bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk factors associated with influenza A (H1N1)pdm09: a nested case control study of TB patients with ILI in Lahore District, Pakistan
Authors: Umbreen Gulshan , Rehman Abdul , Aslam Sadaf , Jabeen Chanda , Iqbal Muhammad , Riaz Aayesha , Sadiq Shakera , Maqsood Rubab , Rashid Hamad Bin , Afzal Saira , Arshad Nimra , Mushtaq Muhammad Hassan , Chaudhry Mamoona
Published: July 2024

Background

Co-morbidity with respiratory viruses including influenza A, cause varying degree of morbidity especially in TB patients compared to general population. This study estimates the risk factors associated with influenza A (H1N1)pdm09 in TB patients with ILI.

Methods

A cohort of tuberculosis (TB) patients who were admitted to and enrolled in a TB Directly Observed Therapy Program (DOTs) in tertiary care hospitals of Lahore (Mayo Hospital and Infectious Disease Hospital) were followed for 12 weeks. At the start of study period, to record influenza-like illness (ILI), a symptom card was provided to all the participants. Every participant was contacted once a week, in person. When the symptoms were reported by the participant, a throat swab was taken for the detection of influenza A (H1N1)pdm09. A nested case control study was conducted and TB patients with ILI diagnosed with influenza A (H1N1)pdm09 by conventional RT-PCR were selected as cases, while those who tested negative by conventional RT-PCR were enrolled as controls. All cases and controls in the study were interviewed face-to-face in the local language. Epidemiological data about potential risk factors were collected on a predesigned questionnaire. Logistic analysis was conducted to identify associated risk factors in TB patients with ILI.

Results

From the main cohort of TB patients (n = 152) who were followed during the study period, 59 (39%) developed ILI symptoms; of them, 39 tested positive for influenza A (H1N1)pdm09, while 20 were detected negative for influenza A (H1N1)pdm09. In univariable analysis, four factors were identified as risk factors (p < 0.05). The final multivariable model identified one risk factor (sharing of towels, P = 0.008)) and one protective factor (wearing a face mask, p = < 0.001)) for influenza A (H1N1)pdm09 infection.

Conclusion

The current study identified the risk factors of influenza A (H1N1)pdm09 infection among TB patients with ILI.
Molecular epidemiology and virulence factors of group B Streptococcus in South Korea according to the invasiveness
Authors: Choi Jae Hong , Kim Tae Hyoung , Kim Eui Tae , Kim Young Ree , Lee Hyunju
Published: July 2024

Background

Group B Streptococcus (GBS) causes invasive infections in newborns and elderly individuals, but is a noninvasive commensal bacterium in most immunocompetent people. Recently, the incidence of invasive GBS infections has increased worldwide, and there is growing interest in the molecular genetic characteristics of invasive GBS strains. Vaccines against GBS are expected in the near future. Here, we aimed to analyze the molecular epidemiology of GBS according to the invasiveness in South Korea.

Methods

We analyzed GBS isolates collected and stored in two hospitals in South Korea between January 2015 and December 2020. The invasiveness of these isolates was determined via a retrospective review of clinical episodes. Totally, 120 GBS isolates from 55 children and 65 adults were analyzed. Serotype and sequence type (ST) were determined using multiplex polymerase chain reaction (PCR) and multilocus sequence typing, respectively. Fourteen virulence factor-encoding genes of GBS were analyzed using multiplex PCR.

Results

Forty one (34.2%) were invasive infection-related GBS isolates (iGBS). The most frequently detected serotype was III (39/120, 32.5%), and it accounted for a high proportion of iGBS (21/41, 51.2%). The most frequent ST was ST19 (18/120, 15.0%), followed by ST2 (17/120, 14.2%). Serotype III/ST17 was predominant in iGBS (12/41, 29.3%), and all 17 ST2 strains were noninvasive. The distribution of most of the investigated virulence factors was not significantly related to invasiveness; noteworthily, most of the serotype III/ST17 iGBS carried pilus island (PI) 2b (10/12, 83.3%), and the prevalence of fbsB was significantly low compared with noninvasive GBS isolates (P = 0.004). Characteristically, the combination of bca(+)-cspA(+)-pavA(+)-fbsB(-)-rib(+)-bac(-) was predominant in iGBS (24.4%, 10/41).

Conclusions

Serotype III/ST17 GBS carrying PI-2b was frequently detected in iGBS. There was no significant association between invasiveness and the pattern of virulence factors; however, a specific combination of virulence factors was predominant in iGBS.
Hemoglobin, albumin, lymphocytes and platelets (HALP) score as a predictor of survival in patients with glioblastoma (GBM)
Authors: Demir Ozden , Demirag Guzin , Cakmak Furkan , Bayraktar Demet Işık , Tokmak Leman
Published: July 2024

Background

We aimed to investigate whether the HALP score was a predictor of survival in patients with Glioblastoma (GBM).

Methods

A total of 84 Glioblastoma (GBM) patients followed in our clinic were included in the study. HALP scores were calculated using the preoperative hemoglobin, albumin, lymphocyte and platelet results of the patients. For the HALP score, a cut-off value was found by examining the area below the receiver operating characteristic (ROC) curve. Patients were divided into two groups as low and high according to this cut-off value. The relationships among the clinical, dermographic and laboratory parameters of the patients were examined using these two groups.

Results

Median OS, PFS, HALP score, NLR, PLR were 15 months (1.0–78.0), 8 months (1.0–66.0), 37.39 ± 23.84 (min 6.00-max 132.31), 4.14, 145.07 respectively. A statistically significant correlation was found between HALP score and OS, PFS, NLR, PLR, ECOG-PS status using Spearman’s rho test (p = 0.001, p < 0.001, p < 0.001, p < 0.001, p = 0.026 respectively). For the HALP score, a cut-off value of = 37.39 (AUC = 0.698, 95% CI, p < 0.002) was found using ROC analysis. Median OS was 12 (6.99–17.01) months in the low HALP group and 21 (11.37–30.63) months in the high HALP group (p = 0.117). NLR and PLR were significantly lower in the HALP high group (p < 0.001, p < 0.001 respectively). The ratio of receiving treatment was significantly higher in the high HALP group (p < 0.05). In Multivariate analysis, significant results were found for treatment status and ECOG-PS status (p < 0.001, p = 0.038 respectively).

Conclusions

The HALP score measured at the beginning of treatment seems to have predictive importance in the prognosis of GBM patients. A HALP score of > 37.39 was associated with prolonged survival in high-grade brain tumors.
The association between dietary, physical activity and the DNA methylation of PPARGC1A, HLA-DQA1 and ADCY3 in pregnant women with gestational diabetes mellitus: a nest case-control study
Authors: Wang Yan , Ren Jianhua , Luo Biru
Published: July 2024

Background

Gestational diabetes mellitus (GDM) is associated with DNA methylation and lifestyle. The effects of DNA methylation on GDM, and the interaction between DNA methylation and lifestyle factors are not well elucidated. The objective of this study was to explore the association between GDM, DNA methylation and lifestyle factors.

Methods

A nest case-control design was performed. Sociodemographic data, dietary intake and daily physical activity information of pregnant women were collected. Bisulfate pyrosequencing was used to detect the DNA methylation level of PPARGC1A, HLA-DQA1, and ADCY3 genes. The differences of DNA methylation levels between the GDM group and the control group were compared. The correlation between clinical characteristics, dietary, physical activity and DNA methylation level was analyzed.

Results

A total of 253 pregnant women were enrolled, of which, 60 participants (GDM: 30; control: 30) were included in the final analysis. There were no significant differences in DNA methylation levels of six methylated sites between the two groups in this study (P > 0.05). Daily intake of potato and poultry were associated with DNA methylation level of the CpG 1 site of the ADCY3 gene in all participants and the control group (P < 0.05). Duration of folic acid intake before pregnancy was correlated with the methylation level of the CpG 1 site of the ADCY3 gene in all participants (r = 0.341, P = 0.04) and the control group (r = 0.431, P = 0.025). Daily oil intake was correlated with the methylation level of CpG 2 (r = 0.627, P = 0.016) and CpG 3 (r = 0.563, P = 0.036) of PPARGC1A in the GDM group.

Conclusion

The association between the DNA methylation levels and GDM wasn’t validated. There were associations between dietary and DNA methylation in pregnant women. A large-sample-sized and longitudinal study is warranted to further investigate the impacts of lifestyle on DNA methylation.
Early intervention in Hirschsprung’s disease: effects on enterocolitis and surgical outcomes
Authors: Zhang Yunhan , Xiang Xiao , Li Xunfeng , Feng Wei , Guo Zhenhua
Published: July 2024

Background

The timing of surgical intervention for Hirschsprung’s disease (HSCR) has been a topic of continued discussion. The objective of this study was to evaluate the significance of age at surgery in the management of HSCR by conducting a comparative analysis of the correlation between surgical age and midterm outcomes.

Methods

We conducted a retrospective analysis of children with HSCR who underwent one-stage laparoscopic assisted pull-through surgery with modified Swenson technology at our hospital between 2015 and 2019. The study population was stratified into two groups based on surgical age: patients who underwent surgery within a period of less than 3 months and those who underwent surgery between 3 and 12 months. The basic conditions, complications at 3–7 years after surgery, anal function (Rintala scale) and quality of life (PedsQLTM4.0) were compared between the groups.

Results

A total of 235 children (196 males and 39 females) were included in the study. No statistically significant differences in postoperative bowel function (P = 0.968) or quality of life (P = 0.32) were found between the two groups. However, there was a significant reduction in the incidence of Hirschsprung-associated enterocolitis (HAEC) among individuals under the age of three months prior to undergoing surgical intervention (69.1%) compared to the incidence observed postsurgery (30.9%). This difference was statistically significant (P < 0.001).

Conclusion

In the current study, the age at which surgery was performed did not exhibit a discernible inclination towards influencing mid-term anal function or quality of life. Early surgical intervention can effectively diminish the occurrence of HAEC, minimize the extent of bowel resection, and expedite the duration of the surgical procedure.
“It’s changing our lives, not for the better. It’s important that we have a say”. The role of young people in informing public health and policy decisions about gambling marketing
Authors: Pitt Hannah , McCarthy Simone , Randle Melanie , Arnot Grace , Daube Mike , Thomas Samantha
Published: July 2024

Background

Marketing has a significant impact on the normalisation of gambling for youth across the globe. This has included shaping positive attitudes towards gambling, as well as increasing the social and cultural acceptance of gambling – particularly aligned with valued activities such as sport. Because of this, public health experts argue that gambling marketing poses a significant risk to the health and wellbeing of youth. While young people are increasingly exposed to, and impacted by marketing for gambling products, they are rarely consulted about policy issues and options. This study aimed to explore young Australians’ perceptions of current policy responses to gambling advertising, whether they thought young people should be involved in discussions and decisions about gambling marketing regulations, and their perceptions of the duty of governments to protect young people from gambling industry marketing strategies.

Methods

Qualitative focus groups (n = 22) were held with n = 64, 12–17 year olds in the Australian states of Victoria and New South Wales. Participants were asked to reflect on current gambling policies, particularly relating to marketing, what they thought should be done about gambling marketing, and if and how young people should be included in public health responses to gambling. An interpretivist ‘Big Q’ approach to reflexive thematic analysis was used.

Results

Young people highlighted the need for more effective regulations around the content and frequency of gambling marketing. They also wanted to see more realistic representations of the negative impacts of gambling to counter persistent positive commercial marketing messages. Most thought that young people should be given an opportunity to have a say about responses to gambling due to their unique experiences. Participants identified mechanisms to increase young people’s engagement in decision making, such as direct lines of communication to different levels of government, involvement in research, and diversifying ways of engagement. Specific recommendations included more regulatory action such as bans on gambling advertising.

Conclusions

Creating formal structures that facilitate the inclusion of young people’s perspectives in decisions made about gambling can result in more innovative and effective strategies to prevent the harms from gambling industry products, promotions, and practices.
Validity of the Chinese multimorbidity-weighted index in measuring disease burden using health check-ups data in primary care
Authors: Lai Ying-Si , Gao Xin-Yuan , Hu Wei-Hua , Liu Yi-Xuan , Zhang Yong-Jin , Liu Jia-Cong , Yang Chun , Liao Jing
Published: July 2024

Background

As multimorbidity becomes common that imposes a considerable burden to patients, but the extent to which widely-used multimorbidity indexes can be applied to quantify disease burden using primary care data in China is not clear. We applied the Chinese Multimorbidity-Weighted Index (CMWI) to health check-ups data routinely collected among older adults by primary care, to examine its validity in measuring multimorbidity associated risks of disability and mortality in annual follow-ups.

Methods

The study utilized data from annual health check-ups of older adults, which included information on individual age, sex, and 14 health conditions at primary care in a district of Guangzhou, Guangdong, China. The risk of CMWI for mortality was analysed in a total sample of 45,009 persons 65 years and older between 2014 and 2020 (average 2.70-year follow-up), and the risk for disability was in a subsample of 18,320 older adults free of physical impairment in 2019 and followed-up in 2020. Risk of death and disability were assessed with Cox proportional hazard regression and binary logistic regression, respectively, with both models adjusted for age and sex variables. The model fit was assessed by the Akaike information criterion (AIC), and C-statistic or the area under the receiver operating characteristic curve (AUC).

Results

One unit increase in baseline-CMWI (Median= 1.70, IQR: 1.30-3.00) was associated with higher risk in subsequent disability (OR = 1.12, 95%CI = 1.05,1.20) and mortality (OR = 1.18, 95%CI = 1.14, 1.22). Participants in the top tertile of CMWI had 99% and 152% increased risks of disability and mortality than their counterparts in the bottom tertile. Model fit was satisfied with adequate AUC (0.84) or C-statistic (0.76) for both outcomes.

Conclusions

CMWI, calculated based on primary care’s routine health check-ups data, provides valid estimates of disability and mortality risks in older adults. This validated tool can be used to quantity and monitor older patients’ health risks in primary care.
Association of vision and hearing impairment and dietary diversity among the oldest old in China: findings from the Chinese longitudinal healthy longevity survey
Authors: Shen Xinyue , Chen Xuhao , Chen Xiaohong , Li Zhidong , Lin Junxiong , Huang Haishun , Xie Rui , Li Yiqing , Zhu Yingting , Zhuo Yehong
Published: July 2024

Background

The presence of sensory impairment among older age cohorts exerts a significant impact on both individuals and society generally. Although the impact of dietary patterns on health is vital across all stages of life, there still a paucity of comprehensive research on the association between dietary variety and sensory impairments.

Objective

To investigate the potential relationship between dietary diversity and the prevalence of visual and hearing impairment or dual sensory impairments (visual and hearing impairment) among the oldest old population.

Methods

This is a cross-sectional study relied on data obtained from the 2018 survey conducted by the Chinese Longitudinal Healthy Longevity Survey (CLHLS). Subjects aged 80 and older with complete vision and hearing data were included in the study. Multivariate logistic regression models were developed to examine the association between dietary components and visual and hearing impairment while controlling for age, gender, socioeconomic demographic factors, living habits, other food habits, and general health status.

Results

The study included 10,093 participants, with an average age of 92.29 ± 7.75 years. Vision and hearing function were assessed based on the ability to distinguish the direction of the break in the circle and the requirement for hearing aids, respectively. Upon controlling for confounding variables, individuals with a greater Dietary Diversity Score (DDS, the number of food groups, range: 1–11) had a reduced likelihood of experiencing visual impairment (odds ratio [OR] = 0.944, 95% confidence interval [CI], 0.915—0.974) and dual sensory impairment (OR = 0.930, 95% CI, 0.905—0.955). In comparison to the low dietary variety group (insufficient dietary diversity, DDS < 4), the high dietary diversity group (sufficient dietary diversity, DDS ≥ 4) exhibited a decreased risk of visual impairment (OR = 0.820, 95% CI, 0.713—0.944) and dual sensory impairment (OR = 0.751, 95% CI, 0.667—0.846). However, no statistically significant correlation was observed between dietary diversity and the presence of only hearing impairment (OR = 0.924, 95% CI, 0.815—1.047) (P < 0.05).

Conclusions and implications

The synthesis of research findings suggests that following diverse dietary patterns and healthy nutritional practices may be an effective and affordable way to prevent age-related decline in visual impairment and dual sensory impairment.
Fermented foods and probiotic consumption frequency as protective indicators for peri-implant diseases – a cross-sectional study
Authors: Sahin Tugba
Published: July 2024

Background

Due to their modulatory effect on biofilm growth, bacterial gene expressions, and host-modulation effects, fermented foods and probiotic products could potentially have a protective role against peri-implant diseases. This cross-sectional study aimed to examine the association of consumption of fermented foods and products containing probiotics, with peri-implant health and diseases.

Methods

A total of 126 implants were included. The peri-implant health status (peri-implantitis, peri-implant mucositis, and peri-implant health) was assessed through Chicago’s Classification of periodontal and peri-implant Diseases and Conditions. A questionnaire was used to evaluate the consumption patterns of fermented and probiotic foods and product. One-way ANOVA was employed to compare the 3 peri-implant conditions categories in terms of fermented food and probiotic consumption.

Results

There were significant differences in the daily and general consumption of yogurt, probiotic yogurt, kefir, ayran, vinegar, pomegranate syrup, whole meal bread, and homemade butter among peri-implantitis, peri-implant mucositis and peri-implant health (p < 0.05). The peri-implant health group consumed significantly more yogurt, kefir, ayran, vinegar, whole wheat bread, and homemade butter than peri-implant mucositis and peri-implantitis.

Conclusion

A higher consumption of fermented and probiotic foods may be associated with peri-implant health. Fermented and probiotic products may be useful for prevention of peri-implant diseases in patients with implants.
Network pharmacology and experimental validation to explore the role and potential mechanism of Liuwei Dihuang Decoction in prostate cancer
Authors: Zhan Xiangyang , Li Haoze , Jin Jingyun , Ju Xiran , Gao Jiawei , Chen Xinglin , Yuan Fuwen , Gu Jianyi , Xu DongLiang , Ju Guanqun
Published: July 2024

Objective

To evaluate the anti-tumor effector of Liuwei Dihuang Decoction (LWDHD) in prostate cancer (PCa) and explore the potential mechanism using experimental validation, network pharmacology, bioinformatics analysis, and molecular docking.

Methods

CCK test, Clone formation assay and wound-healing assays were used to determine the effect of LWDHD on prostate cancer growth and metastasis. The active ingredients and targets of LWDHD were obtained from the TCMSP database, and the relevant targets were selected by GeneCards, OMIM and DisGeNET databases for PCa. The cross-targets of drugs and disease were imported into the STRING database to construct protein interactions. The network was also visualized using Cytoscape software and core targets are screened using the Network Analyzer plug-in. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were analyzed using R software. TCGA database was used to analyze the correlation of bioinformatics genes. AutoDock vina was used to predict the molecular docking and binding ability of active ingredients to key targets. Through WB and q-PCR experiments, the above gene targets were detected to verify the effect of LWDHD on PCa.

Results

CCK and scratch tests confirmed that LWDHD could inhibit the proliferation, invasion and migration of prostate cancer cells. Clone formation experiments showed that LWDHD inhibited the long-term proliferative capacity of PC3 cells. LWDHD and PCa had a total of 99 common targets, establishing a “drug-ingredient-common target” network. Through GO and KEGG enrichment analysis, PI3K/AKT, MAPK, TP53 pathway, MYC, TNF pathway and other signaling pathways were found. Bioinformatics analysis showed that MYC gene was highly expressed and CCND1 and MAPK1 were low expressed in prostate cancer tissues. In addition, TP53, AKT1, MYC, TNF and CCND1 were positively correlated with MAPK1, among which AKT1 and CCND1 were most closely correlated with MAPK1. Molecular docking results showed that quercetin, kaempferol, β-sitosterol and other main active ingredients of LWDHD treatment for PCa were combined with core proteins MAPK1 and AKT1 well. WB and q-PCR results showed that LWDHD inhibited the expression of PI3K and AKT in PC3 cells.

Conclusion

The mechanism of LWDHD therapy for PCa is a multi-target and multi-pathway complex process, which may be related to the biological processes mediated by MAPK1 and AKT1 pathways, such as cell proliferation and inhibition of metastasis, and the regulation of signaling pathways. The PI3K/AKT signaling pathway may be a central pathway of LWDHD to inhibit prostate cancer proliferation.
Motivation to work and attitudes towards retirement among physicians
Authors: Jung Franziska U. , Bodendieck Erik , Luppa Melanie , Riedel-Heller Steffi G.
Published: July 2024

Background

The healthcare system is currently in a state of tension due to a shortage of physicians, the early retirement of health care professionals and an increasing need for care within an (aging) society. Therefore, the aim of the present study was to examine physicians’ attitudes towards retirement and possible influencing factors on their motivation to work.

Method

Data were collected as part of a baseline survey of a long-term study. The sample includes a variety of physicians (n = 625), working in outpatient or inpatient care, who have not yet reached the retirement age of 67. The primary outcome was to survey attitudes towards retirement using the Motivation to Work scale. Work-related characteristics (e.g., with regard to contract or working hour) as well as job satisfaction, overall health, and burnout were also included in the analyses (correlations and linear regression models).

Results

According to the results, sociodemographic characteristics are not significantly related to motivation to work, whereas the other parameters (satisfaction, health, and burnout) influence attitudes towards retirement significantly.

Conclusions

The results underline the need to improve the occupational conditions of physicians across different medical settings. More research is needed to understand physicians‘ decision-making with regard to retirement, especially in terms of work-related characteristics and differences.
Pharmacists’ attitudes towards interprofessional collaboration to optimise medication use in older patients in Switzerland: a survey study
Authors: Lüthold Renata Vidonscky , Cateau Damien , Jenkinson Stephen Philip , Streit Sven , Jungo Katharina Tabea
Published: July 2024

Background

Collaboration between physicians and pharmacists facilitates the conduct of medication optimisation efforts. In the context of deprescribing, pharmacists’ roles are often described as making deprescribing recommendations to physicians. Little is known about factors associated with pharmacists’ willingness to make deprescribing recommendations and their interprofessional collaboration with physicians in Swiss primary care settings.

Objective

To explore pharmacists' perspectives on medication optimisation and deprescribing in older adults, and their preferences for interprofessional collaboration in Swiss primary care settings.

Methods

In this cross-sectional study, a random sample of 1000 pharmacist members of the Swiss Pharmacists Association pharmaSuisse was invited to participate in a survey on medication optimisation, deprescribing, and interprofessional collaboration. The survey contained three case vignettes of multimorbid patients with polypharmacy aged ≥ 80 years old, with different levels of dependency in activities in daily living (ADL) and cardiovascular disease (CVD). For each case vignette, pharmacists were asked if and which medications they would deprescribe. We calculated proportions of pharmacists’ willingness to deprescribe by case vignette and performed a multilevel logistic regression to assess associations between CVD, ADL, and willingness to deprescribe.

Results

One hundred thirty-eight (14%) pharmacists responded to the survey: 113 (82%) were female, their mean age was 44 years (SD = 11), and 66% (n = 77) reported having never received any specific training on how to conduct structured medication reviews. Eighty-three (72%) pharmacists reported to be confident in identifying deprescribing opportunities. All pharmacists were willing to deprescribe ≥ 1 medication in all vignettes. Patients with CVD were at lower odds of having medications deprescribed (OR = 0.27, 95%CI 0.21 to 0.36). Willingness to deprescribe was lower with higher dependency in ADL (medium versus low dependency: OR = 0.68, 95%CI 0.54 to 0.87, high versus low dependency: OR = 0.72, 95%CI 0.56 to 0.91). However, the effect of dependency in ADL on willingness to deprescribe was significantly modified by the history of CVD. One hundred five pharmacists (97%) reported to interact with physicians to clarify questions regarding prescriptions at least once a week and 88 (81%) wished to be more involved in deprescribing and medication review.

Conclusion

Pharmacists were willing to make deprescribing suggestions for older patients with polypharmacy, but two-thirds reported having received no formal training on how to perform structured medication reviews. Pharmacists would like to be more involved in the process of medication review and deprescribing, which should be leveraged in the context of Swiss primary care settings.
Associations of phosphorus concentrations with medial arterial calcification in lower-extremity arteries and diabetic foot in people with diabetes: a retrospective cross-sectional study
Authors: Li Peishan , Li Qingxian , Tang Mingyu , Hu Xingyun , Tian Jing , Zhang Jianbin , Yang Chuan , Zhu Baile
Published: July 2024

Background

The aim of this study was to investigate the associations of blood phosphorus levels with the risk of developing medial arterial calcification (MAC) in lower-limb arteries and diabetic foot (DF) in diabetes patients. We sought to enhance the understanding of the pathophysiology of diabetic complications and develop strategies to mitigate diabetes-related risks.

Methods

We conducted a retrospective analysis of 701 diabetic patients from the Department of Endocrinology at Sun Yat-Sen Memorial Hospital (2019–2023). We utilized multimodel-adjusted logistic regression to investigate the associations of serum phosphorus levels and the risk of developing MAC and DF. Restricted cubic spline plots were employed to model the relationships, and threshold analysis was used to identify inflection points. Subgroup analyses were performed to explore variations across different demographics. The diagnostic utility of phosphorus concentrations was assessed via the C index, net reclassification improvement (NRI), and integrated discrimination improvement (IDI).

Results

Of the 701 patients (mean age 63.9 years; 401 (57.20%) were male), 333 (47.50%) had MAC, and 329 (46.93%) had DF. After controlling for numerous confounding variables, each one-unit increase in phosphorus concentrations was associated with an increased risk of developing MAC (OR 2.65, 95% CI 1.97–3.57, p < 0.001) and DF (OR 1.54, 95% CI 1.09–2.18, p = 0.014). Phosphorus levels demonstrated a linear risk association, with risk not being uniform on either side of the inflection point, which was approximately 3.28 mg/dL for MAC and varied for DF (3.26 to 3.81 mg/dL). Adding the phosphorus as an independent component to the diagnostic model for MAC and DF increased the C index, NRI, and IDI to varying degrees.

Conclusions

Elevated serum phosphorus levels are significantly associated with an increased risk of developing MAC and DF among diabetic people. These findings suggest that phosphorus management could be integrated into routine diagnostic processes to improve the identification and management of lower-extremity diabetic complications.

Graphical abstract
Enzyme/ROS dual-sensitive nanoplatform with on-demand Celastrol release capacity for enhanced ulcerative colitis therapy by ROS scavenging, microbiota rebalancing, inflammation alleviating
Authors: Shi Jinfeng , Zhou Jiahui , Liu Bo , Lin Kezhou , Xie Xingliang , Han Xue , Sheng Yanmei , Liu Yihan , He Congjian , Zhou Yujin , Zhu Nan , Yang Qian , Luo Ruifeng , Li Yi
Published: July 2024

Background

The oral administration of drugs for treating ulcerative colitis (UC) is hindered by several factors, including inadequate gastrointestinal stability, insufficient accumulation in colonic lesions, and uncontrolled drug release.

Methods

A multiple sensitive nano-delivery system comprising β-cyclodextrin (CD) and 4-(hydroxymethyl)phenylboronic acid (PAPE) with enzyme/reactive oxygen species (ROS) sensitivity was developed to load celastrol (Cel) as a comprehensive treatment for UC.

Results

Owing to the positive charge in the site of inflamed colonic mucosa, the negatively charged nanomedicine (Cel/NPs) could efficiently accumulate. Expectedly, Cel/NPs showed excellent localization ability to colon in vitro and in vivo tests. The elevated concentration of ROS and intestinal enzymes in the colon microenvironment quickly break the CD, resulting in Cel release partially to rebalance microbiota and recover the intestinal barrier. The accompanying cellular internalization of residual Cel/NPs, along with the high concentration of cellular ROS to trigger Cel burst release, could decrease the expression of inflammatory cytokines, inhibit colonic cell apoptosis, promote the macrophage polarization, scavenge ROS, and regulate the TLR4/NF-κB signaling pathway, which certified that Cel/NPs possessed a notably anti-UC therapy outcome.

Conclusions

We provide a promising strategy for addressing UC symptoms via an enzyme/ROS-sensitive oral platform capable of releasing drugs on demand.

Graphical Abstract
Signaling dynamics in coexisting monoclonal cell subpopulations unveil mechanisms of resistance to anti-cancer compounds
Authors: Blanchard Claire E. , Gomeiz Alison T. , Avery Kyle , Gazzah Emna El , Alsubaie Abduljalil M. , Sikaroodi Masoumeh , Chiari Ylenia , Ward Chelsea , Sanchez Jonathan , Espina Virginia , Petricoin Emanuel , Baldelli Elisa , Pierobon Mariaelena
Published: July 2024

Background

Tumor heterogeneity is a main contributor of resistance to anti-cancer targeted agents though it has proven difficult to study. Unfortunately, model systems to functionally characterize and mechanistically study dynamic responses to treatment across coexisting subpopulations of cancer cells remain a missing need in oncology.

Methods

Using single cell cloning and expansion techniques, we established monoclonal cell subpopulations (MCPs) from a commercially available epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer cell line. We then used this model sensitivity to the EGFR inhibitor osimertinib across coexisting cell populations within the same tumor. Pathway-centered signaling dynamics associated with response to treatment and morphological characteristics of the MCPs were assessed using Reverse Phase Protein Microarray. Signaling nodes differentially activated in MCPs less sensitive to treatment were then pharmacologically inhibited to identify target signaling proteins putatively implicated in promoting drug resistance.

Results

MCPs demonstrated highly heterogeneous sensitivities to osimertinib. Cell viability after treatment increased > 20% compared to the parental line in selected MCPs, whereas viability decreased by 75% in other MCPs. Reduced treatment response was detected in MCPs with higher proliferation rates, EGFR L858R expression, activation of EGFR binding partners and downstream signaling molecules, and expression of epithelial-to-mesenchymal transition markers. Levels of activation of EGFR binding partners and MCPs’ proliferation rates were also associated with response to c-MET and IGFR inhibitors.

Conclusions

MCPs represent a suitable model system to characterize heterogeneous biomolecular behaviors in preclinical studies and identify and functionally test biological mechanisms associated with resistance to targeted therapeutics.
GRASLND regulates melanoma cell progression by targeting the miR-218-5p/STAM2 axis
Authors: Ma Aiwei , Shi Wenqi , Chen Liyun , Huang Zijian , Zhang Yiwen , Tang Zixuan , Jiang Wenshi , Xu Mengjing , Zhou Jianda , Zhang Wancong , Tang Shijie
Published: July 2024

Background

Increasing evidence suggests that long noncoding RNAs (lncRNAs) play important regulatory roles in biological processes and are dysregulated in numerous tumors. The lncRNA GRASLND functions as an oncogene in many cancers, but its role in skin cutaneous melanoma (SKCM) requires further investigation.

Methods

SiRNA transfection, wound − healing and transwell assays were performed to evaluate the effect of GRASLND on cellular function.

Results

The present study demonstrated that GRASLND expression is increased in SKCM tissues and cell lines. The high expression of GRASLND was correlated with poor prognosis and immunotherapy outcomes. Knockdown of GRASLND significantly inhibited cell migration and invasion. In addition, we found that miR-218-5p directly binds to its binding site on GRASLND, and GRASLND and miR-218-5p demonstrate mutual inhibition. Furthermore, the miR-218-5p inhibitor partially eliminated the knockdown of GRASLND and inhibited its expression. We also demonstrated that GRASLND acts as a miR-218-5p sponge that positively regulates STAM2 expression in SKCM cells.

Conclusion

In summary, these data suggest that GRASLND functions by regulating miR-218-5p/STAM2 expression, suggesting an important role for the lncRNA‒miRNA–mRNA functional network and a new potential therapeutic target for SKCM.
Analysis of risky sexual behaviors among male college students who were sexually active in Sichuan, China: a cross-sectional survey
Authors: Dai Yingxue , Li Yajie , Zhou Dinglun , Zhang Jianxin
Published: July 2024

Background

Males have accounted for a significant share of new HIV infections among young people in the recent years. This study aimed to identify the factors associated with risky sexual behaviors, including early sexual debut, multiple sexual partnership and condomless sex, among sexually active male college students and provide implications for tailored health interventions.

Methods

The cross-sectional study was conducted from December 2020 to December 2021 in 16 colleges that were located in Sichuan Province, one of the high-risk areas in China. Overall 1640 male college students who reported sexually experienced were analyzed in this study. Multivariable logistic regression analysis was applied to determine factors associated with early sexual debut, multiple sexual partnership and condomless sex.

Results

The average age of included male students was 19.95 ± 1.56. Of them, 27.74% initiated sexual behavior early, 48.60% reported multiple sexual partnership, and 16.52% did not use condoms at the latest sexual intercourse. Students who were younger (age ≤ 19, AOR = 7.60, 95%CI: 4.84–11.93; age20-21, AOR = 3.26, 95%CI: 2.04–5.21) and self-identified as sexual minorities (AOR = 2.38, 95%CI: 1.69–3.36) were more likely to have early sexual debut. The odds of having multiple sexual partners were higher among those who were ethnic minorities (AOR = 1.79, 95%CI: 1.33–2.41) and accepted extramarital sex (AOR = 1.33, 95%CI: 1.03–1.71). The likelihood of engaging in condomless sex at the latest sexual intercourse was lower among those who had sufficient knowledgeable about HIV (AOR = 0.63, 95%CI: 0.44–0.89), were very confident in condom use efficacy (AOR = 0.26, 95%CI: 0.16–0.43) and confident (AOR = 0.48, 95%CI: 0.34–0.69). Early sexual debut was positively associated with multiple sexual partnership (AOR = 3.64, 95%CI: 2.82–4.71) and condomless sex at the latest intercourse (AOR = 1.53, 95%CI: 1.07–2.20), respectively.

Conclusion

Early sexual debut, multiple sexual partnership and condomless sex were of considerable concern among male college students. Comprehensive sex education curricula were advised by developing customized information on HIV prevention, sexuality and empowering students with assertiveness and negotiation skills with regard to condom use during and before college.
Evaluating the effect of injection protocols on intrathecal solute dispersion in non-human primates: an in vitro study using a cynomolgus cerebrospinal fluid system
Authors: Burla Goutham Kumar Reddy , Shrestha Dev , Bowen Mayumi , Horvath Joshua D. , Martin Bryn A.
Published: July 2024

Background

Achieving effective drug delivery to the central nervous system (CNS) remains a challenge for treating neurological disorders. Intrathecal (IT) delivery, which involves direct injection into the cerebrospinal fluid (CSF), presents a promising strategy. Large animal studies are important to assess the safety and efficacy of most drugs and treatments and translate the data to humans. An understanding of the influence of IT injection parameters on solute distribution within the CNS is essential to optimize preclinical research, which would potentially help design human clinical studies.

Methods

A three-dimensional (3D) in vitro model of a cynomolgus monkey, based on MRI data, was developed to evaluate the impact of lumbar injection parameters on intrathecal solute dispersion. The parameters evaluated were (a) injection location, (b) bolus volume, (c) flush volume, (d) bolus rate, and (e) flush rate. To simulate the CSF flow within the subarachnoid space (SAS), an idealized CSF flow waveform with both cardiac and respiratory-induced components was input into the model. A solution of fluorescein drug surrogate tracer was administered in the lumbar region of the 3D in vitro model filled with deionized water. After injection of the tracer, the CSF system wide-solute dispersion was imaged using high-resolution cameras every thirty seconds for a duration of three hours. To ensure repeatability each injection protocol was repeated three times. For each protocol, the average spatial–temporal distribution over three hours post-injection, the area under the curve (AUC), and the percent injected dose (%ID) to extra-axial CSF (eaCSF) at three hours were determined.

Results

The changes to the lumbar injection parameters led to variations in solute distribution along the neuro-axis. Specifically, injection location showed the most impact, enhancing the delivery to the eaCSF up to + 10.5%ID (p = 0.0282) at three hours post-injection. Adding a post-injection flush of 1.5 ml at 1 ml/min increased the solute delivery to the eaCSF by + 6.5%ID (p = 0.0218), while the larger bolus volume resulted in a + 2.3%ID (p = 0.1910) increase. The bolus and flush rates analyzed had minimal, statistically non-significant effects.

Conclusion

These results predict the effects of lumbar injection parameters on solute distribution in the intrathecal space in NHPs. Specifically, the choice of injection location, flush, and bolus volume significantly improved solute delivery to eaCSF. The in vitro NHP CSF model and results offer a system to help predict and optimize IT delivery protocols for pre-clinical NHP studies.
A retrospective analysis of transudative pleural effusion due to fibrosing mediastinitis
Authors: Yu Yan-Xia , An Li , Ma Zhan-Hong , Shi Huan-Zhong , Yang Yuan-Hua
Published: July 2024

Background

Pleural effusion caused by fibrosing mediastinitis is rarely reported. This study aimed to summarize the clinical manifestations, diagnosis and treatment of transudative pleural effusion due to fibrosing mediastinitis.

Methods

Medical records and follow-up data of 7 patients with transudative pleural effusion due to fibrosing mediastinitis in Beijing Chaoyang Hospital between May 2014 and Feb 2018 were retrospectively analyzed.

Results

These patients included 4 males and 3 females, with an average age of (64 ± 9) years. There were 3 left-sided effusions, 2 right-sided effusions and 2 bilateral effusions. Previous or latent tuberculosis was found in 6 patients. Pulmonary hypertension was indicated by echocardiography in all the 7 patients. Computed tomography pulmonary angiography (CTPA) of all the 7 cases showed increased soft tissue images visible in the mediastinum and bilateral hilus, different degrees of stenosis or occlusion in the pulmonary artery and pulmonary vein. In addition, 4 cases were found of right middle lobe atelectasis with a mediastinal window setting. There was interstitial pulmonary edema on the side of pleural effusion with a lung window setting. All the 7 patients were treated with intermittent drainage of pleural effusion combined with diuretic therapy. Five patients were treated with antituberculosis therapy. Up to now, two patients died of right heart failure and respiratory failure after 2 and 16 months respectively; The remaining 5 patients were still in follow up.

Conclusion

Fibrosing mediastinitis can lead to pulmonary vein stenosis or occlusion, and thus cause transudative pleural effusion, which can be detected by CTPA. Pulmonary hypertension, long time of cough, and a history of tuberculosis are common in these patients. The common therapy is intermittent drainage of pleural effusion combined with diuretic therapy.
Making sense of change after Intensive Trauma Treatment: a mixed-methods study into adolescents’ experience of efficacy
Authors: van Ee Elisa , de Beijer Dani , Florisson Desirée , Geuskens Fenna
Published: July 2024

Background

While evidence-based interventions are effective for children with post-traumatic stress disorder (PTSD), some adolescents may not respond sufficiently. Intensive trauma treatment (ITT) has shown promise for adults, but research on its efficacy for adolescents is limited. This study therefore aimed to explore the efficacy and subjective experience of change in adolescents participating in ITT.

Methods

The present study employed a mixed-methods approach among a sample of adolescents with PTSD (N = 22; 90.1% female, age M = 17.0, SD = 1.72) who participated in an ITT program. Clinical data and narratives were combined to assess treatment efficacy and subjective experiences of change.

Results

Quantitative analysis revealed a significant reduction in PTSD symptoms post-ITT, aligning with prior research. Qualitative analysis highlighted themes such as negative thoughts impacting treatment success, the importance of social support, and identity-related struggles.

Conclusions

The study contributes to understanding ITT efficacy and emphasizes the need for developmental sensitivity, systemic interventions, and continued research to enhance PTSD treatment for adolescents.
Participant-derived cell line transcriptomic analyses and mouse studies reveal a role for ZNF335 in plasma cholesterol statin response
Authors: Theusch Elizabeth , Ting Flora Y. , Qin Yuanyuan , Stevens Kristen , Naidoo Devesh , King Sarah M. , Yang Neil V. , Orr Joseph , Han Brenda Y. , Cyster Jason G. , Chen Yii-Der I. , Rotter Jerome I. , Krauss Ronald M. , Medina Marisa W.
Published: July 2024

Background

Statins lower circulating low-density lipoprotein cholesterol (LDLC) levels and reduce cardiovascular disease risk. Though highly efficacious in general, there is considerable inter-individual variation in statin efficacy that remains largely unexplained.

Methods

To identify novel genes that may modulate statin-induced LDLC lowering, we used RNA-sequencing data from 426 control- and 2 µM simvastatin-treated lymphoblastoid cell lines (LCLs) derived from European and African American ancestry participants of the Cholesterol and Pharmacogenetics (CAP) 40 mg/day 6-week simvastatin clinical trial (ClinicalTrials.gov Identifier: NCT00451828). We correlated statin-induced changes in LCL gene expression with plasma LDLC statin response in the corresponding CAP participants. For the most correlated gene identified (ZNF335), we followed up in vivo by comparing plasma cholesterol levels, lipoprotein profiles, and lipid statin response between wild-type mice and carriers of a hypomorphic (partial loss of function) missense mutation in Zfp335 (the mouse homolog of ZNF335).

Results

The statin-induced expression changes of 147 human LCL genes were significantly correlated to the plasma LDLC statin responses of the corresponding CAP participants in vivo (FDR = 5%). The two genes with the strongest correlations were zinc finger protein 335 (ZNF335 aka NIF-1, rho = 0.237, FDR-adj p = 0.0085) and CCR4-NOT transcription complex subunit 3 (CNOT3, rho = 0.233, FDR-adj p = 0.0085). Chow-fed mice carrying a hypomorphic missense (R1092W; aka bloto) mutation in Zfp335 had significantly lower non-HDL cholesterol levels than wild-type C57BL/6J mice in a sex combined model (p = 0.04). Furthermore, male (but not female) mice carrying the Zfp335R1092W allele had significantly lower total and HDL cholesterol levels than wild-type mice. In a separate experiment, wild-type mice fed a control diet for 4 weeks and a matched simvastatin diet for an additional 4 weeks had significant statin-induced reductions in non-HDLC (−43 ± 18% and −23 ± 19% for males and females, respectively). Wild-type male (but not female) mice experienced significant reductions in plasma LDL particle concentrations, while male mice carrying Zfp335R1092W allele(s) exhibited a significantly blunted LDL statin response.

Conclusions

Our in vitro and in vivo studies identified ZNF335 as a novel modulator of plasma cholesterol levels and statin response, suggesting that variation in ZNF335 activity could contribute to inter-individual differences in statin clinical efficacy.