bluuebunny/crossref_metadata_2025 huggingface dataset:
Hematopoietic Stem and Progenitor Cell Trained Immunity Is Heterogeneous and Cross-Protective in a Mouse Model of M. Avium Infection
Authors: Kain Bailee Nicole , Tran Brandon , Luna Pamela , Cao Ruoqiong , Le Duy , Florez Marcus Alexander , Maneix Laure , Toups Jack , Morales-Mantilla Daniel Enrique , Koh Scott , Han Hyojeong , Huang Yun Nancy , Catic Andre , Shaw Chad , King Katherine Y.
Published: December 2023

Recent studies suggest that infection epigenetically reprograms hematopoietic stem and progenitor cells (HSPCs) to enhance innate immune responses upon secondary infectious challenge, a process called “trained immunity.” Indeed, transfer of hematopoietic progenitors from mice infected with Mycobacterium bovis has been shown to confer long-lasting immunity against tuberculosis in the transplant recipients via an interferon gamma (IFNg) dependent process (Kaufmann 2018). However, much remains to be discovered about the breadth of protection conferred by trained immunity and the specific progenitor cell types responsible. We aimed to build upon our prior work examining the effects of IFNg signaling on hematopoietic stem cells to begin to answer these questions. We established a model of trained immunity in mice in response to Mycobacterium avium infection. Transfer of lineage-negative cKit+ hematopoietic progenitors from M. avium infected animals to naïve hosts was sufficient to confer protection against rechallenge in the transplant recipients up to 1 year post transplant. Macrophages derived from trained HSPCs demonstrated enhanced bacterial killing and metabolism, indicative of reprogramming in HSPCs that is conferred to innate immune cells. scRNA-seq analysis revealed that HSPCs activate IFNg-response genes heterogeneously upon primary challenge, suggesting that HSPC responses are neither monolithic nor confined to a specific cell type. Single cell transcriptomic analysis also revealed expansion of rare cell populations in the bone marrow. However, transfer of purified long-term HSCs was not sufficient to transmit trained immunity, suggesting cross-talk is required. To test whether IFNg alone is sufficient to induce trained immunity, mice were treated with a single dose of recombinant IFNg. Strikingly, this exposure was sufficient to induce enhanced bacterial killing and metabolism in bone marrow derived macrophages cultured from treated mice. To test the specificity of trained immunity, mice transplanted with influenza -trained HSPCs were challenged with M. avium infection and vice versa. Mice transplanted with influenza-trained HSPCs displayed enhanced immunity against M. avium challenge and vice versa, demonstrating cross protection against antigenically distinct pathogens. Together, these results indicate that primary infections can cause heterogeneous and long-standing HSPC responses, leading to bone marrow derived macrophages with enhanced killing capacity and cross-protectivity against alternative pathogens. These data will inform future studies to understand long term impacts of inflammatory stress on hematopoietic progenitors and the immune cells they produce.
The Bone Marrow Is the Primary Site of Thrombopoiesis
Authors: Asquith Nathan , Carminita Estelle , Rodriguez-Romera Antonio , Freire Daniela , Camacho Virginia , Becker Isabelle C. , Machlus Kellie R. , Khan Abdullah O , Italiano Joseph E.
Published: December 2023

Megakaryocytes (MKs) are large cells predominantly residing within the bone marrow, generating thousands of platelets in an elaborate proplatelet formation process. Megakaryocytes, defined by their expression of CD41, have been observed in the bone marrow and distant organs such as the spleen and lung. However, whether these megakaryocytes genuinely contribute to the mature platelet pool remains controversial. Here, we aimed to delineate which organs participate in platelet production, which mechanisms affect platelet release, and how to define alternative tissue-dependent functions of megakaryocytes. Flow cytometry data revealed significantly higher numbers of hematopoietic stem and progenitor cells and megakaryocytes in the murine bone marrow compared to spleens or perfused lungs; megakaryocyte counts were also significantly higher in cryosections of the mouse bone marrow, and also significantly increased in the bone marrow compared to spleen and lungs when analyzed by both live cell bi photon in-vivo imaging and ex vivo 3D volumetric imaging (light-sheet). Moreover, megakaryocytes cultured and differentiated from the bone marrow ex vivo had a higher capacity for proplatelet formation than MKs derived from the spleen or lung. Our analysis of previously published murine and human scRNA-seq datasets supports our observations that only a marginal fraction of megakaryocyte-like cells can be found within the lung and spleen and most likely only marginally contribute to platelet production under a steady state.
Overall Survival in Advanced Stage Mantle Cell Lymphoma after Early Autologous Stem Cell Transplantation with Cisplatin, Etoposide, Cytarabine and Melphalan (PEAM) As a Conditioning Regimen
Authors: Franco Daniel , Tellez Fernando , Solis-Armenta Ruben , Leal Alanis Araceli , Cruz Castillo Carlos , Valero Saldaña Luis Manuel , Acosta Maldonado Brenda Lizeth
Published: December 2023

Introduction.

Autologous hematopoietic stem cell transplantation (ASCT) currently is the standard of treatment for patients in first remission diagnosed with Mantle cell Lymphoma (MCL). Overall survival (OS) was reported at five-years of 57.2% in a single center retrospective study published in 2011. OS has been improved by using conventional and high intensity induction chemo immunotherapy continuing with maintenance therapy as the GELA study reports a 5 year OS of 75%. LyMa Trial has proved an improvement in the global survival and progression free survival. In this study we aimed to describe the OS patients diagnosed with MCL with PEAM as a conditioning regimen.

Methods

A retrospective study was conducted on patients diagnosed with MCL and ASCT as consolidation therapy at the Instituto Nacional de Cancerología in Mexico City between 2011 and 2022. Our institutional conditioning regimen PEAM: Cisplatin 100 mg/m2 (-4), etoposide 750 mg/m2 (-4,-3), cytarabine 800 mg/m2 (-4,-3,-2) and melphalan 140 mg/m2( 4).OS results were obtained using the Kaplan-Meier method.

Results

We analyzed 19 patients with MCL after ASCT as consolidation therapy, a median follow-up of 10 years, the median age at transplantation was 56 years (range 39- 68 y), with male predominance (68.4%). Eleven patients with at least one comorbidity, the most predominant being diabetes mellitus type II (45.5%). Most patients with ECOG score of 1 (58%), 12 patients (63%) with high risk according to Mantle Cell lymphoma International Prognostic Index (MIPI), all patients with clinical stage III-IV, 26% of them with bone marrow infiltration.

Eighteen patients (95%) received one line of chemoimmunotherapy, most were treated with R-CHOP plus + R-DHAP( 58%), 3 receive Hiper-CVAD (16%), 4 R-CHOP (21%) and only one R-DHAP . Eighteen patients (79%) with complete response, three (16%) with partial response and one patient (5%) with stable

disease before ASCT. Sixteen patients (84%) received PEAM plus rituximab as myeloablative conditioning regimen, Three (16%) PEAM without rituximab. Neutrophil recovery median was 10 days, eleven patients (58%) developed complications being febrile neutropenia the most common (82%). Fifteen patients (79%) received maintenance with rituximab. Fourteen (74%) had complete response at last follow up after ASCT, three (20%) with relapsed disease, two stable disease (10%)

Conclusion

Conventional chemoimmunotherapy is effective followed by ASCT as consolidation therapy in mantle cell lymphoma with advanced stage disease. We describe higher OS 5-years (81%) as compared with other series (57% and 75%) with similar chemo immunotherapy and conventional conditioning regimen. Three patients relapsed, all died. The OS at 5-years was 81%.
Outcomes of Multiple Myeloma Hospitalization Undergoing Autologous Stem Cell Transplantation with and without CKD: A NIS 2016 to 2020 Database Study
Authors: Neupane Niraj , Srivastava Arnav , Agrawal Shubham , Shah Anish , Budhathoki Pravash , Mahmoud Amir , Sanjeevi Aditya , Kharel Himal , Joshi Utsav , Dhakal Binod
Published: December 2023

Outcomes of Multiple Myeloma Hospitalization undergoing autologous stem cell transplantation with and without CKD: A NIS 2016 to 2020 database study.

Objective:

This study aimed to compare hospital outcomes between multiple myeloma patients undergoing autologous stem cell transplantation (ASCT) with and without chronic kidney disease (CKD) using data from the National Inpatient Sample (NIS) from 2016 to 2020.

Methods:

A retrospective analysis of the NIS database was conducted using International Classification of Diseases (ICD-10) codes to identify hospitalization who underwent ASCT for multiple myeloma. STATA version MP14.2 was used mainly for analysis. We used Fischer's exact test to compare proportions, the student's t-test to compare continuous variables, and multivariate regression analysis to calculate the adjusted odds ratio. Following are included in transplant complications (transplant rejection, failure, transplant infection).

Results:

Among 31,390 hospitalized, 4,930 had co-existing CKD. The mean age was 61.65 years. The majority were male (64.2%), with an increased Charlson comorbidity index with a majority >6. On multivariant analysis compared to hospitalization without CKD, those with CKD showed a significantly higher risk of transplant complications (adjusted odds ratio [AOR]: 1.90, 95% confidence interval [CI]: 1.21-2.99, P = 0.006), AKI (AOR: 5.43, 95% CI: 4.47-6.59, P < 0.001), AKI requiring dialysis (AOR: 2.16, 95% CI: 2.14-11.94, P < 0.001), blood transfusion (AOR: 1.32, 95% CI: 1.00-1.75, P = 0.048), and in-hospital mortality (AOR: 2.16, 95% CI: 1.13-4.12, P = 0.02). Additionally, there was a non-significant increase in the rate of platelet transfusion and ICU admission. Hence, patients with CKD had a significantly longer average length of hospital stay (18.27 vs. 16.26. p< 0.001) and higher total cost of hospital stay ($217,202 vs. $199,062, P=0.02) compared to those without CKD.

Conclusion:

Multiple myeloma patients undergoing ASCT with co-existing CKD experienced poorer hospital outcomes, including a higher risk of transplant-related complications, AKI, blood transfusion, and in-hospital mortality resulting in prolonged hospital stays and higher healthcare costs. Since multiple myeloma has a higher incidence of CKD, further studies are warranted to explore interventions based on the stage of CKD to improve the outcomes of ASCT in multiple myeloma patients with CKD.
Clinical and immunological features in ACKR1/DARC-associated neutropenia
Authors: Palmblad Jan , Sohlberg Ebba , Nilsson Christer C. , Lindqvist Henric , Deneberg Stefan , Ratcliffe Paul , Meinke Stephan , Mörtberg Anette , Klimkowska Monika , Höglund Petter
Published: December 2023

ACKR1/DARC-associated neutropenia (NP; ADAN; Online Mendelian Inheritance in Man 611862), caused by a variation in the ACKR1/DARC gene (rs2814778), is common in persons of African or Middle Eastern descent. In a cohort of 66 genetically confirmed subjects with ADAN, we show that absolute neutrophil counts (ANCs) may occasionally be lower than previously recognized (0.1 × 109-0.49 × 109/L for 9% of the subjects), which is similar to ANCs in severe congenital NP (SCNP). ANCs often normalized during inflammation, even mild. Individuals with ADAN (of 327 observed person-years) showed no cases of myelodysplastic syndrome (MDS), which is frequently encountered in SCNP. Unexpectedly, 22% presented with autoantibodies to neutrophils, compared with <1% in controls. Compared with healthy donors, subjects with ADAN demonstrated significantly lower human cationic antimicrobial protein-18/pro-leucin leucin-37 plasma levels; higher levels of nonclassical, proinflammatory, 6-sulfo LacNac-expressing monocytes; and differentially expressed plasma levels of 28 of the 239 analyzed cytokines related to immunity/inflammation, cell signaling, neutrophil activation, and angiogenesis. Collectively, more severe neutropenia in ADAN than previously assumed may complicate differential diagnoses compared with other SCNPs, and various (auto)immune/inflammatory reactions with a distinct profile may be a cause or consequence of this hereditary neutropenia.
CT-001, a novel fast-clearing factor VIIa, enhanced the hemostatic activity in postpartum samples
Authors: Sim Derek S. , Mallari Cornell R. , Hermiston Terry W. , Bae Daekyeong , Lee Sul , Allen Terrence , Gilner Jennifer , Kim Seung-Chul , James Andra H.
Published: December 2023

The hemostatic system is upregulated to protect pregnant mothers from hemorrhage during childbirth. Studies of the details just before and after delivery, however, are lacking. Recombinant factor VIIa (rFVIIa) has recently been granted approval by the European Medicines Agency for the treatment of postpartum hemorrhage (PPH). A next-generation molecule, CT-001, is being developed as a potentially safer and more efficacious rFVIIa-based therapy. We sought to evaluate the peripartum hemostatic status of pregnant women and assess the ex vivo hemostatic activity of rFVIIa and CT-001 in peripartum blood samples. Pregnant women from 2 study sites were enrolled in this prospective observational study. Baseline blood samples were collected up to 3 days before delivery. Postdelivery samples were collected 45 (±15) minutes after delivery. Between the 2 time points, soluble fibrin monomer and D-dimer increased whereas tissue factor, FVIII, FV, and fibrinogen decreased. Interestingly, the postdelivery lag time and time to peak in the thrombin generation assay were shortened, and the peak thrombin generation capacity was maintained despite the reduced levels of coagulation proteins after delivery. Furthermore, both rFVIIa and CT-001 were effective in enhancing clotting activity of postdelivery samples in activated partial thromboplastin time, prothrombin time, thrombin generation, and viscoelastic hemostatic assays, with CT-001 demonstrating greater activity. In conclusion, despite apparent ongoing consumption of coagulation factors at the time of delivery, thrombin output was maintained. Both rFVIIa and CT-001 enhanced the upregulated hemostatic activity in postdelivery samples, and consistent with previous studies comparing CT-001 and rFVIIa in vitro and in in vivo, CT-001 demonstrated greater activity than rFVIIa.
Effect of Emi1 gene silencing on the proliferation and invasion of human breast cancer cells
Authors: Kuang Ying , Huang Shengwen , Tang Shifan , Zhuo Zhaozhen , Linghu Keyan
Published: December 2023

Breast cancer is the most common malignant tumour in women. The early silk-splitting inhibitor protein 1 Emi1 is responsible for mediating ubiquitin protein degradation. The present study investigated the effects of the decreased expression of the Emil gene on the proliferation and invasion of breast cancer cells. The interference efficiency of small interfering ribonucleic acid (siRNA) was quantitatively verified using fluorescence real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting, and the effect of Emi1 gene silencing on cell vitality and invasion was determined using MTT and Transwell assays, respectively. The expression of the proliferation genes programmed cell death receptor 4 (PDCD-4), fatty acid synthase ligand (FasL), PTEN and RhoB, along with the invasive genes Maspin, TIMP3 and RECK, was measured using fluorescence RT-qPCR. In breast cancer cells, siRNA successfully reduced the expression of the Emi1 gene, and the expression level of the cell proliferation genes PDCD-4, FasL, PTEN and RhoB, along with invasive genes Maspin, TIMP3 and RECK, decreased significantly (P < 0.05). Furthermore, Emi1 gene silencing reduced the proliferation and invasion abilities of MDA-MB-231 and SUM149PT cells by reducing the expression of proliferative and invasive genes.
Range of chromatin accessibility configurations are permissive of GABAergic fate acquisition in developing mouse brain
Authors: Kilpinen Sami , Heliölä Heidi , Achim Kaia
Published: December 2023

In recent single-cell -omics studies, both the differential activity of transcription factors regulating cell fate determination and differential genome activation have been tested for utility as descriptors of cell types. Naturally, genome accessibility and gene expression are interlinked. To understand the variability in genomic feature activation in the GABAergic neurons of different spatial origins, we have mapped accessible chromatin regions and mRNA expression in single cells derived from the developing mouse central nervous system (CNS). We first defined a reference set of open chromatin regions for scATAC-seq read quantitation across samples, allowing comparison of chromatin accessibility between brain regions and cell types directly. Second, we integrated the scATAC-seq and scRNA-seq data to form a unified resource of transcriptome and chromatin accessibility landscape for the cell types in di- and telencephalon, midbrain and anterior hindbrain of E14.5 mouse embryo. Importantly, we implemented resolution optimization at the clustering, and automatized the cell typing step. We show high level of concordance between the cell clustering based on the chromatin accessibility and the transcriptome in analyzed neuronal lineages, indicating that both genome and transcriptome features can be used for cell type definition. Hierarchical clustering by the similarity in accessible chromatin reveals that the genomic feature activation correlates with neurotransmitter phenotype, selector gene expression, cell differentiation stage and neuromere origins.
Dynamic physiological and transcriptomic changes reveal memory effects of salt stress in maize
Authors: Zhu Zhiying , Dai Yan , Yu Guangrun , Zhang Xin , Chen Qi , Kou Xiaobing , Mehareb Eid M. , Raza Ghulam , Zhang Baohong , Wang Baohua , Wang Kai , Han Jinlei
Published: December 2023

Background

Pre-exposing plants to abiotic stresses can induce stress memory, which is crucial for adapting to subsequent stress exposure. Although numerous genes involved in salt stress response have been identified, the understanding of memory responses to salt stress remains limited.

Results

In this study, we conducted physiological and transcriptional assays on maize plants subjected to recurrent salt stress to characterize salt stress memory. During the second exposure to salt stress, the plants exhibited enhanced salt resistance, as evidenced by increased proline content and higher POD and SOD activity, along with decreased MDA content, indicative of physiological memory behavior. Transcriptional analysis revealed fewer differentially expressed genes and variations in response processes during the second exposure compared to the first, indicative of transcriptional memory behavior. A total of 2,213 salt stress memory genes (SMGs) were identified and categorized into four response patterns. The most prominent group of SMGs consisted of genes with elevated expression during the first exposure to salt stress but reduced expression after recurrent exposure to salt stress, or vice versa ([+ / −] or [− / +]), indicating that a revised response is a crucial process in plant stress memory. Furthermore, nine transcription factors (TFs) (WRKY40, WRKY46, WRKY53, WRKY18, WRKY33, WRKY70, MYB15, KNAT7, and WRKY54) were identified as crucial factors related to salt stress memory. These TFs regulate over 53% of SMGs, underscoring their potential significance in salt stress memory.

Conclusions

Our study demonstrates that maize can develop salt stress memory, and the genes identified here will aid in the genetic improvement of maize and other crops.
Cultivar-specific dynamics: unravelling rhizosphere microbiome responses to water deficit stress in potato cultivars
Authors: Martins Benoit Renaud , Siani Roberto , Treder Krzysztof , Michałowska Dorota , Radl Viviane , Pritsch Karin , Schloter Michael
Published: December 2023

Background

Growing evidence suggests that soil microbes can improve plant fitness under drought. However, in potato, the world’s most important non-cereal crop, the role of the rhizosphere microbiome under drought has been poorly studied. Using a cultivation independent metabarcoding approach, we examined the rhizosphere microbiome of two potato cultivars with different drought tolerance as a function of water regime (continuous versus reduced watering) and manipulation of soil microbial diversity (i.e., natural (NSM), vs. disturbed (DSM) soil microbiome).

Results

Water regime and soil pre-treatment showed a significant interaction with bacterial community composition of the sensitive (HERBST) but not the resistant cultivar (MONI). Overall, MONI had a moderate response to the treatments and its rhizosphere selected Rhizobiales under reduced watering in NSM soil, whereas Bradyrhizobium, Ammoniphilus, Symbiobacterium and unclassified Hydrogenedensaceae in DSM soil. In contrast, HERBST response to the treatments was more pronounced. Notably, in NSM soil treated with reduced watering, the root endophytic fungus Falciphora and many Actinobacteriota members (Streptomyces, Glycomyces, Marmoricola, Aeromicrobium, Mycobacterium and others) were largely represented. However, DSM soil treatment resulted in no fungal taxa and fewer enrichment of these Actinobacteriota under reduced watering. Moreover, the number of bacterial core amplicon sequence variants (core ASVs) was more consistent in MONI regardless of soil pre-treatment and water regimes as opposed to HERBST, in which a marked reduction of core ASVs was observed in DSM soil.

Conclusions

Besides the influence of soil conditions, our results indicate a strong cultivar-dependent relationship between the rhizosphere microbiome of potato cultivars and their capacity to respond to perturbations such as reduced soil moisture. Our study highlights the importance of integrating soil conditions and plant genetic variability as key factors in future breeding programs aiming to develop drought resistance in a major food crop like potato. Elucidating the molecular mechanisms how plants recruit microbes from soil which help to mitigate plant stress and to identify key microbial taxa, which harbour the respective traits might therefore be an important topic for future research.
Arabidopsis seedlings respond differentially to nutrient efficacy of three rock meals by regulating root architecture and endogenous auxin homeostasis
Authors: Zhang Tianjiao , Zhang Sainan , Yang Shaohui , Zhang Jianchao , Wang Jiehua , Teng H. Henry
Published: December 2023

Background

Plants show developmental plasticity with variations in environmental nutrients. Considering low-cost rock dust has been identified as a potential alternative to artificial fertilizers for more sustainable agriculture, the growth responses of Arabidopsis seedlings on three rock meals (basalt, granite, and marlstone) were examined for the different foraging behavior, biomass accumulation, and root architecture.

Results

Compared to ½ MS medium, basalt and granite meal increased primary root length by 13% and 38%, respectively, but marlstone caused a 66% decrease, and they all drastically reduced initiation and elongation of lateral roots but lengthened root hairs. Simultaneous supply of organic nutrients and trace elements increased fresh weight due to the increased length of primary roots and root hairs. When nitrogen (N), phosphorus (P), and potassium (K) were supplied individually, N proved most effective in improving fresh weight of seedlings growing on basalt and granite, whereas K, followed by P, was most effective for those growing on marlstone. Unexpectedly, the addition of N to marlstone negatively affected seedling growth, which was associated with repressed auxin biosynthesis in roots.

Conclusions

Our data indicate that plants can recognize and adapt to complex mineral deficiency by adjusting hormonal homeostasis to achieve environmental sensitivity and developmental plasticity, which provide a basis for ecologically sound and sustainable strategies to maximize the use of natural resources and reduce the production of artificial fertilizers.
Identification of novel sources of partial and incomplete hypersensitive resistance to rust and associated genomic regions in common bean
Authors: Leitão Susana Trindade , Rubiales Diego , Vaz Patto Maria Carlota
Published: December 2023

Common bean (Phaseolus vulgaris) is one of the legume crops most consumed worldwide and bean rust is one of the most severe foliar biotrophic fungal diseases impacting its production. In this work, we searched for new sources of rust resistance (Uromyces appendiculatus) in a representative collection of the Portuguese germplasm, known to have accessions with an admixed genetic background between Mesoamerican and Andean gene pools. We identified six accessions with incomplete hypersensitive resistance and 20 partially resistant accessions of Andean, Mesoamerican, and admixed origin. We detected 11 disease severity-associated single-nucleotide polymorphisms (SNPs) using a genome-wide association approach. Six of the associations were related to partial (incomplete non-hypersensitive) resistance and five to incomplete hypersensitive resistance, and the proportion of variance explained by each association varied from 4.7 to 25.2%. Bean rust severity values ranged from 0.2 to 49.1% and all the infection types were identified, reflecting the diversity of resistance mechanisms deployed by the Portuguese germplasm.

The associations with U. appendiculatus partial resistance were located in chromosome Pv08, and with incomplete hypersensitive resistance in chromosomes Pv06, Pv07, and Pv08, suggesting an oligogenic inheritance of both types of resistance. A resolution to the gene level was achieved for eight of the associations. The candidate genes proposed included several resistance-associated enzymes, namely β-amylase 7, acyl-CoA thioesterase, protein kinase, and aspartyl protease. Both SNPs and candidate genes here identified constitute promising genomics targets to develop functional molecular tools to support bean rust resistance precision breeding.
The impact of social support, physical and psychological performance on sleep outcomes in Iranian older adults: a case-control study
Authors: Salehi Zahra , Pasha Hajar , Hosseini Seyed Reza , Kheirkhah Farzan , Bijani Ali
Published: December 2023

Background

Sleep quality is one of the most important factors to improve the quality of life in older adults and physical and mental health plays an essential role in better sleep quality. This study aimed to determine the impact of social support, and physical and psychological performance on sleep outcomes in Iranian older adults.

Methods

In this case-control study, 400 elder people, who were exposed to sleep problems, and 400 people without sleep problems were randomly selected during 2016–2017 in Amirkola, Iran. Subjects in the case and control groups were matched in terms of gender and age. The demographic characteristics, Duke Social Support Questionnaire (DSSI), Physical Activity Scale for the Elderly (PASE), Activity of Daily Living (ADL), Instrumental Activity of Daily Living (IADL), Mini-Mental State Examination (MMSE), and Pittsburgh Sleep Quality Questionnaire (PSQI) questionnaires were used to collect data. T-test, Chi-square, Pearson Correlation coefficient, and multiple Logistic regression were used for data analysis.

Results

The mean score of DSSI and its domains including social interaction (DSSI.Int) and social satisfaction (DSSI.Sat) were 28.15 ± 3.55, 9.31 ± 1.23, and 18.84 ± 2.88 in the case group and 28.87 ± 3.20, 9.48 ± 1.10, and 19.83 ± 2.44 in the control group, respectively. In this study, the mean scores of MMSE, PASE, ADL, and IADL were 25.36 ± 3.95, 101.71 ± 56.99, 13/97 ± 0.37, 20.59 ± 2/79; respectively. There was a significant inverse correlation between poor sleep quality with DSSI score (rho = -0.165, P < 0.0001), DSSI.Int (rho = -0.113, P < 0.001), DSSI.Sat (rho = -0.160, P < 0.0001), PASE (rho=-0.160, P < 0.0001), and IADL (rho = -0.112, P < 0.001) score. Therefore, more social support and physical activity improved the quality of sleep. There was a significant negative relationship between DSSI, and its domains with sleep quality in terms of gender. DSSI (rho = 0.25, P < 0.0001), DSSI.Int (P < 0.0001, rho=-0.18), and DSSI.Sat (P < 0.0001, rho=-0.22) was significant in men but not in women. The results of the adjusted logistic regression revealed a significant association between sleep quality problems and DSSI (p < 0.045, OR = 1.40), the use of hypnotic drugs (p < 0.0001, OR = 7.56), and occupation (p <0.03, OR= 12.66).

Conclusions

The results of the present study suggest that low social support and all its domains, PASE, IADL, and using hypnotic drugs may play a role in the development of sleep problems. It can be used as an effective, safe, and low-cost strategy for promoting sleep quality in older adults.
HIV assisted partner services (aPS) to support integrated HIV and hypertension screening in Kenya: a pre-post intervention study
Authors: Wamuti Beatrice , Sambai Betsy , Magambo Christine , Ndegwa Margaret , Macharia Paul , M.Temu Tecla , Farquhar Carey , Bukusi David
Published: December 2023

Background

People living with HIV (PLWH) have a higher risk of developing hypertension compared to HIV uninfected individuals. HIV assisted partner services (aPS), where PLWH are assisted by a healthcare provider to disclose their status to sexual and / or drug injecting partner(s), offers an opportunity for integrated HIV and hypertension screening. We evaluated the feasibility of the aPS model in supporting integrated HIV and hypertension screening at the Kenyatta National Hospital, Kenya.

Methods

Between August 2019 and December 2020, we conducted a pre-post intervention study. We enrolled women receiving HIV testing services (HTS) with confirmed hypertension (female index clients) and traced their male relatives for HIV and hypertension screening and reviewed management at 3-months. Hypertension was defined as systolic blood pressure (SBP) ≥ 140 mmHg, diastolic blood pressure (DBP) ≥ 90 mmHg, and/or use of antihypertensive medication.

Results

One hundred female index clients (median age: 55 years; interquartile range (IQR): 47–65) mentioned 165 male relatives (median: 49 years; IQR: 40–59) of whom 35% (n = 58/165) were enrolled. Of the male relatives, 29% had hypertension (n = 17/58), 34% had pre-hypertension (n = 20/58), and none were HIV-positive (n = 0/58). Among the female index clients, there was a statistically significant decline in SBP (pre: 156 mmHg, post: 133 mmHg, p-value: < 0.0001) and DBP (pre: 97 mmHg, post: 80 mmHg, p-value: < 0.0001), and increase in antihypertensive medication uptake (pre: 91%, n = 84/92; post: 98%, n = 90/92; X2: 4.3931, p-value: 0.036) relative to baseline. Among the male relatives, there was a statistically significant increase in antihypertensive medication uptake among those with hypertension (pre: 13%, n = 6/46; post: 17%, n = 8/46; X2: 32.7750, p-value: < 0.0001) relative to baseline.

Conclusion

HIV aPS holds promise for integrated HIV and hypertension screening among at-risk clients and their families. Twenty-nine percent of the male relatives had hypertension, higher than the national prevalence (24%), while one-third had pre-hypertension. We observed relatively high participant retention, reductions in blood pressure, and increase in antihypertensive medication uptake among those with confirmed hypertension. Future research expanding the aPS model to other non-communicable diseases through larger studies with longer follow-ups is required to better assess causal relationships and optimize integrated service delivery.
Understanding gender differences of people with HIV newly diagnosed or returning to care with advanced HIV disease in Malawi: a qualitative study
Authors: Katirayi Leila , Maphosa Thulani , Chilikutali Lloyd , Chamanga Rachel K , Petersson Josephine , Khatib Sarah , Munthali Boswell , Nyirenda Rose , Matiya Eddie , Nyirenda Laywell , Tiam Appolinaire , Denoeud-Ndam Lise
Published: December 2023

Background

Despite tremendous progress in improving antiretroviral therapy (ART) access, advanced HIV disease (AHD) still remains a challenge globally. Reasons for delayed presentation to care and ART adherence may be affected by gender. We present qualitative study findings on gender differences in decisions for HIV testing and ART initiation/adherence in adults with AHD in Malawi.

Methods

We used a qualitative study design, interviewing 16 men and 16 women aged 18 years and above diagnosed with AHD in sites implementing an optimized package of AHD care, from December 2021-February 2022. We included study participants receiving AHD services for at least two months. We also interviewed 16 lay workers and 16 health care workers supporting people living with AHD. In-depths interviews (IDIs) were conducted in English or Chichewa by trained research assistants using semi-structured interview guides. A short-answer analysis was conducted, and findings were interpreted according to thematic areas.

Results

Both men and women reported stigma as a main barrier influencing their decision to test for HIV and to initiate and adhere to ART. Fear of side effects, insufficient food, and the need for more information were other barriers reported among men and women as well as perceived as barriers by HCWs. Men appear to have tested later for HIV and stated that they were waiting until experiencing significant symptoms before testing. According to clients and HCWs, men were also less inclined to initiate ART after a HIV diagnosis, whereas women were motivated to start treatment to remain healthy and care for the family. Both genders reported that treatment could be delayed if they were feeling healthy. Treatment fatigue was reported among all groups as the main reason to discontinue treatment.

Conclusions

There were similarities and differences between genders in decision-making about HIV care. Concerns about stigma were important reasons for delay in HIV care in both genders. Motivations for accessing HIV treatment and care were different among men and women, pushing the need for gender-tailored counseling services and community messaging that educate both men and women on the benefits of initiating ART early, in turn reducing the number of people presenting with AHD.

Trial registration

NCT05510973, first registration 22/08/2022.
Utility of needle biopsy in centrally located lung cancer for genome analysis: a retrospective cohort study
Authors: Kunimasa Kei , Matsumoto Shingo , Honma Keiichiro , Tamiya Motohiro , Inoue Takako , Kawamura Takahisa , Tanada Satoshi , Miyazaki Akito , Kanzaki Ryu , Maniwa Tomohiro , Okami Jiro , Matsumoto Yuji , Goto Koichi , Nishino Kazumi
Published: December 2023

Background

It is essential to collect a sufficient amount of tumor tissue for successful next-generation sequencing (NGS) analysis. In this study, we investigated the clinical risk factors for avoiding re-biopsy for NGS analysis (re-genome biopsy) in cases where a sufficient amount of tumor tissue could not be collected by bronchoscopy.

Methods

We investigated the association between clinical factors and the risk of re-genome biopsy in patients who underwent transbronchial biopsy (TBB) or endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and required re-genome biopsy in cases enrolled in LC-SCRUM Asia, a prospective nationwide genome screening project in Japan. We also examined whether the frequency of re-genome biopsy decreased between the first and second halves of the enrolment period.

Results

Of the 572 eligible patients, 236 underwent TBB, and 134 underwent EBUS-TBNA. Twenty-four TBBs required re-genome biopsy, and multivariate analysis showed that the risk of re-genome biopsy was significantly increased in lesions where the tumor lesion was centrally located. In these cases, EBUS-TBNA should be utilized even if the lesion is a pulmonary lesion. However, it should be noted that even with EBUS-TBNA, lung field lesions are at a higher risk of re-canalization than mediastinal lymph node lesions. It was also found that even when tumor cells were detected in rapid on-site evaluation, a sufficient amount of tumor tissue was not always collected.

Conclusions

For centrally located pulmonary mass lesions, EBUS-TBNA, rather than TBB, can be used to obtain tumor tissues that can be analyzed by NGS.
Modeling longitudinal oral health status and pneumonia risk: secondary data analyses of an integrated dental-medical cohort
Authors: Berg Richard L. , Glurich Ingrid , Panny Aloksagar , Scannapieco Frank A. , Miecznikowski Jeffrey , VanWormer Jeffrey , Acharya Amit
Published: December 2023

Background

Mounting evidence indicates potential associations between poor oral health status (OHS) and increased pneumonia risk. Relative pneumonia risk was assessed in the context of longitudinally documented OHS.

Methods

Electronic medical/dental patient data captured from 2007 through 2019 were retrieved from the integrated health records of Marshfield Clinic Health Systems. Participant eligibility initiated with an assessment of OHS, stratified into the best, moderate, or worst OHS groups, with the additional criterion of ‘no pneumonia diagnosis in the past 90 days’. Pneumonia incidence was longitudinally monitored for up to 1 year from each qualifying dental visit. Models were assessed, with and without adjustment for prior pneumonia incidence, adjusted for smoking and subjected to confounding mitigation attributable to known pneumonia risk factors by applying propensity score analysis. Time-to-event analysis and proportional hazard modeling were applied to investigate relative pneumonia risk over time among the OHS groups.

Results

Modeling identified associations between any incident pneumonia subtype and ‘number of missing teeth’ (p < 0.001) and ‘clinically assessed periodontal status’ (p < 0.01), which remained significant following adjustment for prior pneumonia incidence and smoking. The hazard ratio (HR) for ‘any incident pneumonia’ in the best OHS group for ‘number of missing teeth’ was 0.65, 95% confidence interval (CI) [0.54 − 0.79] (unadjusted) and 0.744, 95% CI [0.61 − 0.91] (adjusted). The HR for ‘any incident pneumonia’ in the best ‘clinically assessed periodontal status’ group was 0.72, 95% CI [0.58 − 0.90] (unadjusted) and 0.78, 95% CI [0.62 − 0.97] (adjusted).

Conclusion/clinical relevance

Poor OHS increased pneumonia risk. Proactive attention of medical providers to patient OHS and health literacy surrounding oral-systemic disease association is vital, especially in high-risk populations.
Nursing students’ learning flow, self-efficacy and satisfaction in virtual clinical simulation and clinical case seminar
Authors: Choi Hyein , Tak Sunghee H. , Lee Dayeon
Published: December 2023

Background

Virtual clinical simulations and clinical case seminar become widely utilized to address these constraints and help nursing students acquire clinical competencies as the limitations on practicum opportunities have been intensified by the COVID-19 pandemic. The purpose of this study was to examine learning flow, self-efficacy and satisfaction in virtual clinical simulation and clinical case seminar among nursing students.

Methods

A descriptive cross-sectional study was used. Forty-two junior nursing students completed survey questionnaires after participating in computer-based virtual clinical simulation and clinical case seminar, which aimed at acquiring knowledge and care skills in geriatric nursing.

Results

Significant differences in two methods were found in learning flow which included challenge-skill balance (t = -2.24, p < .05) and action-awareness merge (t = -3.32, p < .01). There was no significant difference in learning self-efficacy (t=-1.52, p = .137) and learning satisfaction (t=-0.92, p = .365).

Conclusions

When there’s a mismatch between the perceived challenge and the students’ skill levels, it can hinder the learning process. Therefore, instructors should evaluate the clinical skill levels of their students and make necessary adjustments to the difficulty levels of simulation and clinical case seminar accordingly.
A patient’s perspective on care decisions: a qualitative interview study
Authors: Briedé S. , Brandwijk O. N. , van Charldorp T. C. , Kaasjager H. A. H.
Published: December 2023

Background and Objectives

Discussing treatment wishes and limitations during medical consultations aims to enable patients to define goals and preferences for future care. Patients and physicians, however, face multiple barriers, resulting in postponing or avoiding the conversation. The aim of this study was to explore an internal medicine outpatient clinic population’s perception on (discussing) treatment wishes and limitations.

Methods

Semi-structured interviews were conducted in two rounds with 44 internal medicine outpatient clinic patients at the University Medical Centre Utrecht, a tertiary care teaching medical centre in the Netherlands. Interviews were transcribed verbatim and thematically analysed with a phenomenological approach and inductive, data-driven coding.

Results

Four themes were identified, two (1–2) represent a deep conviction, two (3–4) are practically oriented: (1) patients associate treatment wishes and limitations with the end-of-life, making it sensitive and currently irrelevant, (2) patients assume this process leads to fixed choices, whilst their wishes might be situation dependent, (3) treatment wishes and limitations are about balancing whether a treatment ‘is worth it’, in which several subthemes carry weight, (4) the physician is assigned a key role.

Conclusion and practice implications

The themes provide starting points for future interventions. It should be emphasized that care decisions are a continuous, dynamic process, relevant at any time in any circumstance and the physician should be aware of his/her key role.
Predicting drug response from single-cell expression profiles of tumours
Authors: Pellecchia Simona , Viscido Gaetano , Franchini Melania , Gambardella Gennaro
Published: December 2023

Background

Intra-tumour heterogeneity (ITH) presents a significant obstacle in formulating effective treatment strategies in clinical practice. Single-cell RNA sequencing (scRNA-seq) has evolved as a powerful instrument for probing ITH at the transcriptional level, offering an unparalleled opportunity for therapeutic intervention.

Results

Drug response prediction at the single-cell level is an emerging field of research that aims to improve the efficacy and precision of cancer treatments. Here, we introduce DREEP (Drug Response Estimation from single-cell Expression Profiles), a computational method that leverages publicly available pharmacogenomic screens from GDSC2, CTRP2, and PRISM and functional enrichment analysis to predict single-cell drug sensitivity from transcriptomic data. We validated DREEP extensively in vitro using several independent single-cell datasets with over 200 cancer cell lines and showed its accuracy and robustness. Additionally, we also applied DREEP to molecularly barcoded breast cancer cells and identified drugs that can selectively target specific cell populations.

Conclusions

DREEP provides an in silico framework to prioritize drugs from single-cell transcriptional profiles of tumours and thus helps in designing personalized treatment strategies and accelerating drug repurposing studies. DREEP is available at https://github.com/gambalab/DREEP.
Coronary microvascular function in male physicians with burnout and job stress: an observational study
Authors: von Känel Roland , Princip Mary , Holzgang Sarah A. , Garefa Chrysoula , Rossi Alexia , Benz Dominik C. , Giannopoulos Andreas A. , Kaufmann Philipp A. , Buechel Ronny R. , Zuccarella-Hackl Claudia , Pazhenkottil Aju P.
Published: December 2023

Background

As a professional group, physicians are at increased risk of burnout and job stress, both of which are associated with an increased risk of coronary heart disease that is at least as high as that of other professionals. This study aimed to examine the association of burnout and job stress with coronary microvascular function, a predictor of major adverse cardiovascular events.

Methods

Thirty male physicians with clinical burnout and 30 controls without burnout were included. Burnout was assessed with the Maslach Burnout Inventory and job stress with the effort-reward imbalance and overcommitment questionnaire. All participants underwent myocardial perfusion positron emission tomography to quantify endothelium-dependent (cold pressor test) and endothelium-independent (adenosine challenge) coronary microvascular function. Burnout and job stress were regressed on coronary flow reserve (primary outcome) and two additional measures of coronary microvascular function in the same model while adjusting for age and body mass index.

Results

Burnout and job stress were significantly and independently associated with endothelium-dependent microvascular function. Burnout was positively associated with coronary flow reserve, myocardial blood flow response, and hyperemic myocardial blood flow (r partial = 0.28 to 0.35; p-value = 0.008 to 0.035). Effort-reward ratio (r partial =  − 0.32 to − 0.38; p-value = 0.004 to 0.015) and overcommitment (r partial =  − 0.30 to − 0.37; p-value = 0.005 to 0.022) showed inverse associations with these measures.

Conclusions

In male physicians, burnout and high job stress showed opposite associations with coronary microvascular endothelial function. Longitudinal studies are needed to show potential clinical implications and temporal relationships between work-related variables and coronary microvascular function. Future studies should include burnout and job stress for a more nuanced understanding of their potential role in cardiovascular health.
Identification of differentially expressed genes associated with the pathogenesis of gastric cancer by bioinformatics analysis
Authors: Abdolahi Fatemeh , Shahraki Ali , Sheervalilou Roghayeh , Mortazavi Sedigheh Sadat
Published: December 2023

Aim

Gastric cancer (GC) is one of the most diagnosed cancers worldwide. GC is a heterogeneous disease whose pathogenesis has not been entirely understood. Besides, the GC prognosis for patients remains poor. Hence, finding reliable biomarkers and therapeutic targets for GC patients is urgently needed.

Methods

GSE54129 and GSE26942 datasets were downloaded from Gene Expression Omnibus (GEO) database to detect differentially expressed genes (DEGs). Then, gene set enrichment analyses and protein-protein interactions were investigated. Afterward, ten hub genes were identified from the constructed network of DEGs. Then, the expression of hub genes in GC was validated. Performing survival analysis, the prognostic value of each hub gene in GC samples was investigated. Finally, the databases were used to predict microRNAs that could regulate the hub genes. Eventually, top miRNAs with more interactions with the list of hub genes were introduced.

Results

In total, 203 overlapping DEGs were identified between both datasets. The main enriched KEGG pathway was “Protein digestion and absorption.” The most significant identified GO terms included “primary alcohol metabolic process,” “basal part of cell,” and “extracellular matrix structural constituent conferring tensile strength.” Identified hub modules were COL1A1, COL1A2, TIMP1, SPP1, COL5A2, THBS2, COL4A1, MUC6, CXCL8, and BGN. The overexpression of seven hub genes was associated with overall survival. Moreover, among the list of selected miRNAs, hsa-miR-27a-3, hsa-miR-941, hsa-miR-129-2-3p, and hsa-miR-1-3p, were introduced as top miRNAs targeting more than five hub genes.

Conclusions

The present study identified ten genes associated with GC, which may help discover novel prognostic and diagnostic biomarkers as well as therapeutic targets for GC. Our results may advance the understanding of GC occurrence and progression.