to trend monitoring or trend mining. For this purpose, a set of scientific publications was first generated with the help of a search query in the Web of Science (WoS), which is the basis for all evaluations and statements and topics. In essence, the method considered here should be more fully integrated into the scientific practice of futures research because it can make a valuable contribution to estimating future development based on past development.
Dissociation in mothers with borderline personality disorder: a possible mechanism for transmission of intergenerational trauma? A scoping review
Authors: Rimmington David , Roberts Rachel , Sawyer Alyssa , Sved-Williams Anne
Published: March 2024

Background

Dissociation is a feature of Borderline Personality Disorder (BPD), but rarely a focus for research, particularly in the perinatal literature. BPD partly has its aetiology in childhood and is characterised by emotional changes and difficulty with self-coherence that impacts on the processes of caregiving.

Methods

A scoping review was conducted to synthesise current perspectives on the effect of dissociation in caregivers with BPD, particularly regarding the impact of caregiver dissociation on the interactional quality of relationship within parent–child dyads. Studies were included if they explicitly mentioned dissociation in the target population, or if dissociation was implied. A thematic analysis was conducted.

Results

20 studies were included; 10 experimental or quasi-experimental; 2 presenting case material; and 8 non-systematic review articles. 4 studies used the Dissociative Experiences Scale (DES) to measure dissociation, while 2 studies included a ‘dissociative behaviour’ subscale as part of an observational measure. The remaining studies did not measure dissociation but referenced directly or indirectly a concept of dissociation.

Conclusions

Findings suggested there was some evidence that dissociation plays a unique role in BPD caregivers’ interactions with their offspring, however any findings should be interpreted with caution as the concept has been poorly operationalised and defined.
Biomechanical analysis of total arch maxillary distalization using infrazygomatic crest miniscrews: a finite element analysis study
Authors: Schwertner Alessandro , de Almeida-Pedrin Renata Rodrigues , Poleti Thais Maria Freire Fernandes , Oltramari Paula , de Castro Conti Ana Cláudia Ferreira , Cotrim-Ferreira Flávio Augusto , de Almeida Guilherme , Flores-Mir Carlos , de Almeida Marcio Rodrigues
Published: March 2024

Aim

To evaluate the maxillary incisors and canine’s immediate movement tendency using three different power arms (PA) height levels during total arch maxillary distalization supported on infrazygomatic crest (IZC) miniscrews according to finite element analysis (FEA).

Methods

Three finite element models of the maxilla were developed based on CBCT imaging of a teenage male patient presenting a Class II Division 1 malocclusion in the early permanent dentition. Maxillary complex, periodontium, orthodontic accessories, IZC miniscrews and an orthodontic wire were digitally created. The PAs were placed between canines and lateral incisors and projected at 4, 7, and 10 mm height distances. After that, distalization forces were simulated between PA and IZC miniscrews.

Results

The anterior teeth deformation produced in the FEA models was assessed according to a Von Mises equivalent. The stress was measured, revealing tendencies of initial maxillary teeth movement. No differences were found between the right and left sides. However, there was a significant difference among models in the under-stress areas, especially the apical and cervical root areas of the maxillary anterior teeth. More significant extrusion and lingual tipping of incisors were observed with the 4 mm power arm compared to the 7 mm and 10 mm ones. The 10 mm power arm did not show any tendency for extrusion of maxillary central incisors but a tendency for buccal tipping and intrusion of lateral incisors.

Conclusion

The maxillary incisors and canines have different immediate movement tendencies according to the height of the anterior point of the en-masse distalization force application. Based on the PA height increase, a change from lingual to buccal tipping and less extrusion tendency was observed for the incisors, while the lingual tipping and extrusion trend for canines increased.
Breaking down barriers: comprehensive functional analysis of the Aspergillus niger chitin synthase repertoire
Authors: Barthel Lars , Cairns Timothy , Duda Sven , Müller Henri , Dobbert Birgit , Jung Sascha , Briesen Heiko , Meyer Vera
Published: March 2024

Background

Members of the fungal kingdom are heterotrophic eukaryotes encased in a chitin containing cell wall. This polymer is vital for cell wall stiffness and, ultimately, cell shape. Most fungal genomes contain numerous putative chitin synthase encoding genes. However, systematic functional analysis of the full chitin synthase catalogue in a given species is rare. This greatly limits fundamental understanding and potential applications of manipulating chitin synthesis across the fungal kingdom.

Results

In this study, we conducted in silico profiling and subsequently deleted all predicted chitin synthase encoding genes in the multipurpose cell factory Aspergillus niger. Phylogenetic analysis suggested nine chitin synthases evolved as three distinct groups. Transcript profiling and co-expression network construction revealed remarkably independent expression, strongly supporting specific role(s) for the respective chitin synthases. Deletion mutants confirmed all genes were dispensable for germination, yet impacted colony spore titres, chitin content at hyphal septa, and internal architecture of submerged fungal pellets. We were also able to assign specific roles to individual chitin synthases, including those impacting colony radial growth rates (ChsE, ChsF), lateral cell wall chitin content (CsmA), chemical genetic interactions with a secreted antifungal protein (CsmA, CsmB, ChsE, ChsF), resistance to therapeutics (ChsE), and those that modulated pellet diameter in liquid culture (ChsA, ChsB). From an applied perspective, we show chsF deletion increases total protein in culture supernatant over threefold compared to the control strain, indicating engineering filamentous fungal chitin content is a high priority yet underexplored strategy for strain optimization.

Conclusion

This study has conducted extensive analysis for the full chitin synthase encoding gene repertoire of A. niger. For the first time we reveal both redundant and non-redundant functional roles of chitin synthases in this fungus. Our data shed light on the complex, multifaceted, and dynamic role of chitin in fungal growth, morphology, survival, and secretion, thus improving fundamental understanding and opening new avenues for biotechnological applications in fungi.
Targeting vulnerable microcircuits in the ventral hippocampus of male transgenic mice to rescue Alzheimer-like social memory loss
Authors: Lei Hui-Yang , Pi Gui-Lin , He Ting , Xiong Rui , Lv Jing-Ru , Liu Jia-Le , Wu Dong-Qin , Li Meng-Zhu , Shi Kun , Li Shi-Hong , Yu Na-Na , Gao Yang , Yu Hui-Ling , Wei Lin-Yu , Wang Xin , Zhou Qiu-Zhi , Zou Pei-Lin , Zhou Jia-Yang , Liu Ying-Zhou , Shen Nai-Ting , Yang Jie , Ke Dan , Wang Qun , Liu Gong-Ping , Yang Xi-Fei , Wang Jian-Zhi , Yang Ying
Published: March 2024

Background

Episodic memory loss is a prominent clinical manifestation of Alzheimer’s disease (AD), which is closely related to tau pathology and hippocampal impairment. Due to the heterogeneity of brain neurons, the specific roles of different brain neurons in terms of their sensitivity to tau accumulation and their contribution to AD-like social memory loss remain unclear. Therefore, further investigation is necessary.

Methods

We investigated the effects of AD-like tau pathology by Tandem mass tag proteomic and phosphoproteomic analysis, social behavioural tests, hippocampal electrophysiology, immunofluorescence staining and in vivo optical fibre recording of GCaMP6f and iGABASnFR. Additionally, we utilized optogenetics and administered ursolic acid (UA) via oral gavage to examine the effects of these agents on social memory in mice.

Results

The results of proteomic and phosphoproteomic analyses revealed the characteristics of ventral hippocampal CA1 (vCA1) under both physiological conditions and AD-like tau pathology. As tau progressively accumulated, vCA1, especially its excitatory and parvalbumin (PV) neurons, were fully filled with mislocated and phosphorylated tau (p-Tau). This finding was not observed for dorsal hippocampal CA1 (dCA1). The overexpression of human tau (hTau) in excitatory and PV neurons mimicked AD-like tau accumulation, significantly inhibited neuronal excitability and suppressed distinct discrimination-associated firings of these neurons within vCA1. Photoactivating excitatory and PV neurons in vCA1 at specific rhythms and time windows efficiently ameliorated tau-impaired social memory. Notably, 1 month of UA administration efficiently decreased tau accumulation via autophagy in a transcription factor EB (TFEB)-dependent manner and restored the vCA1 microcircuit to ameliorate tau-impaired social memory.

Conclusion

This study elucidated distinct protein and phosphoprotein networks between dCA1 and vCA1 and highlighted the susceptibility of the vCA1 microcircuit to AD-like tau accumulation. Notably, our novel findings regarding the efficacy of UA in reducing tau load and targeting the vCA1 microcircuit may provide a promising strategy for treating AD in the future.
Development of a quality of work life scale for Japanese community pharmacists: a questionnaire survey mostly in large companies
Authors: Kato Yuta , Sekiya Takashi , Ishii Ryo , Hirako Yoji , Satoh Hiroki , Kimura Hiromichi
Published: March 2024

Background

Human resource management may become complex for community pharmacists owing to recent changes in work volume and content. Few studies have examined job satisfaction, well-being, and quality of work life (QWL) among community pharmacists in Japan. This study focused on QWL, a more comprehensive concept than job satisfaction, and aimed to develop the QWL questionnaire for Japanese community pharmacists (the QWLQ for JCP) and assess its reliability and validity.

Methods

A questionnaire survey was conducted among 2027 pharmacists who worked in pharmacies with the cooperation of 20 corporations running pharmacies. Collected data were subjected to principal component factor analysis with Promax rotation via SPSS Windows version 28.

Results

The factor analysis used data from 1966 pharmacists. In total, five significant components, which formed the basis of the QWLQ for JCP, were identified. These included “Influence of work on mind and body,” “Relationships with colleagues,” “Relationship with the boss,” “Meaning of existence in the workplace,” and “Pride in work.” Cronbach’s alpha, which expressed reliability, ranged from 0.585 to 0.854 for all the subscales.

Conclusion

The QWLQ for the JCP significantly explained the concept of QWL, which indicated that its validity was sufficient.
"An L2 Education without Love is not Education at All": a phenomenographic study of undergraduate EFL students’ perceptions of pedagogical love
Authors: Ghiasvand Farhad , Sharifpour Pardis
Published: March 2024

The role of pedagogical love in second language (L2) education has long remained under-explored due to dogmatic religious and cultural beliefs. There is insufficient scholarship on this construct at undergraduate levels. To bridge this gap, the present study employed a phenomenographic design to uncover Iranian undergraduate students’ perceptions of pedagogical love and its features, realizations, and determinant factors. It invited 22 undergraduate L2 learners to attend a semi-structured interview and complete a narrative frame. The results of content and thematic analysis attained through MAXQDA software (v. 20) revealed that the participants had different perceptions of pedagogical love. They considered it as a non-romantic intimacy and respect, deep care for students and their emotions, and pure love based on mutual trust. Furthermore, it was found that pedagogical love is essential for L2 education as characterized by a mutual trust and respect, kindness, care, bonding, intimacy, and forgiveness. Regarding its realizations, the results demonstrated that pedagogical love shows itself through intimacy, classroom engagement/participation, confidence, academic performance, and mutual care, respect, and responsibility. Moreover, it was identified that teachers’ emotional literacy, teachers’ pedagogical expertise, and positive classroom rapport facilitated the implementation of loving pedagogy at undergraduate level. Finally, the findings indicated that loving pedagogy practice was mostly precluded by strict religious beliefs, stigmatizing socio-cultural norms, emotion expression, fear, and traditional educational systems. Implications for L2 teachers and educators are discussed to augment their understanding of pedagogical love, as an opportunity to grasp the emotional side of language education.
Gene editing technology to improve antitumor T-cell functions in adoptive immunotherapy
Authors: Ito Yusuke , Inoue Satoshi , Kagoya Yuki
Published: March 2024

Adoptive immunotherapy, in which tumor-reactive T cells are prepared in vitro for adoptive transfer to the patient, can induce an objective clinical response in specific types of cancer. In particular, chimeric antigen receptor (CAR)-redirected T-cell therapy has shown robust responses in hematologic malignancies. However, its efficacy against most of the other tumors is still insufficient, which remains an unmet medical need. Accumulating evidence suggests that modifying specific genes can enhance antitumor T-cell properties. Epigenetic factors have been particularly implicated in the remodeling of T-cell functions, including changes to dysfunctional states such as terminal differentiation and exhaustion. Genetic ablation of key epigenetic molecules prevents the dysfunctional reprogramming of T cells and preserves their functional properties.

Clustered, regularly interspaced, short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas)-based gene editing is a valuable tool to enable efficient and specific gene editing in cultured T cells. A number of studies have already identified promising targets to improve the therapeutic efficacy of CAR-T cells using genome-wide or focused CRISPR screening. In this review, we will present recent representative findings on molecular insights into T-cell dysfunction and how genetic modification contributes to overcoming it. We will also discuss several technical advances to achieve efficient gene modification using the CRISPR and other novel platforms.
Neuroprotective effect of bromelain on BDNF-TRKB signalling pathway in chronic unpredictable stress-induced depression model
Authors: Parasuraman Rajeshwari , Jayamurali Dheepthi , Manoharan Nivedita , Govindarajalu Sathya Narayanan
Published: March 2024

Background

Bromelain is a mixture of protease enzyme extract from the fruit or stem of the pineapple plant. It has a wide range of biological actions, and it is most commonly used as an anti-inflammatory agent. This study was designed to investigate the antidepressant effect of bromelain on chronic unpredictable stress (CUS)-induced depression in rat models by targeting various molecular mechanisms.

Result

We studied the in silico analysis of the antidepressant potential of bromelain by docking with various proteins involved in the pathophysiology of depression. As a result of in silico studies, bromelain showed good binding energy with IL1β, 5-HT, BDNF, CREB, and TrkB. The mRNA expression of BDNF, TrkB, AKT, ERK, and IL-1β was studied by qRT-PCR. Gene expression studies showed a significant decrease in BDNF, TrkB, AKT, and ERK in chronic unpredictable stress, whereas there was a significant increase in the case of the bromelain- and fluoxetine-treated group. Since neuroinflammation is also one of the major concerns in the pathophysiology of depression, pro-inflammatory cytokines were also studied along with apoptotic markers using ELISA. ELISA results showed a significant increase in inflammatory cytokines in CUS, and it was significantly decreased in the case of the bromelain- and fluoxetine-treated group. Similarly, there was an increased concentration of pro-apoptotic protein in the CUS group, whereas it was decreased in the bromelain and fluoxetine groups.

Conclusions

From the results, it is clear that bromelain exerts an antidepressive effect by preventing neuroinflammation and neurodegeneration and by enhancing neurogenesis and neuroplasticity.

Graphical abstract
Loneliness in adolescence and prescription of psychotropic drugs in adulthood: 23-year longitudinal population-based and registry study
Authors: Rodríguez-Cano Rubén , Lotre Karianne , von Soest Tilmann , Rognli Eline Borger , Bramness Jørgen Gustav
Published: March 2024

Background

The role of adolescent loneliness in adult mental health and prescriptions of psychotropic drugs remains underexplored.

Aims

We aim to determine whether (a) experiencing loneliness in adolescence and (b) changes in loneliness from adolescence to adulthood are prospectively associated with prescriptions for a variety of psychotropic drugs in adulthood.

Method

We used data from a Norwegian population-based sample with 2602 participants, collected across four waves between 1992 and 2006. Loneliness was assessed at each wave, with survey data linked to medicinal drug prescription records from the Norwegian Prescription Database. We identified prescription histories of antipsychotics, mood stabilisers, antidepressants and benzodiazepines from 2007 to 2015, for each participant. We use latent growth curve analyses to model the relationship of adolescent loneliness and loneliness change from adolescence to adulthood, with subsequent psychotropic drugs prescription.

Results

Adolescents with heightened loneliness, and adolescents whose loneliness increased into young adulthood, had a greater likelihood of being prescribed antipsychotics, mood stabilisers and antidepressants in adulthood. These associations remained significant after adjustment for confounders such as sociodemographic characteristics, conduct problems, substance use and mental health problems.

Conclusions

Loneliness in adolescence and its adverse development over a span of 15 years was linked to higher risk of receiving prescriptions for antipsychotics, mood stabilisers and antidepressants later in life. The findings may indicate that loneliness increases the risk for developing psychotic disorders, bipolar disorders and major depression.
The Effects of Peri-Operative Adverse Events on Clinical and Patient-Reported Outcomes After Surgery for Degenerative Cervical Myelopathy: An Observational Cohort Study from the Canadian Spine Outcomes and Research Network
Authors: Malhotra Armaan K. , Evaniew Nathan , Dea Nicolas , Fisher Charles G. , Street John T. , Cadotte David W. , Jacobs W. Bradley , Thomas Kenneth C. , Attabib Najmedden , Manson Neil , Hall Hamilton , Bailey Christopher S. , Nataraj Andrew , Phan Philippe , Rampersaud Y Raja , Paquet Jerome , Weber Michael H. , Christie Sean D. , McIntosh Greg , Wilson Jefferson R.
Published: March 2024

BACKGROUND AND OBJECTIVES:

There is a lack of data examining the effects of perioperative adverse events (AEs) on long-term outcomes for patients undergoing surgery for degenerative cervical myelopathy. We aimed to investigate associations between the occurrence of perioperative AEs and coprimary outcomes: (1) modified Japanese Orthopaedic Association (mJOA) score and (2) Neck Disability Index (NDI) score.

METHODS:

We analyzed data from 800 patients prospectively enrolled in the Canadian Spine Outcomes and Research Network multicenter observational study. The Spine AEs Severity system was used to collect intraoperative and postoperative AEs. Patients were assessed at up to 2 years after surgery using the NDI and the mJOA scale. We used a linear mixed-effect regression to assess the influence of AEs on longitudinal outcome measures as well as multivariable logistic regression to assess factors associated with meeting minimal clinically important difference (MCID) thresholds at 1 year.

RESULTS:

There were 167 (20.9%) patients with minor AEs and 36 (4.5%) patients with major AEs. The occurrence of major AEs was associated with an average increase in NDI of 6.8 points (95% CI: 1.1-12.4, P = .019) and reduction of 1.5 points for mJOA scores (95% CI: −2.3 to −0.8, P < .001) up to 2 years after surgery. Occurrence of major AEs reduced the odds of patients achieving MCID targets at 1 year after surgery for mJOA (odds ratio 0.23, 95% CI: 0.086-0.53, P = .001) and for NDI (odds ratio 0.34, 95% CI: 0.11-0.84, P = .032).

CONCLUSION:

Major AEs were associated with reduced functional gains and worse recovery trajectories for patients undergoing surgery for degenerative cervical myelopathy. Occurrence of major AEs reduced the probability of achieving mJOA and NDI MCID thresholds at 1 year. Both minor and major AEs significantly increased health resource utilization by reducing the proportion of discharges home and increasing length of stay.
Manipulation of the nuclear envelope-associated protein SLAP during mammalian brain development affects cortical lamination and exploratory behavior
Authors: Mestres Ivan , Atabay Azra , Escolano Joan-Carles , Arndt Solveig , Schmidtke Klara , Einsiedel Maximilian , Patsonis Melina , Bolaños-Castro Lizbeth Airais , Yun Maximina , Bernhardt Nadine , Taubenberger Anna , Calegari Federico
Published: March 2024

Here, we report the first characterization of the effects resulting from the manipulation of Soluble-Lamin Associated Protein (SLAP) expression during mammalian brain development. We found that SLAP localizes to the nuclear envelope and when overexpressed causes changes in nuclear morphology and lengthening of mitosis. SLAP overexpression in apical progenitors of the developing mouse brain altered asymmetric cell division, neurogenic commitment and neuronal migration ultimately resulting in unbalance in the proportion of upper, relative to deeper, neuronal layers. Several of these effects were also recapitulated upon Cas9-mediated knockdown. Ultimately, SLAP overexpression during development resulted in a reduction in subcortical projections of young mice and, notably, reduced their exploratory behavior. Our study shows the potential relevance of the previously uncharacterized nuclear envelope protein SLAP in neurodevelopmental disorders.
Epidemiological behavior of childhood obesity: A continental point of view
Authors: Chacin Maricarmen , Carrillo-Sierra Sandra , Duran Pablo , Garrido Bermany , Carrasquero Ruben , Nava Manuel , Salazar Juan , Angarita Lisse , Anderson Hazel , Garcia-Pacheco Henry , Checa-Ros Ana , D’Marco Luis , Rivera-Porras Diego , Bermúdez Valmore
Published: March 2024

Weight excess during the childhood has been one of the most critical public health problems worldwide in the past few decades. It is considered a significant predictor of adulthood obesity, increased cardiometabolic diseases, and premature mortality. Since the Industrial Revolution, childhood obesity has risen due to sedentary lifestyles and poor eating habits, contributing to the development of obesogenic environments around children in different parts of the world. In this regard, Oceania is positioned as the continent with the highest prevalence globally; however, these results did not consider Australia and New Zealand’s data, probably due to the significant differences in population sizes. America has the second highest percentage of children under five who are overweight. Curiously, Asia’s obesity rates are more significant in higher socioeconomic statuses and urban areas than in children aged 2-4 years. Likewise, Africa displays similar epidemiologic behaviour. Qatar and Kuwait are the countries with the highest obesity prevalence on the continent. Moreover, Europe exhibits a notable South-North gradient, which establishes a higher prevalence of obesity in Mediterranean countries than the Nordic ones. In this regard, various prevention and interventional programs have been developed to combat this silent epidemic, focusing their efforts on nutritional education, improving children’s and parents’ lifestyles, and fighting the influence of the media on their behaviour, and decisions. Therefore, the objective of this review was to describe the epidemiological behaviour of childhood obesity from a continental perspective.
Poor quality of sleep and it's associated factors among urban slum-dwellers of Bengaluru- a cross-sectional study
Authors: Rao Mithun , Bhushan Shobha , TS Ranganath
Published: March 2024

Background Sleep can be defined as a state of reduced attention from where the person can be woken up by any kind of stimuli. Sleep difficulties are a major group of disorders affecting one third of the adult population. The present study was taken up to assess the sleep quality and prevalence of sleep disorders among the adult population in the urban slum area of H Siddaiah Road Urban Primary Health Center (UPHC), which is in the Urban Field Practice Area, BMCRI. Methods Stratified random sampling was used to select 821 adults in the population of 18-60 years of age. Ethical clearance was obtained from the Institutional Ethical Committee. A pretested semi-structured questionnaire was used to interview the adults after obtaining their consent. The data was entered in Microsoft Office Excel and analysed using SPSS ver20.0. Results The study population was 52.81% females and 77.5% in the age group of 18-30 years. Most of the study population were Hindus (78.90%), and only 3.8% of the study population were illiterate. Most of them were employed (86.12%). Substance use was present in 82.9% of the study participants and overcrowding was present in 51.3% of the subjects. Female gender, being unemployed, living with relatives, overcrowding, and substance use such as alcohol and smokeless tobacco were the factors associated with poor sleep quality as measured using the Pittsburgh Sleep Quality Index. Among the study participants having poor sleep quality, most of participants needed further clinical assessment for insomnia (86%) followed by assessment for sleep apnoea (50.5%). Conclusions 200 (24.36%) study participants were determined to have poor sleep quality. Gender, marital status and overcrowding were the factors associated with poor sleep quality. A significant number of study participants need further assessment on insomnia, sleep apnoea and psychiatric disorders.
Prospective effect of linkers type on the anticancer activity of pemetrexed-monoclonal antibody (atezolizumab) conjugates
Authors: Ibraheem Faten Q. , Maraie Nidhal K. , Al-Sudani Basma Talib , Raauf Ayad M.R.
Published: March 2024

Background Conventional chemotherapy results in severe toxic side effects due to affecting normal and cancer cells. The conjugation of chemotherapy with mAb will improve the chemotherapy selectivity towards cancer cells and at the same time will potentiate immune system to detect and kill cancer cells. The aim of the study was to prepare atezolizumab-pemetrexed conjugate using two types of linkers (linker conjugated with -NH2 of lysine amino acid in the mAb). Methods This study utilizes (for the first time) the mAb atezolizumab (AtZ) to prepare a new, selective conjugate carrier for pemetrexed (PMX) by using gamma amino butyric acid (GABA) as linker for the first time in comparison to the commonly used linker polyethylene glycol (PEG) using carbodiimide (EDC) / N-hydroxysulfosuccinimide (Sulfo-NHS) zero length cross linker. Stepwise evaluation for PMX-linkers linkage as well as mAb conjugates was evaluated by FTIR, 1HNMR, DSC, LC-MS, gel-electrophoresis as well as the anticancer activity against lung cells A549. Results The work revealed that two molecules of GABA combined with PMX, which in turn conjugated with an average ratio of 4:1 with mAb, while one molecule of PEG combined with PMX, which in turn conjugated with mAb in the same average ratio. The IC50 for the prepared PMX-GABA-AtZ conjugate was 0.048 µM, which was much lower than PMX alone, antibody AtZ alone as well as PMX-PEG-AtZ conjugate in a dose and time dependent manner. Conclusions The potential use of such conjugate that selectively directed to the overexpressed lung cells antigen in a low dose leading to reduction of serious side effects of PMX and the cost of therapeutically AtZ mAb used.