bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum insulin-like growth factor-1 as a potential prognostic biomarker for heart failure with reduced ejection fraction: a meta-analysis
Authors: Liu Tingting , Li Fangyu , Fei Yihuan , Sun Fangling , Chen Mengqi , Tian Xin , Zheng Wenrong , Zhu Zixin , Wang Wen
Published: September 2024

Background

Most studies have indicated that peripheral insulin-like growth levels factor-1 (IGF-1) is valuable in diagnosing heart failure, although the results have been inconsistent. To help solve the debate, we performed a meta-analysis to explore the relationship between IGF-1 and heart failure (HF).

Methods

We conducted an extensive search across various databases such as Embase, Cochrane Library, Pubmed, Medline, and Web of Science on May 30, 2023. From the extensive pool of studies, we selected 16 relevant articles, encompassing a total of 1,380 cases and 1,153 controls, to conduct a rigorous meta-analysis.

Results

The total results indicated that there is an association between lower IGF-1 level and HF. The random-effects model yielded a pooled standardized mean difference (SMD) of −0.598 (95% CI: −1.081 to −0.116, P = 0.015). Further subgroup analysis also showed that IGF-1 levels were associated with HF in the age difference ≥5 years subgroup and body mass index difference >1 subgroup. Additionally, significant association between IGF-1 levels and HF were detected in the “serum” samples and “Europe” subgroups. Importantly, we observed IGF-1 showed significant lower levels in patients with reduced ejection fraction (HFrEF) compared to the controls, not in patients with preserved ejection fraction (HFpEF). The Begg’s and Egger’s tests revealed no indication of publication bias.

Conclusions

Our meta-analysis has provided evidence suggesting a substantial correlation between reduced levels of IGF-1 and the occurrence of HF. Further prospective studies are necessary to ascertain the use of IGF-1 as a reliable biomarker for diagnosing HF, especially for HFrEF. But the diagnosis of HFpEF should be cautious.
Challenges in the management of familial hypercholesterolemia: a case report
Authors: Rogozik Joanna , Grabowski Marcin , Główczyńska Renata
Published: September 2024

Background

Familial hypercholesterolemia (FH) is a serious genetic condition that results in abnormally high levels of low-density lipoprotein cholesterol (LDL-C) in the bloodstream, significantly increasing the risk of early onset of cardiovascular disease. The heterozygous form of FH (HeFH) is widespread, affecting around 1 in 500 people worldwide.

Case report

In this clinical report, we present the case of a patient who suffers from HeFH due to a mutation in the LDL receptor (LDLR) gene. A woman exhibited intolerance to statin therapy and did not attain adequate reduction in low-density lipoprotein cholesterol (LDL-C) levels on ezetimibe monotherapy. Genetic testing confirmed the presence of a pathogenic variant for FH with the deletion of exons 7–14. The administration of alirocumab (a dose of 150 mg sc) as the primary therapy did not exhibit the desired therapeutic outcome. Consequently, the patient was given inclisiran therapy (a dose of 284 mg sc), which significantly reduced LDL cholesterol levels after 3 months of treatment and during the 1-year follow-up.

Conclusion

Inclisiran therapy has shown promising results for individuals with HeFH who experience statin intolerance. This therapy works by using a small interfering RNA (siRNA) to target the mRNA of proprotein convertase subtilisin/kexin type 9 (PCSK9), which leads to a significant reduction of LDL-C levels. This approach can be an alternative for patients without significant reductions in LDL-C levels with PCSK9 inhibitor therapy. For HeFH patients with limited treatment options due to statin intolerance and genetic mutations, inclisiran can represent a promising therapeutic option.
Analyses of non-native Estonian, Latvian, and Swedish young learners’ written production in EFL: similarities and differences
Authors: Sundh Stellan
Published: September 2024

Assessments of written production in English as a foreign language play an important role in the overall grading of learners’ English at school. Evidently, the other three skills than writing are also considered, but written texts are useful to work with as they provide concrete material easily available to study when it comes to learners’ levels of achieved language proficiency. The teachers’ overall and immediate impression of the text could play a significant role in the final grading of the production. It is therefore worth investigating the variation of linguistic features in texts of similar length produced by learners of the same age. In the present study, young learners’ written production in English is analyzed with several approaches. The learners’ texts were of similar length and language quality but had different characteristics in terms of structure and style. The results show an overall picture of factors influencing teachers’ assessment of young learners’ texts in EFL and are therefore useful information to consider for English teachers to ensure valid and reliable assessments of learners’ written productions of English as a foreign language.
Perceptions of special education pre-service teachers regarding the implementation of a neuroscience motifs-based teacher training program
Authors: Luzzatto Efrat , Shalom Maya , Rusu Alina S.
Published: September 2024

While the interest in the connection between neuroscience and education continues to increase, there is a gap between the declarative statements regarding its importance and the small number of programs that put it into practice. The perceptions of the participants in these programs might offer valuable insights regarding the applied values of this connection. This study seeks to contribute to the accumulated research knowledge by using a qualitative analysis approach regarding the perceptions of pre-service teachers (PSTs) in a special education track program. The PSTs participated in a unique training program called the “Neuroscience Motifs-based Teacher Training Program” (NMTTP) that was presented as part of a reading course. Findings reveal mostly positive perceptions of the PSTs regarding the importance, relevance and contribution of neuroeducation to education, from a professional & personal perspective. In addition, the findings expand the current literature in two aspects: (1) the potential benefits that neuroscience can grant to education in general, and to special education in particular; (2) the contribution of knowledge on neural basis for PSTs to a sense of perspective, patience and empathy toward challenging students, by understanding some of the ongoing processes in their students’ brains.
New challenges for higher education: self-regulated learning in blended learning contexts
Authors: Lobos Karla , Cobo-Rendón Rubia , Bruna Jofré Daniela , Santana Javiera
Published: September 2024

Introduction

The study on self-regulated learning in blended learning (BL) environments highlights its crucial relevance for both the academic development of students and the evolution of contemporary educational methods. This research focused on conceptualizing self-regulated learning in university contexts with a BL modality, using direct student perceptions.

Methods

An inductive qualitative approach with a phenomenological design was employed. Responses from 312 undergraduate students who had completed their first or second year were analyzed; 65 participated in 10 focus groups (two per area of knowledge according to OECD classification), and 247 participated through a survey. Descriptive analysis was used to obtain a range of content and meanings associated with students’ perceptions of SRL-BL.

Results

The study conceptualized SRL-BL as a process where students structure, monitor, and evaluate their learning using self-reflection and digital technologies, with particular emphasis on planning. Significant differences were identified between SRL-BL and traditional SRL; in face-to-face education, teacher supervision is greater, while in SRL-BL, students take on more responsibility and autonomy, developing self-management skills. Although SRL-BL fosters autonomy and responsibility, students face obstacles such as distractions from social media and leisure technologies, which affect their concentration and study planning.

Discussion

It is essential to address the new challenges students face to maintain a high level of SRL in Blended Learning environments (SRL-BL) and the strategies they use to overcome them. The need to update the concept of self-regulated learning (SRL) in the current educational context, influenced by technological advances, is concluded.
Rethinking of phosphodiesterase 5 inhibition: the old, the new and the perspective in human health
Authors: Paronetto Maria Paola , Crescioli Clara
Published: September 2024

The phosphodiesterases type 5 (PDE5) are catalytic enzymes converting the second messenger cyclic guanosine monophosphate (cGMP) to 5’ GMP. While intracellular cGMP reduction is associated with several detrimental effects, cGMP stabilization associates with numerous benefits. The PDE5 specific inhibitors, PDE5i, found their explosive fortune as first-line treatment for erectile dysfunction (ED), due to their powerful vasoactive properties. The favorable effect for ED emerged as side-effect when PDE5i were originally proposed for coronary artery disease (CAD). From that point on, the use of PDE5i captured the attention of researchers, clinicians, and companies. Indeed, PDE5-induced intracellular cGMP stabilization offers a range of therapeutic opportunities associated not only with vasoactive effects, but also with immune regulatory/anti-inflammatory actions. Chronic inflammation is acknowledged as the common link underlying most non-communicable diseases, including metabolic and cardiac diseases, autoimmune and neurodegenerative disorders, cancer. In this scenario, the clinical exploitation of PDE5i is undeniably beyond ED, representing a potential therapeutic tool in several human diseases. This review aims to overview the biological actions exerted by PDE5i, focusing on their ability as modulators of inflammation-related human diseases, with particular attention to inflammatory-related disorders, like cardiac diseases and cancer.
Long-term trends in water transparency of Tibetan Plateau lakes and the response to extreme climate events
Authors: Liu Wangming , Xu Huan , He Guowei
Published: September 2024

Water transparency, as indicated by the Secchi disk depth (Zsd), is a key parameter for assessing the quality of aquatic environments, reflecting the ability of light to penetrate through the water column. In the Tibetan Plateau (TP), where lakes are abundant yet remote and challenging to access, remote sensing techniques offer a promising approach for monitoring Zsd over large spatial scales. In this study, we used the semianalytical -based Zsd algorithm to study the temporal and spatial dynamics of water transparency over TP during the period from 2003 to 2022. The results show that the 173 lakes have a mean value of Zsd is 3.64 ± 2.4 m for long term, and generally with the significantly increasing change trends in the past 20 years. In the central Tibetan Plateau (CTP) region, lake transparency showed a positive correlation with lake surface temperature (r = 0.73) and a negative correlation with precipitation (r = −0.54), highlighting the region’s heightened sensitivity to meteorological changes compared to other areas. The spike in water clarity observed in the CTP region may be linked to alterations in lake hydrodynamics driven by the extremely climate events (i.e., El Niño). These results indicated the importance of considering regional climatic factors when interpreting fluctuations in water transparency.
Dementia risk prediction modelling in low- and middle-income countries: current state of evidence
Authors: Alshahrani Maha , Sabatini Serena , Mohan Devi , Brain Jacob , Pakpahan Eduwin , Tang Eugene Y. H. , Robinson Louise , Siervo Mario , Naheed Aliya , Stephan Blossom Christa Maree
Published: September 2024

Dementia is a leading cause of death and disability with over 60% of cases residing in low- and middle-income countries (LMICs). Therefore, new strategies to mitigate risk are urgently needed. However, despite the high burden of disease associated with dementia in LMICs, research into dementia risk profiling and risk prediction modelling is limited. Further, dementia risk prediction models developed in high income countries generally do not transport well to LMICs suggesting that context-specific models are instead needed. New prediction models have been developed, in China and Mexico only, with varying predictive accuracy. However, none has been externally validated or incorporated variables that may be important for predicting dementia risk in LMIC settings such as socio-economic status, literacy, healthcare access, nutrition, stress, pollutants, and occupational hazards. Since there is not yet any curative treatment for dementia, developing a context-specific dementia prediction model is urgently needed for planning early interventions for vulnerable groups, particularly for resource constrained LMIC settings.
Immune response to viscerotropic Leishmania: a comprehensive review
Authors: Lodi Lorenzo , Voarino Marta , Stocco Silvia , Ricci Silvia , Azzari Chiara , Galli Luisa , Chiappini Elena
Published: September 2024

L. donovani and L. infantum infections are associated with a broad clinical spectrum, ranging from asymptomatic cases to visceral leishmaniasis (VL) with high mortality rates. Clinical manifestations such as post-kala-azar dermal leishmaniasis (PKDL) and visceral leishmaniasis-associated hemophagocytic lymphohistiocytosis-mimic (VL-associated HLH-mimic) further contribute to the diversity of clinical manifestations. These clinical variations are intricately influenced by the complex interplay between the host’s immune response and the parasite’s escape mechanisms. This narrative review aims to elucidate the underlying immunological mechanisms associated with each clinical manifestation, drawing from published literature within the last 5 years. Specific attention is directed toward viscerotropic Leishmania sinfection in patients with inborn errors of immunity and acquired immunodeficiencies. In VL, parasites exploit various immune evasion mechanisms, including immune checkpoints, leading to a predominantly anti-inflammatory environment that favors parasite survival. Conversely, nearly 70% of individuals are capable of mounting an effective pro-inflammatory immune response, forming granulomas that contain the parasites. Despite this, some patients may experience reactivation of the disease upon immunosuppression, challenging current understandings of parasite eradication. Individuals living with HIV and those with inborn errors of immunity present a more severe course of infection, often with higher relapse rates. Therefore, it is crucial to exclude both primary and acquired immune deficiencies in patients presenting disease relapse and VL-associated HLH-mimic. The distinction between VL and HLH can be challenging due to clinical similarities, suggesting that the nosological entity known as VL-associated HLH may represent a severe presentation of symptomatic VL and it should be considered more accurate referring to this condition as VL-associated HLH-mimic. Consequently, excluding VL in patients presenting with HLH is essential, as appropriate antimicrobial therapy can reverse immune dysregulation. A comprehensive understanding of the immune-host interaction underlying Leishmania infection is crucial for formulating effective treatment and preventive strategies to mitigate the disease burden.
Variation within the non-coding genome influences genetic and epigenetic regulation of the human leukocyte antigen genes
Authors: Arumugam Thilona , Adimulam Theolan , Gokul Anmol , Ramsuran Veron
Published: September 2024

Variation within the non-coding genome may influence the regulation and expression of important genes involved in immune control such as the human leukocyte antigen (HLA) system. Class I and Class II HLA molecules are essential for peptide presentation which is required for T lymphocyte activation. Single nucleotide polymorphisms within non-coding regions of HLA Class I and Class II genes may influence the expression of these genes by affecting the binding of transcription factors and chromatin modeling molecules. Furthermore, an interplay between genetic and epigenetic factors may also influence HLA expression. Epigenetic factors such as DNA methylation and non-coding RNA, regulate gene expression without changing the DNA sequence. However, genetic variation may promote or allow genes to escape regulation by epigenetic factors, resulting in altered expression. The HLA system is central to most diseases, therefore, understanding the role of genetics and epigenetics on HLA regulation will tremendously impact healthcare. The knowledge gained from these studies may lead to novel and cost-effective diagnostic approaches and therapeutic interventions. This review discusses the role of non-coding variants on HLA regulation. Furthermore, we discuss the interplay between genetic and epigenetic factors on the regulation of HLA by evaluating literature based on polymorphisms within DNA methylation and miRNA regulatory sites within class I and Class II HLA genes. We also provide insight into the importance of the HLA non-coding genome on disease, discuss ethnic-specific differences across the HLA region and provide guidelines for future HLA studies.
Immune-Mediated Inflammatory Diseases and Cancer - a dangerous liaison
Authors: Maier Jeanette A. , Castiglioni Sara , Petrelli Alessandra , Cannatelli Rosanna , Ferretti Francesca , Pellegrino Greta , Sarzi Puttini Piercarlo , Fiorina Paolo , Ardizzone Sandro
Published: September 2024

Patients with Immune-Mediated Inflammatory Diseases (IMIDs) are known to have an elevated risk of developing cancer, but the exact causative factors remain subject to ongoing debate. This narrative review aims to present the available evidence concerning the intricate relationship between these two conditions. Environmental influences and genetic predisposition lead to a dysregulated immune response resulting in chronic inflammation, which is crucial in the pathogenesis of IMIDs and oncogenic processes. Mechanisms such as the inflammatory microenvironment, aberrant intercellular communication due to abnormal cytokine levels, excessive reparative responses, and pathological angiogenesis are involved. The chronic immunosuppression resulting from IMIDs treatments further adds to the complexity of the pathogenic scenario. In conclusion, this review highlights critical gaps in the current literature, suggesting potential avenues for future research. The intricate interplay between IMIDs and cancer necessitates more investigation to deepen our understanding and improve patient management.
Circulating immune cells and apolipoprotein A mediation: a Mendelian randomization study on hypertensive disorder of pregnancy
Authors: Liu Jingting , Zhou Yawei , Dong Yijun , Wang Wendi , Li Yan , Pei Jianying
Published: September 2024

Background

Studies using observational epidemiology have indicated that inflammation and immunological dysregulation are important contributors to placental and renal failure, which ultimately results in maternal hypertension. The potential causal relationships between the immunophenotypes and hypertensive disorder of pregnancy (HDP) are yet unclear.

Methods

We conducted two-sample Mendelian randomization (MR) analyses to thoroughly examine the relationship between immunophenotypes and HDP. The GWAS data on immunological traits was taken from public catalog for 731 immunophenotypes and the summarized GWAS data in 4 types of HDP were retrieved from FinnGen database. The link between immune cell traits and HDP was examined through our study methodology, taking into account both direct relationships and mediation effects of apolipoprotein A (apoA). The inverse variance weighted (IVW) method served as the main analysis, while sensitivity analysis was carried out as a supplement.

Results

We identified 14 highly correlative immunophenotypes and 104 suggestive possible factors after investigating genetically predicted immunophenotype biomarkers. According to the IVW analysis, there was a strong correlation between HDP and HLA DR on DC and plasmacytoid DC. Reverse MR analysis showed that there was no statistically significant effect of HDP on immune cells in our investigation. Mediation analysis confirmed that apoA mediates the interaction between HLA DR on DC and HDP.

Conclusion

Our results highlight the complex interplay of immunophenotypes, apoA, and HDP. Moreover, the pathophysiological link between HLA DR on DC and HDP was mediated by the level of apoA.
A clinical protocol for a German birth cohort study of the Maturation of Immunity Against respiratory viral Infections (MIAI)
Authors: Hartmann Carina R. , Khan Robin , Schöning Jennifer , Richter Maximilian , Willers Maike , Pirr Sabine , Heckmann Julia , Dirks Johannes , Morbach Henner , Konrad Monika , Fries Elena , Winkler Magdalene , Büchel Johanna , Seidenspinner Silvia , Fischer Jonas , Vollmuth Claudia , Meinhardt Martin , Marissen Janina , Schmolke Mirco , Haid Sibylle , Pietschmann Thomas , Backes Simone , Dölken Lars , Löber Ulrike , Keil Thomas , Heuschmann Peter U. , Wöckel Achim , Sagar  , Ulas Thomas , Forslund-Startceva Sofia K. , Härtel Christoph , Viemann Dorothee
Published: September 2024

Introduction

Respiratory viral infections (RVIs) are a major global contributor to morbidity and mortality. The susceptibility and outcome of RVIs are strongly age-dependent and show considerable inter-population differences, pointing to genetically and/or environmentally driven developmental variability. The factors determining the age-dependency and shaping the age-related changes of human anti-RVI immunity after birth are still elusive.

Methods

We are conducting a prospective birth cohort study aiming at identifying endogenous and environmental factors associated with the susceptibility to RVIs and their impact on cellular and humoral immune responses against the influenza A virus (IAV), respiratory syncytial virus (RSV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The MIAI birth cohort enrolls healthy, full-term neonates born at the University Hospital Würzburg, Germany, with follow-up at four defined time-points during the first year of life. At each study visit, clinical metadata including diet, lifestyle, sociodemographic information, and physical examinations, are collected along with extensive biomaterial sampling. Biomaterials are used to generate comprehensive, integrated multi-omics datasets including transcriptomic, epigenomic, proteomic, metabolomic and microbiomic methods.

Discussion

The results are expected to capture a holistic picture of the variability of immune trajectories with a focus on cellular and humoral key players involved in the defense of RVIs and the impact of host and environmental factors thereon. Thereby, MIAI aims at providing insights that allow unraveling molecular mechanisms that can be targeted to promote the development of competent anti-RVI immunity in early life and prevent severe RVIs.

Clinical trial registration

https://drks.de/search/de/trial/, identifier DRKS00034278.
SARS-CoV-2 spike protein induces the cytokine release syndrome by stimulating T cells to produce more IL-2
Authors: Niu Chao , Liang Tingting , Chen Yongchong , Zhu Shan , Zhou Lei , Chen Naifei , Qian Lei , Wang Yufeng , Li Min , Zhou Xin , Cui Jiuwei
Published: September 2024

Introduction

Cytokine release syndrome (CRS) is one of the leading causes of mortality in patients with COVID-19 caused by the SARS-CoV-2 coronavirus. However, the mechanism of CRS induced by SARS-CoV-2 is vague.

Methods

Using spike protein combined with IL-2, IFN-γ, and TNF-α to stimulate human peripheral blood mononuclear cells (PBMCs) to secrete CRS-related cytokines, the content of cytokines in the supernatant was detected, and the effects of NK, T, and monocytes were analyzed.

Results

This study shows that dendritic cells loaded with spike protein of SARS-CoV-2 stimulate T cells to release much more interleukin-2 (IL-2,) which subsequently cooperates with spike protein to facilitate PBMCs to release IL-1β, IL-6, and IL-8. These effects are achieved via IL-2 stimulation of NK cells to release tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), as well as T cells to release IFN-γ Mechanistically, IFN-γ and TNF-α enhance the transcription of CD40, and the interaction of CD40 and its ligand stabilizes the membrane expression of toll-like receptor 4 (TLR4) that serves as a receptor of spike protein on the surface of monocytes. As a result, there is a constant interaction between spike protein and TLR4, leading to continuous activation of nuclear factor-κ-gene binding (NF-κB). Furthermore, TNF-α also activates NF-κB signaling in monocytes, which further cooperates with IFN-γ and spike protein to modulate NF-κB–dependent transcription of CRS-related inflammatory cytokines.

Discussion

Targeting TNF-α/IFN-γ in combination with TLR4 may represent a promising therapeutic approach for alleviating CRS in individuals with COVID-19.
Identifying immune checkpoints on dysregulated T-cells as prognostic biomarkers for multiple myeloma patients with COVID-19
Authors: Li Ziping , He Huiwen , Zhang Fujing , Li Haolong , Jin Xianghong , Song Yuhang , Liu Shuangjiao , Wang Xuan , Zhuang Junling
Published: September 2024

Background

Broad T cell phenotypic alterations and potential dysfunctions were prominent in COVID-19. There are few and inconclusive data about the role of immune checkpoints for T cell exhaustion/activation during SARS-CoV-2 infection in multiple myeloma (MM) patients.

Methods

We tested T cell subsets and immune checkpoints in 177 MM patients with COVID-19, as well as in 32 healthy infected controls and 42 uninfected MM patients. The percentage of CD4+ and CD8+ subpopulation and immune checkpoints (PD-1, TIGIT, TIM-3, LAG-3, CTLA-4, OX40, and 4-1BB) were evaluated by flow cytometry.

Results

We have found that pronounced lymphopenia and inverted CD4/CD8 ratio in severe COVID-19 patients were especially developed within the first month after infection. And T cell subset dysregulation was persistent in severe patients recovering from SARS-CoV-2 infection. Immune checkpoints on CD4+ T cells were variable and uncorrelated with the level of adaptive immunity, while the proportion of CD4+ T cells was positively correlated with humoral immune response. PD-1 and TIGIT on CD8+ T cells were significantly elevated in severe patients and sustained for more than 2 months, which was associated with impaired cellular immune function. Moreover, exhausted molecules PD-1 and TIGIT on T cells were reduced in immunotherapy patients.

Conclusion

The prolonged T cell dysregulation after severe SARS-CoV-2 infection highlights the close surveillance from reinfection in MM patients even during convalescence. PD-1 and TIGIT on CD8+ T cells could be important prognostic factors to stratify prognosis in MM patients with COVID-19. Moreover, immunotherapy may downregulate the expression of exhausted checkpoints PD-1 and TIGIT, leading to T cell overactivation and severe COVID-19.
Case report: Successful combination of CLL1 CAR-T therapy and hematopoietic stem cell transplantation in a 73-year-old patient diagnosed with refractory acute myeloid leukemia
Authors: Zhao Yifan , Wang Hao , Zhang Yu , Zhang Yi , Zhang Xiaomei , Zhao Mohan , Liu Jile , Guo Shujing , Zhao Mingfeng
Published: September 2024

The incidence of Acute myeloid leukemia (AML) increases with advancing age, and the prognosis for elderly patients is significantly poorer compared to younger patients. Although the combination therapy of venetoclax and hypomethylating agents has demonstrated improved prognosis in patients unable to tolerate intensive chemotherapy, there remains a therapeutic blank for those who fail to achieve remission with current treatment regimens. Here, we report the successful clinical utilization of autogenous CLL1 CAR-T therapy combined with hematopoietic stem cell transplantation in a 73-year-old patient diagnosed with refractory AML. The patient achieved morphological complete remission (CR) with incomplete marrow recovery and a slight presence of minimal residual disease (MRD) after receiving CLL1 CAR-T therapy. To further enhance the treatment and promote the recovery of hemopoiesis, we performed bridged allogenic hematopoietic stem cell transplantation (allo-HSCT) 20 days after the infusion of CLL1 CAR-T cells. The patient achieved MRD-negative CR following HSCT treatment. His primary disease maintained a complete remission status during the 11-month follow-up period. The patient encountered grade 2 cytokine release syndrome and grade 4 granulocytopenia subsequent to the infusion of CAR-T cells, while several rounds of infection and graft-versus-host disease were observed following allo-HSCT. Nevertheless, all these concerns were successfully addressed through comprehensive provision of supportive treatments. We have successfully demonstrated a highly effective and safe combination strategy involving CLL1 CAR-T therapy and allo-HSCT, which has exhibited remarkable tolerability and holds great promise even for elderly patients with AML.
Abundance and diversity of cotton insect pests under repeatedly cultivated cotton fields of Tanzania
Authors: Benjamin Madama , Rwegasira Gration M.
Published: September 2024

Introduction

Cotton production in Tanzania is facing significant challenges due to insect pests that cause extensive damages to the crop. The most notable pests include the African bollworm (Heliothis armigera Hubner), Spiny bollworm (Earias biplaga Walker), Cotton stainers (Dysdercus sidae (Herrich-Schaeffer), Cotton Aphids (Aphis gossypii Glover), Thrips (Thrips tabaci Lindeman), Jassids (Amrasca biguttula, Bigutula), Leafhoppers (Cicadellidae jassidae), and Whiteflies (Bemisia tabaci Genn). If left uncontrolled, these pests can cause up to 60% damage to the crop. Despite the importance of cotton and the fact that most of these pests are endemic, there are scanty knowledge on the dynamics and distribution of cotton pests across the seasons of the year and crop’s phenological growth stages (germination, vegetative growth, flowering and boll formation) in areas under repeated cultivation of the crop in Tanzania. Here we report on the influence of seasons and cotton’s phenological stages on the abundance, diversity, distribution and richness of cotton insect pests.

Methods

The study was conducted in the Misungwi district for two cotton-growing seasons, using the UKM08 cotton variety. Stick traps and handpicking methods were deployed in catching the cotton insect pests.

Results

On average, a total of 8,500 insect specimen of diverse families and species were collected every season. The four dominant species among the collected were Aphis gossypii (17.37%), Amrasca biguttula (11.42%), Nezara viridura (10.7%), and Bemisia tabacci (10.68%). Both cotton phenological growth stages and seasons significantly (p<0.05) influenced the abundance, diversity, distribution and richness of cotton insect pests. In particular, the phenological growth stage 3 exhibited greater diversity of insect pests. The pests’ distribution patterns remained relatively uniform across the crop growth stages.

Discussion

Findings from the present study could contribute to developing sustainable pest management strategies in areas under repeated cotton production in Tanzania and elsewhere.
Potential uses of silkworm pupae (Bombyx mori L.) in food, feed, and other industries: a systematic review
Authors: Rodríguez-Ortiz Luis Miguel , Hincapié Carlos A. , Hincapié-Llanos Gustavo Adolfo , Osorio Marisol
Published: September 2024

The increasing pressures imposed on ecosystems by the growing needs of the human population are stimulus for research into innovative and unconventional sources of raw materials for different industries. This systematic review was carried out to investigate the available literature on the possible industrial uses of silkworm (Bombyx mori L.) pupae, a residue of silk production. The review was conducted using an adapted version of PRISMA. After a screening process, 105 articles were obtained and subjected to a detailed quantitative and qualitative analysis. It was found that in the last decade there has been a significant increase in the number of papers devoted to the study of the potential use of silkworm pupae in different applications, with a significantly higher number in the last three years of the scope of this review, indicating a growing interest in the subject. From the analysis of the information collected, promising uses in human and animal food, such as fish, mammalian, poultry, swine and companion animals, as well as potential uses for the pharmaceutical industry, were identified. The evaluated research identified compounds with antioxidant activity and important contents of unsaturated fatty acids, which are related to beneficial effects on cardiovascular health, diabetes control, reduction of the risk of developing certain types of cancer and inflammatory activity, among other benefits. One of the most relevant findings is that many studies report a significant concentration of α-linolenic acid in silkworm pupae oil, which is attributed with anticancer, anti-inflammatory, antioxidant, anti-obesity and neuroprotective properties, among others.
Circadian migrations of cave-dwelling crustaceans guided by their home chemical seascape
Authors: Derrien Marie , Santonja Mathieu , Greff Stéphane , Figueres Soizic , Simmler Charlotte , Chevaldonné Pierre , Pérez Thierry
Published: September 2024

Organisms release and detect molecules for defense, reproduction, feeding strategies and finding suitable habitats. For some migratory species, homing behavior could be related to the recognition of their home chemical fingerprint made of an assemblage of molecules from their habitat. In the marine realm, the functioning of ecosystems such as underwater caves largely depends on trophic interactions between the caves and the outside environment. A key feature of these interactions relies on the circadian migration of small crustaceans (Mysida) from the cave habitat to the open sea. Recently, it has been hypothesized that these migrations could involve chemical mediation. Behavioral experiments using a two-choice system have shown that cave mysids significantly detect cave seawater rather than a control water from the open sea. Here, we used the same experimental system to investigate habitat recognition by two populations of the cave mysid Hemimysis margalefi. Both populations were submitted to a choice between three distinct cave seawaters vs. a control seawater. Additionally, experiments tested the water preference of a non-cave mysid species (Leptomysis sp.) between control and cave seawaters. To evaluate whether the choice of mysids was influenced by chemical cues from conspecifics, a complementary experiment on H. margalefi was conducted. Results demonstrated that each studied mysids population significantly recognizes the water of its own home habitat, and that this behavior is not influenced by the occurrence of H. margalefi’s exudates. Mass spectrometry-based metabolomic analyses revealed that each cave seawater had a specific chemical fingerprint with only a few reproducibly detected signals belonging to different chemical classes: peptides, alkaloids, fatty acids, steroids but also inorganic molecules. Organic pollutants have also been reproducibly detected. Among the detected compounds, one oxylipin derivative and one peptide could be considered as chemical markers of the cave ecosystem. Therefore, we postulate that the chemical seascape of each cave participates to mysid circadian migrations which are analogous to a daily-based homing behavior.
Interpretable machine learning for understanding compositional and testing condition effects on refractive index, density, dielectric constant, and loss tangent of inorganic melts and glasses
Authors: Zaki Mohd , Jayadeva  , Krishnan N. M. Anoop
Published: September 2024

Artificial intelligence (AI) and machine learning (ML) have enabled property-targeted design of glasses. Several machine learning models and open-source tools in the literature allow researchers to predict the optical, physical, mechanical, and electrical properties of glasses as a function of their chemical compositions. However, these properties also depend on testing conditions. In this paper, we train machine learning models by considering composition and wavelength, temperature, and frequency to predict the refractive index, density, and the two electrical properties, i.e., dielectric constant and loss tangent of glasses, respectively. The predictions of trained models are explained using SHAP analysis, revealing that testing conditions, such as wavelength and temperature, interact majorly with network formers while predicting refractive index and density. In the case of electrical properties, network formers and frequency have the highest interactions, followed by network modifiers and intermediates, and hence govern predictions of dielectric constant and loss tangent. Overall, AI/ML models that can predict the properties of glasses as a function of their composition and testing conditions, coupled with SHAP plots, provide a practical tool to develop a range of glasses for application under varying conditions.
Dry eye disease and spondyloarthritis: expanding the spectrum of systemic inflammatory disorders associated with ocular surface disease. Data from the international AIDA Network Spondyloarthritis Registry
Authors: Vitale Antonio , Caggiano Valeria , Martín-Nares Eduardo , Di Meglio Nunzia , Sica Cristian , Hinojosa-Azaola Andrea , Perfetti Maria Orsetta , Pagliara Alessandra , Guidetti Giorgia , Fonollosa Alex , Lopez Roberta , Sbalchiero Jessica , Sota Jurgen , Carreño Ester , Kawakami-Campos Perla Ayumi , Gentileschi Stefano , de-la-Torre Alejandra , Tosi Gian Marco , Mazzei Maria Antonietta , Balistreri Alberto , Frediani Bruno , Cantarini Luca , Fabiani Claudia
Published: September 2024

Objective

Dry eye disease (DED) is a condition associated with a myriad of systemic disorders. According to recent preliminary data, axial spondylarthritis (axial-SpA) could represent a new entity associated with DED. Therefore, this study aimed to assess DED in patients with axial SpA by performing quantitative and qualitative specific tests to investigate the potential association between DED and ocular surface damage in patients with axial-SpA and to identify potential variables associated with DED.

Methods

A total of 71 patients with axial-SpA who fulfilled the Assessment of SpondyloArthritis International Society (ASAS) classification criteria and 19 healthy controls were enrolled in this study. Both the patients and the controls underwent a complete ocular assessment aimed at evaluating the tear film and ocular surface, which included the Schirmer test, tear break-up time (TBUT), fluorescein staining, and lissamine green staining. The Ocular Surface Disease Index (OSDI) questionnaire was administered to all patients.

Results

DED symptoms were reported in 46 (64.8%) patients and three (15.8%) healthy controls (p = 0.0004). The odds ratio for receiving a diagnosis of axial-SpA based on the presence of dry-eye-related symptoms was 9.2 (95% C.I. 2.72–42.52, p = 0.001). The Schirmer test values of < 6 mm/5 min were observed in 31 (43.7%) patients with axial-SpA and two (10.5%) healthy controls (p = 0.013); a TBUT of <5 s was observed in 34 (47.9%) patients with axial-SpA and six (31.6%) healthy controls. The median OSDI score was found to be 22.9 (IQR = 29.35) among the patients with axial-SpA and 0.0 (IQR = 4.69) among the healthy controls (p = 0.009). The fluorescein and lissamine green staining of the ocular surface indicated a significantly higher Oxford Grading Scale in the patients with axial-SpA than in the healthy controls.

Conclusion

Patients with axial-SpA often complain of eye dryness, which may be quantified with the self-administered OSDI questionnaire and objectively assessed through the tests commonly used for the diagnosis of DED. Patients suspected of having axial-SpA should routinely be asked about dry eye symptoms and evaluated for potential corneal and conjunctival damage.
Vulnerability, social value and the equitable sharing of benefits from research: beyond the placebo and access debates
Authors: Kurihara Chieko , Greco Dirceu , Dhai Ames , Matsuyama Kotone , Baroutsou Varvara
Published: September 2024

The vulnerability of research participants is a critical topic for the 2024 revision of the Declaration of Helsinki, with the proposal to include “social value. ” However, this proposal has been withdrawn and the relationship between the two concepts has not been clarified. This paper attempts to clarify: (1) the recent reform for the ethical inclusion of vulnerable study participants to promote diversity; (2) the social value, prerequisite for everyone, especially for those who are vulnerable and the most in need; (3) the requirements for promoting the inclusion of vulnerable participants, in particular the review of the norms for placebo-controlled trials and post-trial access; (4) finally, the direction of research ethics reform to achieve social value and equitable global health.
Evaluation of the review models and approval timelines of authorities participating in the East African Medicine Regulatory Harmonisation initiative: alignment and strategies for moving forward
Authors: Ngum Nancy , Ndomondo-Sigonda Margareth , Habonimana Rémy , Siyoi Fred , Irasabwa Clarisse , Ojukwu Julia , Apolinary Felchism , Okello Andrew , Ahmada Sabrina , Walker Stuart , Salek Sam
Published: September 2024

Introduction

Medicines regulatory harmonisation has been embraced by many national regulatory authorities (NRAs) to improve public health through faster availability of safe, high-quality, and effective medical products to patients and enhanced standardisation of technical guidelines and work sharing, leading to reduced cost to pharmaceutical companies. After ten years of implementing regulatory harmonisation by the East African Community Medicines Registration Harmonization (EAC-MRH) initiative, it is now imperative for participating NRAs to rely on each other to minimise duplication of use of limited resources. Major challenges in implementing reliance are the lack of clear registration processes and delays in the approval. The aim of this study was to compare review models, target timelines and data requirements used in assessing applications by EAC-MRH NRAs so as to align and propose strategies for improvement.

Methods

A validated questionnaire that standardises and captures review processes was completed by the head of the medicine’s registration division in each of the seven EAC-MRH NRAs. A country report based on the completed questionnaire was developed for each NRA and validated by the heads of the respective authorities.

Results

Most applications received by all countries were for generics except Kenya, which received a significant number of new active substance applications (55 and 53 in 2020 and 2021). Mean approval times for generics using full review varied, with Tanzania’s time declining for the three years. Target timelines for full review for the five countries ranged between 180 calendar days (Tanzania) to the highest 330 days (Zanzibar). The three countries (Kenya, Rwanda and Uganda) utilising the verification review model had a target timeline of 90 days. All six authorities conducted abridged reviews and fast-track assessments through a priority review track. The common technical document format was mandatory for applications in all authorities. The target timeline for key milestones in the review process varied for each country with a few similarities.

Discussion

The study has provided a baseline for review models, target timelines and data requirements utilised in assessing applications for registration by EAC-MRH NRAs. Implementing the recommendations from this study will enable the NRAs to align and improve their registration processes.
Extracorporeal membrane oxygenation in acute respiratory distress syndrome caused by elderly tuberculous meningitis: a case report and review of the literature
Authors: Shi Zhaokun , Zhu Xue , Gao Wenwei , Yu Shuhui , Zhan Liying
Published: September 2024

Diagnosing and clinical management of tuberculous meningitis (TBM) are still challenging for clinicians. Analysis of cerebrospinal fluid (CSF) is an important diagnostic tool for patients with suspected central nervous system (CNS) diseases. Acute respiratory distress syndrome (ARDS), an inflammatory lung injury, can be treated by mechanical ventilation, fluid management, and even extracorporeal membrane oxygenation (ECMO). In addition, metagenomic next-generation sequencing (mNGS) can facilitate the detection of atypical, rare pathogens in clinical specimens. We report a case of a 65-year-old man with ARDS caused by TBM. He was admitted with a fever and shaking. Despite aggressive initial treatment, the patient progressed rapidly and developed ARDS. Without positive results of mNGS and culture, anti-tuberculosis (TB) treatment was started. In order to improve oxygenation levels, he was placed on veno-venous ECMO for 8 days. On day 47, the tracheotomy catheter was pulled out and sealed. The patient was conscious and could communicate with family members as normal.