bluuebunny/crossref_metadata_2025 huggingface dataset:
A Case Study of a Post-Acquisition Organizational Healing Intervention: Enablers and Outcomes
Authors: Agrawal Aditya , Pandey Ashish , Kumar Payal
Published: March 2024

This qualitative study examines the effectiveness of an organization-wide healing intervention that aimed to fortify an uncertain relationship that existed between the new management and existing employees in a post-acquisition scenario. There was an inherent tension in the relationship, because the sociocultural sensibilities were at variance, with the acquiring management team being from the developed western part of India while the employees were from an emerging economy state from eastern India. From the content analysis of interviews of respondents at various organizational levels, this study identified enablers facilitating the healing process at the individual and collective levels. In fact, three types of enablers of organizational healing were identified: Leadership-linked, social and cultural. This study’s key finding is that these enablers elicit mid-level healing outcomes, which in the long run are likely to result in improved organizational outcomes.
Navigating Pakistan’s Religious, Social and Political Fault Lines in the 1980s: Contemporary Trends and Relevance
Authors: Siddiqi Farhan Hanif
Published: March 2024

How do sociopolitical developments in the 1980s endure in contemporary Pakistan? The article answers this question across three dimensions: first, the religious, as witnessed in General Zia-ul-Haq’s weaponization of blasphemy laws that shaped the rise of a majoritarian political actor in the shape of the Tehreek-e-Labbaik Pakistan (TLP) in 2017. Second, the social, with Zia-ul-Haq’s Islamization laws denigrating the agency of women leading to their resolute mobilization in the 1980s and again in 2018 in the shape of the Aurat March and Aurat Azadi March movements. Finally, the political, where the military takeover in 1977 invited a counter-movement in the form of the Movement for the Restoration of Democracy (MRD) in 1981. In 2020, opposition parties formed the Pakistan Democratic Movement (PDM) as a counterweight to the incumbent civil-military hybrid regime. The article concludes that Pakistan’s failure to improve on the religious, societal and political indicators lies at the core of its dishevelled polity.
Loss of Dnmt3a increases self-renewal and resistance to pegIFN-α in JAK2-V617F–positive myeloproliferative neoplasms
Authors: Usart Marc , Stetka Jan , Luque Paz Damien , Hansen Nils , Kimmerlin Quentin , Almeida Fonseca Tiago , Lock Melissa , Kubovcakova Lucia , Karjalainen Riikka , Hao-Shen Hui , Börsch Anastasiya , El Taher Athimed , Schulz Jessica , Leroux Jean-Christophe , Dirnhofer Stefan , Skoda Radek C.
Published: March 2024

Pegylated interferon alfa (pegIFN-α) can induce molecular remissions in patients with JAK2-V617F–positive myeloproliferative neoplasms (MPNs) by targeting long-term hematopoietic stem cells (LT-HSCs). Additional somatic mutations in genes regulating LT-HSC self-renewal, such as DNMT3A, have been reported to have poorer responses to pegIFN-α. We investigated whether DNMT3A loss leads to alterations in JAK2-V617F LT-HSC functions conferring resistance to pegIFN-α treatment in a mouse model of MPN and in hematopoietic progenitors from patients with MPN. Long-term treatment with pegIFN-α normalized blood parameters and reduced splenomegaly and JAK2-V617F chimerism in single-mutant JAK2-V617F (VF) mice. However, pegIFN-α in VF;Dnmt3aΔ/Δ (VF;DmΔ/Δ) mice worsened splenomegaly and failed to reduce JAK2-V617F chimerism. Furthermore, LT-HSCs from VF;DmΔ/Δ mice compared with VF were less prone to accumulate DNA damage and exit dormancy upon pegIFN-α treatment. RNA sequencing showed that IFN-α induced stronger upregulation of inflammatory pathways in LT-HSCs from VF;DmΔ/Δ than from VF mice, indicating that the resistance of VF;DmΔ/Δ LT-HSC was not due to failure in IFN-α signaling. Transplantations of bone marrow from pegIFN-α–treated VF;DmΔ/Δ mice gave rise to more aggressive disease in secondary and tertiary recipients. Liquid cultures of hematopoietic progenitors from patients with MPN with JAK2-V617F and DNMT3A mutation showed increased percentages of JAK2-V617F–positive colonies upon IFN-α exposure, whereas in patients with JAK2-V617F alone, the percentages of JAK2-V617F–positive colonies decreased or remained unchanged. PegIFN-α combined with 5-azacytidine only partially overcame resistance in VF;DmΔ/Δ mice. However, this combination strongly decreased the JAK2-mutant allele burden in mice carrying VF mutation only, showing potential to inflict substantial damage preferentially to the JAK2-mutant clone.
Integration of ζ-deficient CARs into the CD3
ζ gene conveys potent cytotoxicity in T and NK cells
Authors: Kath Jonas , Franke Clemens , Drosdek Vanessa , Du Weijie , Glaser Viktor , Fuster-Garcia Carla , Stein Maik , Zittel Tatiana , Schulenberg Sarah , Porter Caroline E. , Andersch Lena , Künkele Annette , Alcaniz Joshua , Hoffmann Jens , Abken Hinrich , Abou-el-Enein Mohamed , Pruß Axel , Suzuki Masataka , Cathomen Toni , Stripecke Renata , Volk Hans-Dieter , Reinke Petra , Schmueck-Henneresse Michael , Wagner Dimitrios L.
Published: March 2024

Chimeric antigen receptor (CAR)-redirected immune cells hold significant therapeutic potential for oncology, autoimmune diseases, transplant medicine, and infections. All approved CAR-T therapies rely on personalized manufacturing using undirected viral gene transfer, which results in nonphysiological regulation of CAR-signaling and limits their accessibility due to logistical challenges, high costs and biosafety requirements. Random gene transfer modalities pose a risk of malignant transformation by insertional mutagenesis. Here, we propose a novel approach utilizing CRISPR-Cas gene editing to redirect T cells and natural killer (NK) cells with CARs. By transferring shorter, truncated CAR-transgenes lacking a main activation domain into the human CD3ζ (CD247) gene, functional CAR fusion-genes are generated that exploit the endogenous CD3ζ gene as the CAR’s activation domain. Repurposing this T/NK-cell lineage gene facilitated physiological regulation of CAR expression and redirection of various immune cell types, including conventional T cells, TCRγ/δ T cells, regulatory T cells, and NK cells. In T cells, CD3ζ in-frame fusion eliminated TCR surface expression, reducing the risk of graft-versus-host disease in allogeneic off-the-shelf settings. CD3ζ-CD19-CAR-T cells exhibited comparable leukemia control to TCRα chain constant (TRAC)-replaced and lentivirus-transduced CAR-T cells in vivo. Tuning of CD3ζ-CAR-expression levels significantly improved the in vivo efficacy. Notably, CD3ζ gene editing enabled redirection of NK cells without impairing their canonical functions. Thus, CD3ζ gene editing is a promising platform for the development of allogeneic off-the-shelf cell therapies using redirected killer lymphocytes.
An international learning collaborative phase 2 trial for haploidentical bone marrow transplant in sickle cell disease
Authors: Kassim Adetola A. , de la Fuente Josu , Nur Erfan , Wilkerson Karina L. , Alahmari Ali D. , Seber Adriana , Bonfim Carmem , Simões Belinda Pinto , Alzahrani Mohsen , Eckrich Michael J. , Horn Biljana , Hanna Rabi , Dhedin Nathalie , Rangarajan Hemalatha G. , Gouveia Roseane Vasconcelos , Almohareb Fahad , Aljurf Mahmoud , Essa Mohammed , Alahmari Bader , Gatwood Katie , Connelly James A. , Dovern Elisabeth , Rodeghier Mark , DeBaun Michael R.
Published: March 2024

In the setting of a learning collaborative, we conducted an international multicenter phase 2 clinical trial testing the hypothesis that nonmyeloablative–related haploidentical bone marrow transplant (BMT) with thiotepa and posttransplant cyclophosphamide (PTCy) will result in 2-year event-free survival (no graft failure or death) of at least 80%. A total of 70 participants were evaluable based on the conditioning protocol. Graft failure occurred in 8 of 70 (11.4%) and only in participants aged <18 years; all had autologous reconstitution. After a median follow-up of 2.4 years, the 2-year Kaplan-Meier–based probability of event-free survival was 82.6%. The 2-year overall survival was 94.1%, with no difference between children and adult participants. After excluding participants with graft failure (n = 8), participants with engraftment had median whole blood donor chimerism values at days +180 and +365 after transplant of 100% (n = 58), respectively, and 96.6% (57/59) were off immunosuppression 1 year after transplant. The 1-year grade 3 to 4 acute graft-versus-host disease (GVHD) rate was 10%, and the 2-year moderate–severe chronic GVHD rate was 10%. Five participants (7.1%) died from infectious complications. We demonstrate that nonmyeloablative haploidentical BMT with thiotepa and PTCy is a readily available curative therapy for most adults, even those with organ damage, compared to the more expensive myeloablative gene therapy and gene editing. Additional strategies are required for children to decrease graft failure rates. The trial was registered at www.clinicaltrials.gov as #NCT01850108.
Management of adult patients with CMML undergoing allo-HCT: recommendations from the EBMT PH&G Committee
Authors: Onida Francesco , Gagelmann Nico , Chalandon Yves , Kobbe Guido , Robin Marie , Symeonidis Argiris , de Witte Theo , Itzykson Raphael , Jentzsch Madlen , Platzbecker Uwe , Santini Valeria , Sanz Guillermo , Scheid Christof , Solary Eric , Valent Peter , Greco Raffaela , Sanchez-Ortega Isabel , Yakoub-Agha Ibrahim , Pleyer Lisa
Published: March 2024

Chronic myelomonocytic leukemia (CMML) is a heterogeneous disease presenting with either myeloproliferative or myelodysplastic features. Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only potentially curative option, but the inherent toxicity of this procedure makes the decision to proceed to allo-HCT challenging, particularly because patients with CMML are mostly older and comorbid. Therefore, the decision between a nonintensive treatment approach and allo-HCT represents a delicate balance, especially because prospective randomized studies are lacking and retrospective data in the literature are conflicting. International consensus on the selection of patients and the ideal timing of allo-HCT, specifically in CMML, could not be reached in international recommendations published 6 years ago. Since then, new, CMML-specific data have been published. The European Society for Blood and Marrow Transplantation (EBMT) Practice Harmonization and Guidelines (PH&G) Committee assembled a panel of experts in the field to provide the first best practice recommendations on the role of allo-HCT specifically in CMML. Recommendations were based on the results of an international survey, a comprehensive review of the literature, and expert opinions on the subject, after structured discussion and circulation of recommendations. Algorithms for patient selection, timing of allo-HCT during the course of the disease, pretransplant strategies, allo-HCT modality, as well as posttransplant management for patients with CMML were outlined. The keynote message is, that once a patient has been identified as a transplant candidate, upfront transplantation without prior disease-modifying treatment is preferred to maximize chances of reaching allo-HCT whenever possible, irrespective of bone marrow blast counts.
Glyphosate lessons: is biodegradation of pesticides a harmless process for biodiversity?
Authors: Lozano Verónica Laura , Pizarro Haydée Norma
Published: March 2024

The historical perspective on the rapid biodegradation of pesticides as a mitigating factor in environmental risk assessment is reexamined through the example of glyphosate and its implications for freshwater biodiversity. Commonly employed standardized methods by national agencies for assessing the environmental risk of pesticides predominantly rely on single-species tests, overlooking the intricate nature of ecosystems. Glyphosate, one of the most widely used pesticides marketed for its purported rapid biodegradability, is often perceived as relatively innocuous. However, its degradation releases phosphorus into the environment, inducing a trophic state shift in water systems towards more eutrophic conditions, consequently affecting water quality. These findings highlight the cascading ecological repercussions of glyphosate biodegradation, driving the proliferation of specific aquatic organisms, such as picocyanobacteria and metaphyton, resulting in the alteration of ecosystem structure and dynamics. The study explores challenges posed by commercial pesticide formulations and investigates the consequences of pesticide interactions with specific anthropogenic factors. A case in point is the interaction of glyphosate with the invasive mussel Limnoperna fortunei, exacerbating the overall scenario. The ecological framework analyzed challenges the conventional notion that pesticide biodegradation is inherently a neutral or positive event. The results underscore the necessity of reassessing the role of biodegradation itself in environmental impact assessments for pesticides.
An analysis of published study designs in PubMed prisoner health abstracts from 1963 to 2023: a text mining study
Authors: Karystianis George , Lukmanjaya Wilson , Buchan Iain , Simpson Paul , Ginnivan Natasha , Nenadic Goran , Butler Tony
Published: March 2024

Background

The challenging nature of studies with incarcerated populations and other offender groups can impede the conduct of research, particularly that involving complex study designs such as randomised control trials and clinical interventions. Providing an overview of study designs employed in this area can offer insights into this issue and how research quality may impact on health and justice outcomes.

Methods

We used a rule-based approach to extract study designs from a sample of 34,481 PubMed abstracts related to epidemiological criminology published between 1963 and 2023. The results were compared against an accepted hierarchy of scientific evidence.

Results

We evaluated our method in a random sample of 100 PubMed abstracts. An F1-Score of 92.2% was returned. Of 34,481 study abstracts, almost 40.0% (13,671) had an extracted study design. The most common study design was observational (37.3%; 5101) while experimental research in the form of trials (randomised, non-randomised) was present in 16.9% (2319). Mapped against the current hierarchy of scientific evidence, 13.7% (1874) of extracted study designs could not be categorised. Among the remaining studies, most were observational (17.2%; 2343) followed by systematic reviews (10.5%; 1432) with randomised controlled trials accounting for 8.7% (1196) of studies and meta-analysis for 1.4% (190) of studies.

Conclusions

It is possible to extract epidemiological study designs from a large-scale PubMed sample computationally. However, the number of trials, systematic reviews, and meta-analysis is relatively small – just 1 in 5 articles. Despite an increase over time in the total number of articles, study design details in the abstracts were missing. Epidemiological criminology still lacks the experimental evidence needed to address the health needs of the marginalized and isolated population that is prisoners and offenders.
Predicting health outcomes with intensive longitudinal data collected by mobile health devices: a functional principal component regression approach
Authors: Yang Qing , Jiang Meilin , Li Cai , Luo Sheng , Crowley Matthew J. , Shaw Ryan J.
Published: March 2024

Background

Intensive longitudinal data (ILD) collected in near real time by mobile health devices provide a new opportunity for monitoring chronic diseases, early disease risk prediction, and disease prevention in health research. Functional data analysis, specifically functional principal component analysis, has great potential to abstract trends in ILD but has not been used extensively in mobile health research.

Objective

To introduce functional principal component analysis (fPCA) and demonstrate its potential applicability in estimating trends in ILD collected by mobile heath devices, assessing longitudinal association between ILD and health outcomes, and predicting health outcomes.

Methods

fPCA and scalar-to-function regression models were reviewed. A case study was used to illustrate the process of abstracting trends in intensively self-measured blood glucose using functional principal component analysis and then predicting future HbA1c values in patients with type 2 diabetes using a scalar-to-function regression model.

Results

Based on the scalar-to-function regression model results, there was a slightly increasing trend between daily blood glucose measures and HbA1c. 61% of variation in HbA1c could be predicted by the three preceding months’ blood glucose values measured before breakfast (P < 0.0001,$${R}_{adjusted}^{2}=0.61$$).

Conclusions

Functional data analysis, specifically fPCA, offers a unique tool to capture patterns in ILD collected by mobile health devices. It is particularly useful in assessing longitudinal dynamic association between repeated measures and outcomes, and can be easily integrated in prediction models to improve prediction precision.
Nonalcoholic fatty liver disease is an independent risk factor for ischemic stroke after revascularization in patients with Moyamoya disease: a prospective cohort study
Authors: Zhang Bojian , Li Junsheng , Zeng Chaofan , Tao Chuming , He Qiheng , Liu Chenglong , Zheng Zhiyao , Zhao Zhikang , Mou Siqi , Sun Wei , Wang Jia , Zhang Qian , Wang Rong , Zhang Yan , Ge Peicong , Zhang Dong
Published: March 2024

Background

The study aimed to investigate the association between nonalcoholic fatty liver disease (NAFLD) and ischemic stroke events after revascularization in patients with Moyamoya disease (MMD).

Methods

This study prospectively enrolled 275 MMD patients from September 2020 to December 2021. Patients with alcoholism and other liver diseases were excluded. NAFLD was confirmed by CT imaging or abdominal ultrasonography. Stroke events and modified Rankin Scale (mRS) scores at the latest follow-up were compared between the two groups.

Results

A total of 275 patients were enrolled in the study, among which 65 were diagnosed with NAFLD. Univariate logistic regression analysis showed that NAFLD (P = 0.029) was related to stroke events. Multivariate logistic regression analysis showed that NAFLD is a predictor of postoperative stroke in MMD patients (OR = 27.145, 95% CI = 2.031–362.81, P = 0.013). Kaplan-Meier analysis showed that compared with MMD patients with NAFLD, patients in the control group had a longer stroke-free time (P = 0.004). Univariate Cox analysis showed that NAFLD (P = 0.016) was associated with ischemic stroke during follow-up in patients with MMD. Multivariate Cox analysis showed that NAFLD was an independent risk factor for stroke in patients with MMD (HR = 10.815, 95% CI = 1.259–92.881, P = 0.030). Furthermore, fewer patients in the NAFLD group had good neurologic status (mRS score ≤ 2) than the control group (P = 0.005).

Conclusion

NAFLD was an independent risk factor for stroke in patients with MMD after revascularization and worse neurological function outcomes.
scRNA-seq analysis discovered suppression of immunomodulatory dependent inflammatory response in PMBCs exposed to silver nanoparticles
Authors: Perumalsamy Haribalan , Xiao Xiao , Kim Hyun-Yi , Yoon Tae-Hyun
Published: March 2024

The assessment of AgNPs toxicity in vitro and in vivo models are frequently conflicting and inaccurate. Nevertheless, single cell immunological responses in a heterogenous environment have received little attention. Therefore, in this study, we have performed in-depth analysis which clearly revealed cellular-metal ion association as well as specific immunological response. Our study didn’t show significant population differences in PMBC between control and AgNPs group implying no toxicological response. To confirm it further, deep profiling identified differences in subsets and differentially expressed genes (DEGs) of monocytes, B cells and T cells. Notably, monocyte subsets showed significant upregulation of metallothionein (MT) gene expression such as MT1G, MT1X, MT1E, MT1A, and MT1F. On the other hand, downregulation of pro-inflammatory genes such as IL1β and CCL3 in both CD16 + and CD16- monocyte subsets were observed. This result indicated that AgNPs association with monocyte subsets de-promoted inflammatory responsive genes suggesting no significant toxicity observed in AgNPs treated group. Other cell types such as B cells and T cells also showed negligible differences in their subsets suggesting no toxicity response. Further, AgNPs treated group showed upregulation of cell proliferation, ribosomal synthesis, downregulation of cytokine release, and T cell differentiation inhibition. Overall, our results conclude that treatment of AgNPs to PMBC cells didn’t display immunological related cytotoxicity response and thus motivate researchers to use them actively for biomedical applications.
Factors influencing rapid antiretroviral therapy initiation in Jiulongpo, Chongqing, China: a retrospective cohort from 2018 to 2022
Authors: Chen Cheng , Chen Hao , Wu Lingli , Gong Qin , He Jingchun
Published: March 2024

Background

Antiretroviral Therapy (ART) is pivotal in extending the lives of people living with HIV (PLWH) and minimizing transmission. Rapid ART initiation, defined as commencing ART within seven days of HIV diagnosis, is recommended for all PLWH.

Method

A retrospective cohort study was conducted using data from the China Information System for Disease Control and Prevention. This study included PLWH diagnosed between January 2018 and December 2021 and treated by December 2022. Factors influencing rapid ART initiation were examined using univariate and multivariate Cox regression analyses.

Results

The study analyzed 1310 cases. The majority were male (77.4%), over 50 years old (46.7%), and contracted HIV through heterosexual transmission (70.0%). Rapid ART initiation was observed in 36.6% (n = 479) of cases, with a cumulative treatment rate of 72.9% within 30 days post-diagnosis. Heterosexual contact was associated with longer intervals from diagnosis to treatment initiation compared to homosexual contact (Adjusted Hazard Ratio (HR) = 0.813, 95% Confidence Interval (CI): 0.668–0.988). Individuals older than 50 years (Adjusted HR = 1.852, 95%CI: 1.149–2.985) were more likely to initiate ART rapidly. Conversely, treatment at the Second Public Hospital (Adjusted HR = 0.483, 95% CI: 0.330–0.708) and a CD4 cell counts above 500 (Adjusted HR = 0.553, 95% CI: 0.332–0.921) were associated with a lower likelihood of initiating treatment within seven days.

Conclusions

A higher CD4 cell counts and receiving care in local public hospitals may deter rapid ART initiation. Providing CD4 counts results at diagnosis and offering testing and treatment in the same facility could enhance the rate of rapid ART initiation.
Giant stone adhered in the vaginal cavity in a female patient with type 2 diabetes mellitus: a case report
Authors: Alas-Pineda César , Gaitán-Zambrano Kristhel , Paredes Génesis Sarahí Chávez , Cárcamo-Portillo Gloria , Argeñal-Guifarro Hilda A. , Zúñiga-Girón Luis
Published: March 2024

Background

Bladder lithiasis comprises 5% of urological lithiasis. Large bladder stones associated with vesicovaginal fistulas are rare, and the risk factors are not an isolated process. There are metabolic comorbidities associated with this pathology, including diabetes mellitus.

Case presentation

A 70-year-old Mestizo patient is presented, reporting dysuria, pollakiuria, and abdominal pain of 4 months of evolution, located in the hypogastric region, also with a sensation of a foreign body in the vaginal introitus. In her pathological history, she presented type 2 diabetes mellitus. A computed tomography scan of the abdomen and pelvis was performed, reporting a tumor lesion in the abdominal wall. Therefore, surgical intervention was performed by cystolithotomy, obtaining a giant stone adhered to the vaginal wall with a size of 10 cm × 12 cm.

Conclusion

Early detection of this pathology should be exhaustive in patients with characteristics and comorbidities associated with stone development to avoid possible complications, such as vesicovaginal fistulas.
Indoxacarb poisoning causing methemoglobinemia treated with parenteral vitamin C: a case report
Authors: Sivanandam Lokesh Koumar , Arunkumar H. , Marlecha Pranay , Madamanchi Varsha , Maheshwari Chanchal , Naseer Mohammed Quader , Sanker Vivek , Dave Tirth
Published: March 2024

Introduction

This case study reports on a suicide attempt involving indoxacarb and vitamin C. Indoxacarb is a neurotoxic insecticide used in agriculture and as a flea controller in pets. Cotton, vegetables, and fruits are treated with indoxacarb, an insecticide that can be applied both indoors and outdoors. It causes skin allergies, methemoglobinemia, and hemolytic anemia. It is also attributed to allergic reactions through ingestion, inhalation, physical contact, and translaminar action. This case report highlights use of vitamin C in methemoglobinemia caused by indoxacarb poisoning. Indoxacarb poisoning has the potential to be extremely serious and even lethal. In this instance, the patient initially had no symptoms after ingesting a substance containing indoxacarb in an attempt at suicide. However, further tests revealed methemoglobinemia and low oxygen levels.

Case presentation

A 28-year-old south-east Asian female patient ingested an insecticide containing 5.25% novaluron, 4.5% indoxacarb, and 25% thiamethoxam, and reported that she noticed muddy brown urine but presented with no active signs or symptoms of poisoning. Upon examination, the patient was fully conscious, alert, and hemodynamically stable, but had an oxygen saturation of 84%. Gastric lavage was performed, and blood investigations revealed a muddy-brown-colored blood sample and methemoglobin levels of 12%. The patient was treated with high-dose vitamin C and showed significant improvement, with a drop in methemoglobin levels to 1.2% and an increase in oxygen saturation to 97%.

Discussion

Indoxacarb poisoning can cause severe methemoglobinemia. Vitamin C may be a useful treatment option for methemoglobinemia caused by indoxacarb, particularly in cases in which traditional treatment with methylene blue is contraindicated or not tolerated. Hence high doses of ascorbic acid, that is, vitamin C, were administered to the patient, which lowered their methemoglobin levels and improved oxygen levels without much safety concerns.

Conclusion

This example emphasizes the significance of early indoxacarb poisoning detection and treatment as well as the possible advantages of utilizing ascorbic acid in the management of methemoglobinemia, and highlights the use of vitamin C in the treatment of methemoglobinemia caused by indoxacarb poisoning. Therefore, it is important for healthcare professionals to be aware of the potential for indoxacarb to cause methemoglobinemia and to consider vitamin C as a treatment option.
CD4+ T cell count and HIV-1 viral load dynamics positively impacted by H. pylori infection in HIV-positive patients regardless of ART status in a high-burden setting
Authors: Abadi Tesfay , Teklu Takele , Wondmagegn Tadelo , Alem Meseret , Desalegn Girmay
Published: March 2024

Background

There is a widespread co-infection of HIV and Helicobacter pylori (H. pylori) globally, particularly in developing countries, and it has been suggested that this co-infection may affect the course of HIV disease. However, the interplay between H. pylori infection and HIV disease progression is not fully elucidated. In this study, we investigated the effect of H. pylori co-infection on CD4+ T cell count and HIV viral load dynamics in HIV-positive individuals in a high co-endemic setting.

Methods

A comparative cross-sectional study was conducted among 288 HIV-positive and 175 HIV-negative individuals, both with and without H. pylori infection. Among HIV-positive participants, 195 were on antiretroviral therapy (ART) and 93 were ART-naïve. CD4+ T cell count and HIV-1 viral load were measured and compared between H. pylori-infected and -uninfected individuals, taking into account different HIV and ART status.

Result

Our study demonstrated that individuals infected with H. pylori had a significantly higher CD4+ T cell count compared to uninfected controls among both HIV-negative and HIV-positive participants, regardless of ART therapy. Conversely, HIV/H. pylori co-infected participants had lower HIV-1 viral load than those without H. pylori infection. Linear regression analysis further confirmed a positive association between H. pylori infection, along with other clinical factors such as BMI, ART, and duration of therapy, with CD4+ T cell count while indicating an inverse relationship with HIV-1 viral load in HIV-positive patients. Additionally, factors such as khat chewing, age and WHO clinical stage of HIV were associated with reduced CD4+ T cell count and increased HIV-1 viral load.

Conclusion

Our study demonstrates that H. pylori co-infection was associated with higher CD4+ T cell count and lower HIV-1 viral load in HIV-positive patients, regardless of ART status. These findings show a positive effect of H. pylori co-infection on the dynamics of HIV-related immunological and virological parameters. Further studies are needed to elucidate the underlying mechanisms of the observed effects.
Construction of a gene model related to the prognosis of patients with gastric cancer receiving immunotherapy and exploration of COX7A1 gene function
Authors: Wang Si-yu , Wang Yu-xin , Shen Ao , Yang Xian-qi , Liang Cheng-cai , Huang Run-jie , Jian Rui , An Nan , Xiao Yu-long , Wang Li-shuai , Zhao Yin , Lin Chuan , Wang Chang-ping , Yuan Zhi-ping , Yuan Shu-qiang
Published: March 2024

Background

GC is a highly heterogeneous tumor with different responses to immunotherapy, and the positive response depends on the unique interaction between the tumor and the tumor microenvironment (TME). However, the currently available methods for prognostic prediction are not satisfactory. Therefore, this study aims to construct a novel model that integrates relevant gene sets to predict the clinical efficacy of immunotherapy and the prognosis of GC patients based on machine learning.

Methods

Seven GC datasets were collected from the Gene Expression Omnibus (GEO) database, The Cancer Genome Atlas (TCGA) database and literature sources. Based on the immunotherapy cohort, we first obtained a list of immunotherapy related genes through differential expression analysis. Then, Cox regression analysis was applied to divide these genes with prognostic significancy into protective and risky types. Then, the Single Sample Gene Set Enrichment Analysis (ssGSEA) algorithm was used to score the two categories of gene sets separately, and the scores differences between the two gene sets were used as the basis for constructing the prognostic model. Subsequently, Weighted Correlation Network Analysis (WGCNA) and Cytoscape were applied to further screen the gene sets of the constructed model, and finally COX7A1 was selected for the exploration and prediction of the relationship between the clinical efficacy of immunotherapy for GC. The correlation between COX7A1 and immune cell infiltration, drug sensitivity scoring, and immunohistochemical staining were performed to initially understand the potential role of COX7A1 in the development and progression of GC. Finally, the differential expression of COX7A1 was verified in those GC patients receiving immunotherapy.

Results

First, 47 protective genes and 408 risky genes were obtained, and the ssGSEA algorithm was applied for model construction, showing good prognostic discrimination ability. In addition, the patients with high model scores showed higher TMB and MSI levels, and lower tumor heterogeneity scores. Then, it is found that the COX7A1 expressions in GC tissues were significantly lower than those in their corresponding paracancerous tissues. Meanwhile, the patients with high COX7A1 expression showed higher probability of cancer invasion, worse clinical efficacy of immunotherapy, worse overall survival (OS) and worse disease-free survival (DFS).

Conclusions

The ssGSEA score we constructed can serve as a biomarker for GC patients and provide important guidance for individualized treatment. In addition, the COX7A1 gene can accurately distinguish the prognosis of GC patients and predict the clinical efficacy of immunotherapy for GC patients.
PDCL3 is a prognostic biomarker associated with immune infiltration in hepatocellular carcinoma
Authors: Jin Wenzhi , Wang Ganggang , Dong Meiyuan , Wang Xiaoliang
Published: March 2024

Background

Phosducin-like 3 (PDCL3) is a member of the photoreceptor family, characterized by a thioredoxin-like structural domain and evolutionary conservation. It plays roles in angiogenesis and apoptosis. Despite its significance, research on the biological role of PDCL3 in liver hepatocellular carcinoma (LIHC) remains limited. This study aims to explore the prognostic value and potential mechanisms of PDCL3 in cancer, particularly in LIHC, through bioinformatics analysis.

Methods

RNA-seq data and corresponding clinical information for pan-cancer and LIHC were extracted from the TCGA database to analyze PDCL3 expression and survival prognosis. Differential expression of PDCL3 was analyzed using the HPA database. GO and KEGG enrichment analysis were performed for PDCL3-associated genes. The relationship between PDCL3 expression and various immune cell types was examined using the TIMER website. Clinical samples were collected, and immunohistochemistry and immunofluorescence experiments were conducted to validate the differential expression of PDCL3 in LIHC and normal tissues. In vitro assays, including CCK-8, wound healing, Transwell, and colony formation experiments, were employed to determine the biological functions of PDCL3 in LIHC cells.

Results

Analysis from TIMER, GEPIA, UALCAN, and HPA databases revealed differential expression of PDCL3 in various tumors. Prognostic analysis from GEPIA and TCGA databases indicated that high PDCL3 expression was associated with poorer clinical staging and prognosis in LIHC. Enrichment analysis of PDCL3-associated genes revealed its involvement in various immune responses. TCGA and TIMER databases showed that high PDCL3 expression in LIHC decreased tumor immune activity by reducing macrophage infiltration. PDCL3 exhibited positive correlations with multiple immune checkpoint genes. Immunohistochemistry (IHC) and immunofluorescence (IF) experiments confirmed elevated PDCL3 expression in LIHC tissues compared to adjacent normal tissues. In vitro experiments demonstrated that PDCL3 promoted LIHC cell proliferation, migration, invasion, and colony-forming ability.

Conclusion

PDCL3 is highly expressed in various cancer types. Our study suggests that elevated PDCL3 expression in hepatocellular carcinoma is associated with poorer prognosis and may serve as a potential diagnostic biomarker for LIHC. PDCL3 may regulate the biological functions of LIHC by modulating immune infiltration. However, the precise regulatory mechanisms of PDCL3 in cancer warrant further investigation.
YME1L-mediated mitophagy protects renal tubular cells against cellular senescence under diabetic conditions
Authors: Luo Yuanyuan , Zhang Lingxiao , Su Ning , Liu Lerong , Zhao Tongfeng
Published: March 2024

Background

The senescence of renal tubular epithelial cells (RTECs) is crucial in the progression of diabetic kidney disease (DKD). Accumulating evidence suggests a close association between insufficient mitophagy and RTEC senescence. Yeast mitochondrial escape 1-like 1 (YME1L), an inner mitochondrial membrane metalloprotease, maintains mitochondrial integrity. Its functions in DKD remain unclear. Here, we investigated whether YME1L can prevent the progression of DKD by regulating mitophagy and cellular senescence.

Methods

We analyzed YME1L expression in renal tubules of DKD patients and mice, explored transcriptomic changes associated with YME1L overexpression in RTECs, and assessed its impact on RTEC senescence and renal dysfunction using an HFD/STZ-induced DKD mouse model. Tubule-specific overexpression of YME1L was achieved through the use of recombinant adeno-associated virus 2/9 (rAAV 2/9). We conducted both in vivo and in vitro experiments to evaluate the effects of YME1L overexpression on mitophagy and mitochondrial function. Furthermore, we performed LC–MS/MS analysis to identify potential protein interactions involving YME1L and elucidate the underlying mechanisms.

Results

Our findings revealed a significant decrease in YME1L expression in the renal tubules of DKD patients and mice. However, tubule-specific overexpression of YME1L significantly alleviated RTEC senescence and renal dysfunction in the HFD/STZ-induced DKD mouse model. Moreover, YME1L overexpression exhibited positive effects on enhancing mitophagy and improving mitochondrial function both in vivo and in vitro. Mechanistically, our LC–MS/MS analysis uncovered a crucial mitophagy receptor, BCL2-like 13 (BCL2L13), as an interacting partner of YME1L. Furthermore, YME1L was found to promote the phosphorylation of BCL2L13, highlighting its role in regulating mitophagy.

Conclusions

This study provides compelling evidence that YME1L plays a critical role in protecting RTECs from cellular senescence and impeding the progression of DKD. Overexpression of YME1L demonstrated significant therapeutic potential by ameliorating both RTEC senescence and renal dysfunction in the DKD mice. Moreover, our findings indicate that YME1L enhances mitophagy and improves mitochondrial function, potentially through its interaction with BCL2L13 and subsequent phosphorylation. These novel insights into the protective mechanisms of YME1L offer a promising strategy for developing therapies targeting DKD.
Nursing care of a 69-year-old patient after a stroke staying in the neurological ward
Authors: Ryś Bogusława , Gruszczyk Aneta
Published: March 2024

The presented work focuses on the description of issues related to ischemic stroke and the presentation of the patient's care process after this incident. The first part is a clinical description of the disease, and the second part is a case report of a patient after an ischemic stroke staying in a neurological ward.

The work also includes a description of the course of hospitalization, nursing problems, nursing interventions undertaken and evaluations of nursing activities.
Involvement in self-care of a patient with type 2 diabetes aged 60-80
Authors: Bąk Ewelina , Potoczna Renata , Kupczak-Wiśniowska Bogusława
Published: March 2024

Introduction: Self-care is an indispensable element of the treatment of type 2 diabetes, it involves the independent implementation of multidimensional activities that allow you to maintain proper glucose levels and reduce the risk of complications.

Materials and methods: The study was conducted on a group of 100 patients (including 56 women and 44 men) at the Health Clinic in Zembrzyce in the period from August 10, 2019 to October 30, 2019. The study was conducted using the diagnostic survey method. The research tools included: a self-report questionnaire consisting of a sociodemographic and clinical part and the Self-Care Inventory in Diabetes (SCODI).

Results: It was shown that greater independence in self-care regarding health behaviors, health control, glucose control and self-confidence were significantly higher in patients without addictions.

Conclusions: Involvement in self-care in the study population was higher among patients with secondary and higher education, and in patients without addictions, with normal body weight and underweight and treated with diet, tablets and insulin.
A Mixed-Methods Approach to Students’ Engagement in English Learning in the Chinese Context
Authors: Yang Xu , Liu Honggang
Published: March 2024

Since language use is at the center of language learning, learners’ active engagement in learning activities is crucial for successful language learning. Answering the call for positive language education, the present study investigated the levels and influencing factors of engagement in English learning among 437 Chinese senior high school students. This study employed an explanatory sequential mixed-methods design, collecting data through questionnaires and semi-structured interviews. The results showed that students were generally well-engaged in English learning. Moreover, students were more inclined to engage in English learning behaviorally, emotionally, and cognitively. Students’ agentic engagement in English learning was relatively low and mainly reflected after English classes. The relatively low agentic engagement might be shaped by a series of personal and contextual factors, including the traditional Chinese concept of “honoring and respecting the teacher”, teachers’ teaching strategies, students’ learning strategies, English proficiency, learning climate, and teaching styles. Pedagogical implications for English teachers concerning enhancing students’ English learning engagement were provided.
Using Motivational Strategies in a Business English Course: An English Teacher in the Context of English for Specific Purposes
Authors: Tsai Rumei Rebecca , Huang Shenghui Cindy
Published: March 2024

This study used a qualitative method to explore a teacher’s use of motivational strategies in an English for specific purposes (ESP) course and students’ perceptions. An English teacher in a business English class and her 32 students were recruited. The class was observed three times: at the beginning, in the middle, and at the end of the course. Two semi-structured interviews with the teacher were conducted: one before classroom observation, and the other after observation. Interviews with the students were conducted after each classroom observation. The teacher used seven motivational strategies to create a supportive and relaxed classroom atmosphere, and five strategies to facilitate students’ language learning. Most students’ perceptions of the teacher’s use of motivational strategies were positive. However, the students perceived a gap between their expectations for the course and their experiences. Finally, the article concludes by offering insights into the implications and constraints related to pedagogy.
Determinants of Grit in English Learning: A Qualitative Study on Vietnamese Students’ External and Internal Influences
Authors: Thao Le Thanh , Thuy Pham Trut , Chau Tran Ngoc Bao , Linh Nguyen Thi Thuy , Yen Phuong Hoang
Published: March 2024

This study delves into understanding the determinants of grit in English learning among Vietnamese students, highlighting both external and internal factors. Utilizing qualitative interviews, the research engaged with a cohort of 15 students, aiming to unearth the intricate interplay of influences that bolster their commitment and persistence in English studies. External factors emerged prominently, with teacher influence playing a significant role. Teachers’ motivational techniques, personalized feedback, and the establishment of a nurturing learning environment were underscored as pivotal in shaping students’ determination. On the internal facet, personal goals and aspirations, self-efficacy, intrinsic curiosity for the language, adaptive learning strategies, peer comparisons, and reflective self-assessment were identified as central elements. Insights from Constructivism and Socio-Cultural Theory were instrumental in interpreting the findings, revealing how individual experiences intersect with broader societal and cultural narratives. The study uncovered that while personal motivations and aspirations drive the students, they are simultaneously influenced by societal values, especially in the Vietnamese context, where education is deeply revered. This research contributes to the growing body of knowledge on grit in educational settings, shedding light on the unique cultural and individual determinants in the context of Vietnamese students learning English.
Cognitive Technology to Evaluate the Academic Learning of Computational Cognition in Psychology Students
Authors: Morales-Martinez Guadalupe Elizabeth , Garcia-Collantes Angel , Lopez-Perez Rafael Manuel
Published: March 2024

This study illustrated an alternative way to evaluate students’ academic learning. It involved the joint and intertwined application of the natural semantic network technique, computer simulations, and semantic priming experiments to assess the cognitive changes in knowledge structures due to academic learning in two groups of psychology students. The experimental group was enrolled in a course on computational cognition, while the control group was oblivious to this course. The results indicated that the cognitive assessment tools discriminate the cognitive changes produced as a result of general training undertaken in a psychology degree versus the influence of a specific course. After the course, the experimental group increased their technical vocabulary, changed their conceptual valuation of definers related to computational theories of mind, and reorganized the relations among definers according to the computational cognition approach. Also, this group presented a higher connectivity index between the concepts of the semantic network, their conceptual activation level and conceptual co-activation pattern changed, and their access level to the evaluated schema’s concepts improved. In contrast, the control group did not show significant changes in their cognitive patterns after the course. These findings suggest that cognitive tools may be helpful in the diagnosis of academic learning.
Empowering English as a Foreign Language Education With the Production-Oriented Approach: A Systematic Review
Authors: Liu Ying , Nasri Nurfaradilla Mohamad , Norman Helmi
Published: March 2024

The field of English as a Foreign Language (EFL) instruction has gained recognition worldwide, particularly in non-native English-speaking countries. However, traditional teaching methods fall short of meeting the needs of today's EFL learners. In response, the Production-Oriented Approach (POA) has emerged as a new pedagogical approach to address these challenges. Despite its significant impact on EFL education, there is a lack of reviews on the POA. This study conducted a systematic review to explore the POA's effectiveness, challenges, and future trends. Using the PRISMA framework, 31 articles from reputable databases (Web of Science, Education Resources Information Center, Scopus, and Google Scholar) were analyzed, covering the years 2018 to 2023. The study's comprehensive analysis, employing Nvivo, revealed that the POA has immense potential for enhancing English learners' language skills, particularly in reading, speaking, writing, and translating. Moreover, the study highlighted the POA's positive influence on learners' affective factors, including motivation, confidence, critical thinking, and self-directed learning abilities. Nonetheless, the POA faces challenges for both teachers and learners, particularly during the transition from traditional methods and the associated increase in workload. Despite these challenges, this study unequivocally establishes the POA as an effective pedagogical approach for teaching EFL. Additionally, it identifies research gaps that must be addressed to sustain and improve EFL education in the future through further development of the POA.