bluuebunny/crossref_metadata_2025 huggingface dataset:
CD155/PVR determines acute myeloid leukemia targeting by Delta One T cells
Authors: Mensurado Sofia , Condeço Carolina , Sánchez-Martínez Diego , Shirley Sara , Coelho Rui M. L. , Tirado Néstor , Vinyoles Meritxell , Blanco-Domínguez Rafael , Barros Leandro , Galvão Beatriz , Custódio Noélia , Gomes da Silva Maria , Menéndez Pablo , Silva-Santos Bruno
Published: March 2024

Relapsed or refractory acute myeloid leukemia (AML) remains a major therapeutic challenge. We have recently developed a Vδ1+ γδ T cell–based product for adoptive immunotherapy, named Delta One T (DOT) cells, and demonstrated their cytolytic capacity to eliminate AML cell lines and primary blasts in vitro and in vivo. However, the molecular mechanisms responsible for the broad DOT-cell recognition of AML cells remain poorly understood. Here, we dissected the role of natural killer (NK) cell receptor ligands in AML cell recognition by DOT cells. Screening of multiple AML cell lines highlighted a strong upregulation of the DNAM-1 ligands, CD155/pulmonary vascular resistance (PVR), CD112/nectin-2, as well as the NKp30 ligand, B7-H6, in contrast with NKG2D ligands. CRISPR-mediated ablation revealed key nonredundant and synergistic contributions of PVR and B7-H6 but not nectin-2 to DOT-cell targeting of AML cells. We further demonstrate that PVR and B7-H6 are critical for the formation of robust immunological synapses between AML and DOT cells. Importantly, PVR but not B7-H6 expression in primary AML samples predicted their elimination by DOT cells. These data provide new mechanistic insight into tumor targeting by DOT cells and suggest that assessing PVR expression levels may be highly relevant to DOT cell–based clinical trials.
CD19-CD28: an affinity-optimized CD28 agonist for combination with glofitamab (CD20-TCB) as off-the-shelf immunotherapy
Authors: Sam Johannes , Hofer Thomas , Kuettel Christine , Claus Christina , Thom Jenny , Herter Sylvia , Georges Guy , Korfi Koorosh , Lechmann Martin , Eigenmann Miro Julian , Marbach Daniel , Jamois Candice , Lechner Katharina , Krishnan Sreenath M. , Gaillard Brenda , Marinho Joana , Kronenberg Sven , Kunz Leo , Wilson Sabine , Briner Stefanie , Gebhardt Samuel , Varol Ahmet , Appelt Birte , Nicolini Valeria , Speziale Dario , Bez Miriam , Bommer Esther , Eckmann Jan , Hage Carina , Limani Florian , Jenni Silvia , Schoenle Anne , Le Clech Marine , Vallier Jean-Baptiste Pierre , Colombetti Sara , Bacac Marina , Gasser Stephan , Klein Christian , Umaña Pablo
Published: March 2024

Effective T-cell responses not only require the engagement of T-cell receptors (TCRs; “signal 1”), but also the availability of costimulatory signals (“signal 2”). T-cell bispecific antibodies (TCBs) deliver a robust signal 1 by engaging the TCR signaling component CD3ε, while simultaneously binding to tumor antigens. The CD20-TCB glofitamab redirects T cells to CD20-expressing malignant B cells. Although glofitamab exhibits strong single-agent efficacy, adding costimulatory signaling may enhance the depth and durability of T-cell–mediated tumor cell killing. We developed a bispecific CD19-targeted CD28 agonist (CD19-CD28), RG6333, to enhance the efficacy of glofitamab and similar TCBs by delivering signal 2 to tumor-infiltrating T cells. CD19-CD28 distinguishes itself from the superagonistic antibody TGN1412, because its activity requires the simultaneous presence of a TCR signal and CD19 target binding. This is achieved through its engineered format incorporating a mutated Fc region with abolished FcγR and C1q binding, CD28 monovalency, and a moderate CD28 binding affinity. In combination with glofitamab, CD19-CD28 strongly increased T-cell effector functions in ex vivo assays using peripheral blood mononuclear cells and spleen samples derived from patients with lymphoma and enhanced glofitamab-mediated regression of aggressive lymphomas in humanized mice. Notably, the triple combination of glofitamab with CD19-CD28 with the costimulatory 4-1BB agonist, CD19–4-1BBL, offered substantially improved long-term tumor control over glofitamab monotherapy and respective duplet combinations. Our findings highlight CD19-CD28 as a safe and highly efficacious off-the-shelf combination partner for glofitamab, similar TCBs, and other costimulatory agonists. CD19-CD28 is currently in a phase 1 clinical trial in combination with glofitamab. This trial was registered at www.clinicaltrials.gov as #NCT05219513.
An across breed, diet and tissue analysis reveals the transcription factor NR1H3 as a key mediator of residual feed intake in beef cattle
Authors: Keogh Kate , Kenny D. A. , Alexandre P. A. , McGee M. , Reverter A.
Published: March 2024

Background

Provision of feed is a major determinant of overall profitability in beef production systems, accounting for up to 75% of the variable costs. Thus, improving cattle feed efficiency, by way of determining the underlying genomic control and subsequently selecting for feed efficient cattle, provides a method through which feed input costs may be reduced. The objective of this study was to undertake gene co-expression network analysis using RNA-Sequence data generated fromLongissimus dorsiand liver tissue samples collected from steers of two contrasting breeds (Charolais and Holstein-Friesian) divergent for residual feed intake (RFI), across two consecutive distinct dietary phases (zero-grazed grass and high-concentrate). Categories including differentially expressed genes (DEGs) based on the contrasts of RFI phenotype, breed and dietary source, as well as key transcription factors and proteins secreted in plasma were utilised as nodes of the gene co-expression network.

Results

Of the 2,929 DEGs within the network analysis, 1,604 were reported to have statistically significant correlations (≥ 0.80), resulting in a total of 43,876 significant connections between genes. Pathway analysis of clusters of co-expressed genes revealed enrichment of processes related to lipid metabolism (fatty acid biosynthesis, fatty acid β-oxidation, cholesterol biosynthesis), immune function, (complement cascade, coagulation system, acute phase response signalling), and energy production (oxidative phosphorylation, mitochondrial L-carnitine shuttle pathway) based on genes related to RFI, breed and dietary source contrasts.

Conclusions

Although similar biological processes were evident across the three factors examined, no one gene node was evident across RFI, breed and diet contrasts in both liver and muscle tissues. However within the liver tissue, theIRX4,NR1H3,HOXA13andZNF648gene nodes, which all encode transcription factors displayed significant connections across the RFI, diet and breed comparisons, indicating a role for these transcription factors towards the RFI phenotype irrespective of diet and breed. Moreover, theNR1H3gene encodes a protein secreted into plasma from the hepatocytes of the liver, highlighting the potential for this gene to be explored as a robust biomarker for the RFI trait in beef cattle.
RNA-seq analysis reveals narrow differential gene expression in MEP and MVA pathways responsible for phytochemical divergence in extreme genotypes of Thymus daenensis Celak
Authors: Ahmadi Hosein , Fatahi Reza , Zamani Zabihollah , Shokrpour Majid , Sheikh-Assadi Morteza , Poczai Peter
Published: March 2024

Background

Here, we investigated the underlying transcriptional-level evidence behind phytochemical differences between two metabolically extreme genotypes of Thymus daenensis. The genotypes ‘Zagheh-11’ (thymol/carvacrol type, poor in essential oil [EO] [2.9%] but rich in triterpenic acids) and ‘Malayer-21’ (thymol type and rich in EO [3.8%]) were selected from an ongoing breeding program and then clonally propagated for further experimental use.

Materials and methods

GC-MS, GC-FID, and HPLC-PDA were utilized to monitor the fluctuation of secondary metabolites at four phenological stages (vegetative, bud burst, early, and full-flowering stages). The highest phytochemical divergence was observed at early flowering stage. Both genotypes were subjected to mRNA sequencing (approximately 100 million paired reads) at the aforementioned stage. The expression patterns of four key genes involved in the biosynthesis of terpenoids were also validated using qRT-PCR.

Results

Carvacrol content in ‘Zagheh-11’ (26.13%) was approximately 23 times higher than ‘Malayer-21’ (1.12%). Reciprocally, about 10% higher thymol was found in ‘Malayer-21’ (62.15%). Moreover, the concentrations of three major triterpenic acids in ‘Zagheh-11’ were approximately as twice as those found in ‘Malayer-21’. Transcriptome analysis revealed a total of 1840 unigenes that were differentially expressed, including terpene synthases, cytochrome P450, and terpenoid backbone genes. Several differentially expressed transcription factors (such as MYB, bZIP, HB-HD-ZIP, and WRKY families) were also identified. These results suggest that an active cytosolic mevalonate (MVA) pathway may be linked to higher levels of sesquiterpenes, triterpenic acids, and carvacrol in ‘Zagheh-11’. The chloroplastic pathway of methyl erythritol phosphate (MEP) may have also contributed to a higher accumulation of thymol in Malayer-21. Indeed, ‘Zagheh-11’ showed higher expression of certain genes (HMGR, CYP71D180, β-amyrin 28-monooxygenase, and sesquiterpene synthases) in the MVA pathway, while some genes in the MEP pathway (including DXR, ispG, and γ-terpinene synthase) were distinctly expressed in Malayer-21. Future efforts in metabolic engineering of MVA/MEP pathways may benefit from these findings to produce increased levels of desired secondary metabolites at commercial scale.
Ensemble species distribution modeling and multilocus phylogeography provide insight into the spatial genetic patterns and distribution dynamics of a keystone forest species, Quercus glauca
Authors: Song Ying , Xu Gang-Biao , Long Ke-Xin , Wang Chun-Cheng , Chen Ran , Li He , Jiang Xiao-Long , Deng Min
Published: March 2024

Background

Forests are essential for maintaining species diversity, stabilizing local and global climate, and providing ecosystem services. Exploring the impact of paleogeographic events and climate change on the genetic structure and distribution dynamics of forest keystone species could help predict responses to future climate change. In this study, we combined an ensemble species distribution model (eSDM) and multilocus phylogeography to investigate the spatial genetic patterns and distribution change of Quercus glauca Thunb, a keystone of East Asian subtropical evergreen broad-leaved forest.

Results

A total of 781 samples were collected from 77 populations, largely covering the natural distribution of Q. glauca. The eSDM showed that the suitable habitat experienced a significant expansion after the last glacial maximum (LGM) but will recede in the future under a general climate warming scenario. The distribution centroid will migrate toward the northeast as the climate warms. Using nuclear SSR data, two distinct lineages split between east and west were detected. Within-group genetic differentiation was higher in the West than in the East. Based on the identified 58 haplotypes, no clear phylogeographic structure was found. Populations in the Nanling Mountains, Wuyi Mountains, and the southwest region were found to have high genetic diversity.

Conclusions

A significant negative correlation between habitat stability and heterozygosity might be explained by the mixing of different lineages in the expansion region after LGM and/or hybridization between Q. glauca and closely related species. The Nanling Mountains may be important for organisms as a dispersal corridor in the west-east direction and as a refugium during the glacial period. This study provided new insights into spatial genetic patterns and distribution dynamics of Q. glauca.
Associations between social networks, cognitive function, and quality of life among older adults in long-term care
Authors: Dodds Laura , Brayne Carol , Siette Joyce
Published: March 2024

Background

Having rich social networks is associated with better physical and cognitive health, however older adults entering long-term care may experience an increased risk of social isolation and consequent negative impacts on cognitive function. Our study aimed to identify if there is an association between accessing specific types of services or activities within long-term care on social networks and cognition.

Methods

A cross-sectional study of 96 residents from 2 aged care providers in New South Wales, Australia. Residents were given a battery of assessments measuring social network structure (Lubben Social Network Scale, LSNS-12), quality of life (EuroQol 5D, Eq. 5D5L) and cognitive function (Montreal Cognitive Assessment, MoCA). Demographic factors and service use factors were also collected from aged care providers’ electronic records. Independent sample t-test, ANOVA and linear regression analyses were used to explore associated factors for cognition.

Results

Residents had a mean age of 82.7 ± 9.4 years (median = 81) and 64.6% were women. Most residents had cognitive impairment (70.8%) and reported moderate sized social networks (26.7/60) (Lubben Social Network Scale, LSNS-12). Residents who had larger social networks of both family and friends had significantly better cognitive performance. Service type and frequency of attendance were not associated with cognitive function.

Conclusions

Among individuals most at risk of social isolation, having supportive and fulfilling social networks was associated with preserved cognitive function. The relationship between service provision and social interactions that offer psychosocial support within long-term facilities and its impact over time on cognitive function requires further exploration.
Persistent high sepsis-induced coagulopathy and sequential organ failure assessment scores can predict the 28-day mortality of patients with sepsis: A prospective study
Authors: Li Junyu , Liu Huizhen , Wang Na , Wang Fengrong , Shang Na , Guo Shubin , Wang Guodong
Published: March 2024

Background

The performance of the sepsis-induced coagulopathy (SIC) and sequential organ failure assessment (SOFA) scores in predicting the prognoses of patients with sepsis has been validated. This study aimed to investigate the time course of SIC and SOFA scores and their association with outcomes in patients with sepsis.

Methods

This prospective study enrolled 209 patients with sepsis admitted to the emergency department. The SIC and SOFA scores of the patients were assessed on days 1, 2, and 4. Patients were categorized into survivor or non-survivor groups based on their 28-day survival. We conducted a generalized estimating equation analysis to evaluate the time course of SIC and SOFA scores and the corresponding differences between the two groups. The predictive value of SIC and SOFA scores at different time points for sepsis prognosis was evaluated.

Results

In the non-survivor group, SIC and SOFA scores gradually increased during the first 4 days (P < 0.05). In the survivor group, the SIC and SOFA scores on day 2 were significantly higher than those on day 1 (P < 0.05); however, they decreased on day 4, dropping below the levels observed on day 1 (P < 0.05). The non-survivors showed higher SIC scores on days 2 (P < 0.05) and 4 (P < 0.001) than the survivors, whereas no significant differences were found between the two groups on day 1 (P > 0.05). The performance of SIC scores on day 4 for predicting mortality was more accurate than that on day 2, with areas under the curve of 0.749 (95% confidence interval [CI]: 0.674–0.823), and 0.601 (95% CI: 0.524–0.679), respectively. The SIC scores demonstrated comparable predictive accuracy for 28-day mortality to the SOFA scores on days 2 and 4. Cox proportional hazards models indicated that SIC on day 4 (hazard ratio [HR] = 3.736; 95% CI: 2.025–6.891) was an independent risk factor for 28-day mortality.

Conclusions

The time course of SIC and SOFA scores differed between surviving and non-surviving patients with sepsis, and persistent high SIC and SOFA scores can predict 28-day mortality.
Radiogenomic analysis of ultrasound phenotypic features coupled to proteomes predicts metastatic risk in primary prostate cancer
Authors: Fu Qihuan , Luo Li , Hong Ruixia , Zhou Hang , Xu Xinzhi , Feng Yujie , Huang Kaifeng , Wan Yujie , Li Ying , Gong Jiaqi , Le Xingyan , Liu Xiu , Wang Na , Yuan Jiangbei , Li Fang
Published: March 2024

Background

Primary prostate cancer with metastasis has a poor prognosis, so assessing its risk of metastasis is essential.

Methods

This study combined comprehensive ultrasound features with tissue proteomic analysis to obtain biomarkers and practical diagnostic image features that signify prostate cancer metastasis.

Results

In this study, 17 ultrasound image features of benign prostatic hyperplasia (BPH), primary prostate cancer without metastasis (PPCWOM), and primary prostate cancer with metastasis (PPCWM) were comprehensively analyzed and combined with the corresponding tissue proteome data to perform weighted gene co-expression network analysis (WGCNA), which resulted in two modules highly correlated with the ultrasound phenotype. We screened proteins with temporal expression trends based on the progression of the disease from BPH to PPCWOM and ultimately to PPCWM from two modules and obtained a protein that can promote prostate cancer metastasis. Subsequently, four ultrasound image features significantly associated with the metastatic biomarker HNRNPC (Heterogeneous nuclear ribonucleoprotein C) were identified by analyzing the correlation between the protein and ultrasound image features. The biomarker HNRNPC showed a significant difference in the five-year survival rate of prostate cancer patients (p < 0.0053). On the other hand, we validated the diagnostic efficiency of the four ultrasound image features in clinical data from 112 patients with PPCWOM and 150 patients with PPCWM, obtaining a combined diagnostic AUC of 0.904. In summary, using ultrasound imaging features for predicting whether prostate cancer is metastatic has many applications.

Conclusion

The above study reveals noninvasive ultrasound image biomarkers and their underlying biological significance, which provide a basis for early diagnosis, treatment, and prognosis of primary prostate cancer with metastasis.
Development and validation of a novel preoperative clinical model for predicting lymph node metastasis in perihilar cholangiocarcinoma
Authors: Mao Shuqi , Shan Yuying , Yu Xi , Yang Yong , Wu Shengdong , Lu Caide
Published: March 2024

Backgroud

We aimed to develop a novel preoperative nomogram to predict lymph node metastasis (LNM) in perihilar cholangiocarcinoma (pCCA) patients.

Methods

160 pCCA patients were enrolled at Lihuili Hospital from July 2006 to May 2022. A novel nomogram model was established to predict LNM in pCCA patients based on the independent predictive factors selected by the multivariate logistic regression model. The precision of the nomogram model was evaluated through internal and external validation with calibration curve statistics and the concordance index (C-index). Receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were used to evaluate and determine the clinical utility of the nomogram.

Results

Multivariate logistic regression demonstrated that age (OR = 0.963, 95% CI: 0.930–0.996, P = 0.030), CA19-9 level (> 559.8 U/mL vs. ≤559.8 U/mL: OR = 3.162, 95% CI: 1.519–6.582, P = 0.002) and tumour diameter (OR = 1.388, 95% CI: 1.083–1.778, P = 0.010) were independent predictive factors of LNM in pCCA patients. The C-index was 0.763 (95% CI: 0.667–0.860) and 0.677 (95% CI: 0.580–0.773) in training cohort and validation cohort, respectively. ROC curve analysis indicated the comparative stability and adequate discriminative ability of nomogram. The sensitivity and specificity were 0.820 and 0.652 in training cohort and 0.704 and 0.649 in validation cohort, respectively. DCA revealed that the nomogram model could augment net benefits in the prediction of LNM in pCCA patients.

Conclusions

The novel prediction model is useful for predicting LNM in pCCA patients and showed adequate discriminative ability and high predictive accuracy.
Visual outcome of various dose of glucocorticoids treatment in nonarteritic anterior ischemic optic neuropathy– a retrospective analysis
Authors: Zhao Fang-Fang , Chen Yun , Li Tai-Ping , Wang Yun , Lin Hong-Jie , Yang Jian-Feng , Chen Lan , Tan Shao-Ying , Liang Jia-Jian , Cen Ling-Ping
Published: March 2024

Background and purpose

The objective of this investigation was to assess the therapeutic efficacy of distinct glucocorticoid therapy dosages in the management of acute nonarteritic anterior ischemic optic neuropathy (NAION).

Materials and methods

This retrospective, unmasked, and non-randomized study included a total of 85 patients. The patients were categorized into four groups: Group 1 (control) consisted of 15 patients who did not receive glucocorticoids, Group 2 included 16 patients administered with oral prednisone at a dosage of 1 mg/kg/d for 14 days, Group 3 comprised 30 patients who received 250 units of methylprednisolone once daily for 3 days, followed by oral prednisone at a dosage of 1 mg/kg/d for 11 days, and Group 4 encompassed 24 patients who received 500 units of methylprednisolone once daily for 3 days, followed by oral prednisone at a dosage of 1 mg/kg/d for 11 days. The best-corrected visual acuity (BCVA) was assessed at baseline and the final follow-up (> 7 days post-treatment). The changes in visual acuity between baseline and the 7–14 day follow-up, as well as between baseline and the concluding appraisal, were employed as metrics for assessing the extent of visual enhancement.

Results

No significant differences were noted in the final visual outcomes or in the changes between final visual acuity and baseline across the four groups. In Group 1 (control), the best-corrected visual acuity (BCVA) remained unchanged during final follow-ups compared to baseline. Conversely, the intervention groups exhibited statistically significant enhancements in BCVA during final follow-up (p = 0.012, p = 0.03, and p = 0.009 for Group 2, Group 3, and Group 4, respectively) when compared to baseline. During the 7–14 day follow-up, there was a significant difference in the changes between baseline BCVA and follow-up BCVA across the groups (p = 0.035). Go a step further by Bonferroni correction for multiple comparisons, group 4 showed a greater change in vision compared with group1 (p = 0.045).

Conclusion

Our study on acute nonarteritic anterior ischemic optic neuropathy (NAION) showed no significant final visual outcome differences. Nevertheless, Groups 2, 3, and 4 demonstrated improved best-corrected visual acuity (BCVA) during the final follow-up. Notably, a 500-unit dose of methylprednisolone resulted in short-term BCVA enhancement. This suggests potential consideration of 500 units of methylprednisolone for short-term NAION vision improvement, despite its limited long-term impact.
Determinants and outcomes of health-promoting lifestyle among people with schizophrenia
Authors: Fan Yu , Zhou Liang , Chen Xiyuan , Su Jinghua , Zhong Shaoling
Published: March 2024

Background

Healthy lifestyle is an important protective factor of developing cardiovascular disease in people with schizophrenia. However, little is known about the determinants of lifestyle and its contribution to metabolic syndrome. This study aimed to explore the influencing factors of health-promoting lifestyle (HPL) and its association with metabolic syndrome among people with schizophrenia.

Methods

A cross-sectional study was conducted in twenty-two primary health centers of Guangzhou, China between December 2022 and April 2023. A total of 538 patients with schizophrenia were recruited through convenience sampling. Self-administered scales, questionnaires, and clinical data were collected. Scales and questionnaires included social-demographic information, Health-Promoting Lifestyles Profile (HPLP-C), UCLA Loneliness Scale (ULS), and International Physical Activity Questionnaire-Short Form (IPAQ-SF). Cluster analyses were used to divide participants into two groups based on the distribution characteristics of HPLP-C scores. Logistic regression models were used to identify factors associated with HPL and the association between HPL and metabolic syndrome.

Results

There were 271 participants in the high HPL group and 267 participants in the low HPL group. Logistic regression analysis revealed that loneliness posed a risk factor for high HPL, while high education and moderate-vigorous physical activity served as protective factors for high HPL. Low HPL was a risk factor for the prevalence of metabolic syndrome.

Conclusions

Promotion of high education literacy and a physically active lifestyle should be priority targets in the health management of schizophrenia. Primary healthcare providers can play a pivotal role in assisting patients to mitigate metabolic syndrome by reinforcing healthy lifestyle strategies.
Prevalence and risk factors for diabetic foot complications among people living with diabetes in Harare, Zimbabwe: a cross-sectional study
Authors: Kuguyo Oppah , Mukona Doreen Macherera , Chikwasha Vasco , Gwanzura Lovemore , Chirenda Joconiah , Matimba Alice
Published: March 2024

Background

Diabetic foot disease (DF) is a common diabetes-related complication; however, the prevalence and associated risk factors for DF are not well characterised among people living with diabetes (PLWD) in Zimbabwe. This may suggest the unavailability of adequate strategies to diagnose and treat DF in the country. This study aimed to determine the prevalence of DF and associated risk factors for PLWD in Harare, Zimbabwe.

Methods

This was a cross-sectional study, employing a quantitative approach. In total, 352 PLWD were recruited from 16 primary care clinics in Harare. Sociodemographic and clinical data were collected via face-to-face interviews and clinical records reviews. The DF screening included an evaluation for peripheral neuropathy, ankle-brachial index (ABI), ulceration, and amputation. Self-administered questionnaires were used to assess knowledge, attitudes, and practices (KAPs), and KAP was scored using Bloom’s cut-off. Chi-Square goodness-of-fit tests were performed, and regression analyses were used for association analysis. The threshold for significance wasp < 0.05.

Results

This group included 82 men and 279 women, with a combined mean age of 57.9 ± 14 years. Twenty one (~ 26%) men and 41 (15%) women had type 1 diabetes. The diabetes type distribution significantly differed by gender (p < 0.001). Oral hypoglycaemics (71%) were most commonly administered for management. DF was observed in 53% (95% CI = 50–56) of PLWD. Other DF symptoms observed were abnormal ABI (53%), peripheral neuropathy (53%), foot ulceration (17%) and amputation (3%). Peripheral neuropathy increased the risk of ulceration (OR = 1.7; 95% CI = 1.1–2.6; p = 0.019), while insulin use was protective against amputation (OR = 0.1; 95% CI = 0.1–0.9;p = 0.049). Most (87%) of the participants demonstrated good DF knowledge and the importance of adhering to medication to prevent DF. However, 96% did not know that smoking was a risk factor for DF. Nearly two-thirds (63%) demonstrated poor attitudes and practices. Poor attitudes and practices were not predictors of DF ulceration risk (p > 0.05).

Conclusion

This study showed that there was a high prevalence of DF (53%) in PLWD in Zimbabwe, and insulin use was protective against DF. There is an urgent need for policy revisions to include foot screening in routine primary care and increasing insulin use for PLWD to prevent complications such as DF as an integral part of primary care.
Identifying determinants of varenicline adherence using the Theoretical Domains framework: a rapid review
Authors: Minian Nadia , Wong Melissa , Hafuth Sowsan , Rodak Terri , Rahimi Alma , Gjomema Dea , Rose Jonathan , Zawertailo Laurie , Ratto Matt , Selby Peter
Published: March 2024

Background

Adhering to varenicline has been shown to significantly improve the chances of successfully quitting smoking, with studies indicating a twofold increase in 6-month quit rates. However, despite its potential benefits, many individuals struggle with maintaining good adherence to varenicline; thus there is a need to develop scalable strategies to help people adhere. As a first step to inform the development of an intervention to improve adherence to varenicline, we conducted a rapid literature review to identify: 1) modifiable barriers and facilitators to varenicline adherence, and 2) behaviour change techniques associated with increased adherence to varenicline.

Methods

We searched MEDLINE, Embase, APA PsycINFO, CINAHL, and the Cochrane Central Register of Controlled Trials for relevant studies published between 2006 and 2022. Search terms included “varenicline,” “smoking cessation,” and "adherence," and their respective subject headings and synonyms. We screened and included studies reporting modifiable determinants of adherence to varenicline and then assessed quality, extracted modifiable determinants and mapped them to the Theoretical Domains Framework version 2 and the Behaviour Change Technique Taxonomy version 1.

Results

A total of 1,221 titles were identified through the database searches; 61 met the eligibility criteria. Most of the studies were randomized controlled trials and predominantly focused on barriers to varenicline. Only nine studies explicitly mentioned behaviour change techniques used to help varenicline adherence. Eight domains were identified as barriers to varenicline adherence (behavioural regulation, memory, goals, intentions, beliefs about capabilities, beliefs about consequences, optimism/pessimism, and environmental context) and five as facilitators (knowledge, behavioural regulation, beliefs about capabilities, social influences, and environmental context).

Conclusions

This study identifies barriers and facilitators that should be addressed when developing a complex adherence intervention tailored to patients’ needs based on modifiable determinants of medication adherence, some of which are under- used by existing adherence interventions. The findings from this review will inform the design of a theory-based healthbot planned to improve varenicline adherence in people undergoing smoking cessation treatment.

Systematic review registration

This study was registered with PROSPERO (# CRD42022321838).
Exploring determinants of sex and family history-based disparity in type 2 diabetes mellitus prevalence among clinical patients
Authors: Alrashed Fahad Abdulaziz , Iqbal Muhammad , Alsubiheen Abdulrahman M , Ahmad Tauseef
Published: March 2024

Background

Type 2 diabetes mellitus represents a multifaceted disorder characterized by intricate pathophysiological mechanisms, encompassing diminished insulin secretion, augmented hepatic glucose production, and heightened insulin resistance. This study aims to assess the sex (Male and Female only) and family history-based differences in the prevalence of T2DM and explore the determinants contributing to this disparity among clinical patients.

Subjects and methods

The study encompassed a diverse pool of clinical patients, encompassing both individuals with diabetes and those without the condition, who had previously sought medical attention for clinical checkups at healthcare centers. The collected data included essential parameters such as blood pressure, weight, height, smoking habits, educational background, and physical activity levels. To ensure methodological rigor and data accuracy, blood pressure measurements adhered to the stringent guidelines set forth by the World Health Organization.

Results

Participants of the present study reported diabetes, among which notable findings emerged regarding health indicators. It was observed that the prevalence of high blood pressure, obesity, and high blood cholesterol exhibited a statistically significant increase among the female participants, underscoring the sex-based disparities in these health parameters. The male population aged 60 or older, the presence of a family history of DM accentuated this risk, resulting in a striking 3.1 times higher prevalence compared to females, who exhibited a 2.4 times higher risk (OR = 2.4,p = 0.0008). This intriguing relationship between diabetes and cholesterol levels was not limited to sex. Both male (OR = 2.47) and female (OR = 2.1) diabetes patients displayed highly significant associations with cholesterol levels. The risk of T2DM was significantly associated with triglycerides in both sexes (1.58 times higher in males, and 1.71 times higher in females).

Conclusions

The significance of hypertension as a comorbidity in T2DM, highlighting sex-specific associations and the potential impact of a family history of diabetes on blood pressure. Our findings emphasize the importance of considering lipid profiles, obesity, and their sex-specific associations when assessing and managing diabetes risk. Comprehensive diabetes care should include strategies for lipid control, weight management, and cardiovascular risk reduction, tailored to the individual’s sex and specific risk profile.
Correlation of geopolitics, education, democracy with COVID-19 vaccination rate
Authors: Chakhunashvili Konstantine , Chakhunashvili Davit G. , Kvirkvelia Eka , Toria Tornike , Basilaia Liza , Gorjomeladze Tsira
Published: March 2024

Introduction

Vaccine hesitancy is an ongoing problem and determining the factors that increase the vaccination rate in various countries of the world might be useful for further implementation of efficient public health policies and negating anti-vaccination campaigns.

Materials and methods

Human Development Index (HDI), Education Index (EI), Democracy Index (DI), COVID-19 vaccination rates, COVID-19 data were collected from public sources such as UNDP - Human Development Reports, UNESCO - Education Index, Economist Intelligence, WHO– COVID-19 Dashboard, Our World In Data, The Financial Times COVID-19 Dashboard. Statistical analysis such as Pearson correlation, and linear regression analyses were done to determine a relation between the above-mentioned indices and COVID-19 vaccination rates (1-dose, 2-dose, booster, and combined).

Results

HDI had the strongest positive correlation with the vaccination rates (1-dose– r (181) = 0.632, p < 0.001, 2-dose– r (181) = 0.671, p < 0.001, booster– r (181) = 0.718, p < 0.001, combined– 0.703, p < 0.001). EI (1-dose– r (177) = 0.560, p < 0.001, 2-dose– r (177) = 0.599, p < 0.001, booster– r (177) = 0.642, p < 0.001, combined– 0.626, p < 0.001), DI (1-dose– r (163) = 0.445, p < 0.001, 2-dose– r (163) = 0.479, p < 0.001, booster– r (163) = 0.534, p < 0.001, combined– 0.508, p < 0.001), as well as Geographic location (1-dose– η (Eta) = 0.610 p < 0.001, 2-dose– η (Eta) = 0.633 p < 0.001, booster– η (Eta) = 0.657, p < 0.001, combined– η (Eta) = 0.645, p < 0.001) had positive correlation with vaccination rates.

Conclusion

There is a strong positive correlation of COVID-19 vaccination rates with HDI and EI.
Development and validation of the physician self-efficacy to manage emotional challenges Scale (PSMEC)
Authors: Weurlander Maria , Wänström Linda , Seeberger Astrid , Lönn Annalena , Barman Linda , Hult Håkan , Thornberg Robert , Wernerson Annika
Published: March 2024

Background

Medical students experience emotional challenges during their undergraduate education, often related to work-based learning. Consequently, they may experience feelings of uncertainty and self-doubt, which can negatively affect their well-being. Therefore, it is crucial to support students’ development of their ability to manage distressful situations. Self-efficacy beliefs may be a central aspect of supporting them in this development, and have been shown to relate to resilient factors such as students’ motivation, learning, and well-being.

Methods

We constructed a scale to measure medical students’ physician self-efficacy to manage emotional challenges during work-based learning, the PSMEC scale. The aim of the present study was to evaluate some of the psychometric properties of the PSMEC scale. The scale consists of 17 items covering five subscales: (1) medical knowledge and competence, (2) communication with difficult patients and delivering bad news, (3) being questioned and challenged, (4) educative competence in patient encounters, and (5) ability to establish and maintain relationships with healthcare professionals. Data were collected from 655 medical students from all seven medical schools in Sweden. To investigate the scale’s dimensionality and measurement invariance with regard to gender and time in education, single and multiple group confirmatory factor models were estimated using techniques suitable for ordered categorical data. Measures of Cronbach’s alpha were calculated to evaluate internal consistency.

Results

The scale showed good internal consistency on both the global dimension and the five subdimensions of self-efficacy. In addition, the scale was shown to be measurement invariant across genders and times in education, indicating that the scale means of male and female medical students and the scale means of students at the middle and end of their education can be compared.

Conclusions

The physician self-efficacy to manage emotional challenges scale demonstrated satisfactory psychometric properties, with regards to dimensionality, internal consistency, and measurement invariance relating to gender and time in education, and this study supports the usefulness of this scale when measuring self-efficacy in relation to emotional challenges.
Comparison of gamification and role-playing education on nursing students’ cardiopulmonary resuscitation self-efficacy
Authors: Khaledi Ata , Ghafouri Raziyeh , Anboohi Sima Zohari , Nasiri Malihe , Ta’atizadeh Mohsen
Published: March 2024

Background

Cardiopulmonary resuscitation (CPR) is one of the most fundamental skills a nursing student should be trained in. Gamification in education involves using game elements to increase motivation, engagement, and personalization of the learning process. The gamification method creates competition among students using various methods, comparing to the role-playing method which is a teaching method that allows individuals to actively engage in simulated scenarios. Therefore, this research aimed to compare the effect of CPR education using gamification and role-playing on the self-efficacy of nursing students.

Methods

This research was a quasi-experimental intervention type with three groups. A total of 154 nursing students participated in this study and were divided into intervention with role-playing (n = 53), gamification (n = 60) and conventional (lecture) (n = 41) groups. In the conventional method, CPR skills were taught to students using practical exercises. In the role-playing method, after training with moulages, a scenario was presented, and students were assigned roles. In the gamification method, after training with moulages, a scenario was presented, and after that, Kahoot software was used to create a sense of competition and excitement in the game. Self-efficacy scores were measured before and after interventions. Self-efficacy in CPR, knowledge, and skills of nursing students in CPR were assessed in each of the three groups using The Basic Resuscitation Skills Self- Efficacy Scale.

Results

In the present study, 154 nursing students, including 92 females and 62 males, participated. There was a statistically significant difference in the mean self-efficacy scores before and after training in both the gamification and role-playing groups (P < 0.05). There was a statistically significant difference in the mean self-efficacy scores among the three groups (gamification, role-playing, and lecture) (P < 0.05).

Conclusion

Based on results it can be concluded that the teaching method used in CPR training affects the self-efficacy of CPR. Active methods, have a greater impact on CPR self-efficacy.
Plasma metabolites and risk of seven cancers: a two-sample Mendelian randomization study among European descendants
Authors: Chen Yaxin , Xie Yufang , Ci Hang , Cheng Zhengpei , Kuang Yongjie , Li Shuqing , Wang Gang , Qi Yawen , Tang Jun , Liu Dan , Li Weimin , Yang Yaohua
Published: March 2024

Background

While circulating metabolites have been increasingly linked to cancer risk, the causality underlying these associations remains largely uninterrogated.

Methods

We conducted a comprehensive 2-sample Mendelian randomization (MR) study to evaluate the potential causal relationship between 913 plasma metabolites and the risk of seven cancers among European-ancestry individuals. Data on variant-metabolite associations were obtained from a genome-wide association study (GWAS) of plasma metabolites among 14,296 subjects. Data on variant-cancer associations were gathered from large-scale GWAS consortia for breast (N = 266,081), colorectal (N = 185,616), lung (N = 85,716), ovarian (N = 63,347), prostate (N = 140,306), renal cell (N = 31,190), and testicular germ cell (N = 28,135) cancers. MR analyses were performed with the inverse variance-weighted (IVW) method as the primary strategy to identify significant associations at Bonferroni-corrected P < 0.05 for each cancer type separately. Significant associations were subjected to additional scrutiny via weighted median MR, Egger regression, MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO), and reverse MR analyses. Replication analyses were performed using an independent dataset from a plasma metabolite GWAS including 8,129 participants of European ancestry.

Results

We identified 94 significant associations, suggesting putative causal associations between 66 distinct plasma metabolites and the risk of seven cancers. Remarkably, 68.2% (45) of these metabolites were each associated with the risk of a specific cancer. Among the 66 metabolites, O-methylcatechol sulfate and 4-vinylphenol sulfate demonstrated the most pronounced positive and negative associations with cancer risk, respectively. Genetically proxied plasma levels of these two metabolites were significantly associated with the risk of lung cancer and renal cell cancer, with an odds ratio and 95% confidence interval of 2.81 (2.33–3.37) and 0.49 (0.40–0.61), respectively. None of these 94 associations was biased by weak instruments, horizontal pleiotropy, or reverse causation. Further, 64 of these 94 were eligible for replication analyses, and 54 (84.4%) showed P < 0.05 with association patterns consistent with those shown in primary analyses.

Conclusions

Our study unveils plausible causal relationships between 66 plasma metabolites and cancer risk, expanding our understanding of the role of circulating metabolites in cancer genetics and etiology. These findings hold promise for enhancing cancer risk assessment and prevention strategies, meriting further exploration.
Diffuse myocardial fibrosis is uncommon in people with perinatally acquired human immunodeficiency virus infection
Authors: Williams Jason L. , Hung Frances , Jenista Elizabeth , Barker Piers , Chakraborty Hrishikesh , Kim Raymond , McCrary Andrew W. , Shah Svati H. , Thielman Nathan , Bloomfield Gerald S.
Published: March 2024

Background

Cardiovascular disease (CVD) remains a leading cause of death in people living with HIV. Myocardial fibrosis is well-described in HIV infection acquired in adulthood. We evaluate the burden of fibrosis by cardiac magnetic resonance in people with perinatal HIV infection.

Methods

Individuals with perinatally acquired HIV (pnHIV) diagnosed before 10 years-old and on antiretroviral treatment for ≥ 6 months were matched with uninfected controls. Patients with significant cardiometabolic co-morbidities and pregnancy were excluded. Diffuse fibrosis was assessed by cardiac magnetic resonance (CMR) with native T1 mapping for calculation of extracellular volume fraction (ECV). Viability was assessed with late gadolinium enhancement. The normality of fibrosis was assessed using the Komogrov-Smirnov test. Fibrosis between the groups was analyzed using a Mann-Whitney U test, as the data was not normally distributed. Statistical significance was defined as a p-valve < 0.05.

Results

Fourteen adults with pnHIV group and 26 controls (71% female and 86% Black race) were assessed. The average (± standard deviation) age in the study group was 29 (± 4.3) years-old. All pnHIV had been on ART for decades. Demographic data, CMR functional/volumetric data, and pre-contrast T1 mapping values were similar between groups. Diastolic function was normal in 50% of pnHIV patients and indeterminate in most of the remainder (42%). There was no statistically significant difference in ECV between groups; p = 0.24.

Conclusion

Perinatally-acquired HIV was not associated with diffuse myocardial fibrosis. Larger prospective studies with serial examinations are needed to determine whether pnHIV patients develop abnormal structure or function more often than unaffected controls.
Multicenter analysis on the value of standard (chemo)radiotherapy in elderly patients with locally advanced adenocarcinoma of the esophagus or gastroesophageal junction
Authors: Bostel Tilman , Nikolaidou Eirini , Wollschläger Daniel , Mayer Arnulf , Kaufmann Justus , Hopprich Anne , Rühle Alexander , Grosu Anca-Ligia , Debus Jürgen , Fottner Christian , Moehler Markus , Grimminger Peter , Schmidberger Heinz , Nicolay Nils Henrik
Published: March 2024

Background

To assess the tolerability and oncological results of chemoradiation in elderly patients with locally advanced adenocarcinoma of the esophagus or gastroesophageal junction.

Methods

This multi-center retrospective analysis included 86 elderly patients (≥ 65 years) with esophageal or gastroesophageal junction adenocarcinoma (median age 73 years; range 65–92 years) treated with definitive or neoadjuvant (chemo)radiotherapy. The treatment was performed at 3 large comprehensive cancer centers in Germany from 2006 to 2020. Locoregional control (LRC), progression-free survival (PFS), distant metastasis-free survival (DMFS), overall survival (OS), and treatment-associated toxicities according to CTCAE criteria v5.0 were analyzed, and parameters potentially relevant to patient outcomes were evaluated.

Results

Thirty-three patients (38%) were treated with neoadjuvant chemoradiation followed by surgery, while the remaining patients received definitive (chemo)radiation. The delivery of radiotherapy without dose reduction was possible in 80 patients (93%). In 66 patients (77%), concomitant chemotherapy was initially prescribed; however, during the course of therapy, 48% of patients (n = 32) required chemotherapy de-escalation due to treatment-related toxicities and comorbidities. Twenty-nine patients (34%) experienced higher-grade acute toxicities and 14 patients (16%) higher-grade late toxicities. The 2-year LRC, DMFS, PFS, and OS amounted to 72%, 49%, 46%, and 52%, respectively. In multivariate analysis, neoadjuvant chemoradiation followed by surgery was shown to be associated with significantly better PFS (p = 0.006), DMFS (p = 0.006), and OS (p = 0.004) compared with all non-surgical treatments (pooled definitive radiotherapy and chemoradiation). No such advantage was seen over definitive chemoradiation. The majority of patients with neoadjuvant therapy received standard chemoradiotherapy without dose reduction (n = 24/33, 73%). In contrast, concurrent chemotherapy was only possible in 62% of patients undergoing definitive radiotherapy (n = 33/53), and most of these patients required dose-reduction or modification of chemotherapy (n = 23/33, 70%).

Conclusions

In our analysis, omission of chemotherapy or adjustment of chemotherapy dose during definitive radiotherapy was necessary for the overwhelming majority of elderly esophageal cancer patients not eligible for surgery, and hence resulted in reduced PFS and OS. Therefore, optimization of non-surgical approaches and the identification of potential predictive factors for safe administration of concurrent chemotherapy in elderly patients with (gastro)esophageal adenocarcinoma is required.