bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma proteomic characterization of colorectal cancer patients with FOLFOX chemotherapy by integrated proteomics technology
Authors: Wang Xi , Zhang Keren , He Wan , Zhang Luobin , Gao Biwei , Tian Ruijun , Xu Ruilian
Published: April 2024

Background

Colorectal Cancer (CRC) is a prevalent form of cancer, and the effectiveness of the main postoperative chemotherapy treatment, FOLFOX, varies among patients. In this study, we aimed to identify potential biomarkers for predicting the prognosis of CRC patients treated with FOLFOX through plasma proteomic characterization.

Methods

Using a fully integrated sample preparation technology SISPROT-based proteomics workflow, we achieved deep proteome coverage and trained a machine learning model from a discovery cohort of 90 CRC patients to differentiate FOLFOX-sensitive and FOLFOX-resistant patients. The model was then validated by targeted proteomics on an independent test cohort of 26 patients.

Results

We achieved deep proteome coverage of 831 protein groups in total and 536 protein groups in average for non-depleted plasma from CRC patients by using a Orbitrap Exploris 240 with moderate sensitivity. Our results revealed distinct molecular changes in FOLFOX-sensitive and FOLFOX-resistant patients. We confidently identified known prognostic biomarkers for colorectal cancer, such as S100A4, LGALS1, and FABP5. The classifier based on the biomarker panel demonstrated a promised AUC value of 0.908 with 93% accuracy. Additionally, we established a protein panel to predict FOLFOX effectiveness, and several proteins within the panel were validated using targeted proteomic methods.

Conclusions

Our study sheds light on the pathways affected in CRC patients treated with FOLFOX chemotherapy and identifies potential biomarkers that could be valuable for prognosis prediction. Our findings showed the potential of mass spectrometry-based proteomics and machine learning as an unbiased and systematic approach for discovering biomarkers in CRC.
Yak genome database: a multi-omics analysis platform
Authors: Jiang Hui , Chai Zhi-Xin , Chen Xiao-Ying , Zhang Cheng-Fu , Zhu Yong , Ji Qiu-Mei , Xin Jin-Wei
Published: April 2024

Background

The yak (Bos grunniens) is a large ruminant species that lives in high-altitude regions and exhibits excellent adaptation to the plateau environments. To further understand the genetic characteristics and adaptive mechanisms of yak, we have developed a multi-omics database of yak including genome, transcriptome, proteome, and DNA methylation data.

Description

The Yak Genome Database (http://yakgenomics.com/) integrates the research results of genome, transcriptome, proteome, and DNA methylation, and provides an integrated platform for researchers to share and exchange omics data. The database contains 26,518 genes, 62 transcriptomes, 144,309 proteome spectra, and 22,478 methylation sites of yak. The genome module provides access to yak genome sequences, gene annotations and variant information. The transcriptome module offers transcriptome data from various tissues of yak and cattle strains at different developmental stages. The proteome module presents protein profiles from diverse yak organs. Additionally, the DNA methylation module shows the DNA methylation information at each base of the whole genome. Functions of data downloading and browsing, functional gene exploration, and experimental practice were available for the database.

Conclusion

This comprehensive database provides a valuable resource for further investigations on development, molecular mechanisms underlying high-altitude adaptation, and molecular breeding of yak.
Incidence and factors associated with failed spinal anaesthesia among patients undergoing surgery: a multi- center prospective observational study
Authors: Demilie Atalay Eshetie , Denu Zewditu Abdissa , Bizuneh Yosef Belay , Gebremedhn Endale Gebreegziabher
Published: April 2024

Background

Failed spinal anaesthesia causes prolonging of operation time, insufficient analgesia for surgery and needs repeating spinal anaesthesia which in turn causes local anaesthesia toxicity, high spinal and total spinal, and conversion to general anaesthesia. However, the problem remains unexplored in Amhara regional state comprehensive specialized hospitals.

Objective

To determine incidence and factors associated with failed spinal anaesthesia among patients undergoing surgery in selected Amhara National Regional State comprehensive specialized hospitals, Northwest Ethiopia, 2023.

Methods

Multi-center prospective observational study was conducted. Data was collected using questionnaire and checklist. All consecutive scheduled emergency and elective patients were included in the study. Data was transformed from Epi data to SPSS and logistic regression analysis was done. Both crude and adjusted odds ratio were used to assess the strength of association. Variables with a p-value of less than 0.05 were considered as statistically significant.

Results

A total of 532 patients were included in this study with a response rate of 98%. Incidence of failed spinal anaesthesia was 22.4% (CI = 19-25.9). Emergency surgery (AOR = 7.01, CI = 4.5–12.7), dose of bupivacaine of ≤ 10 mg (AOR = 3.02, CI = 1.3–10.2), work experience of anaesthetist < 2 years (AOR = 3.1, CI = 1.7–5.72), bloody CSF (AOR = 8.5, CI = 2.53–18.5), hyperbaric local anaesthetic drug (AOR = 3.3, 95% CI = 3.2–8.2) and local anaesthetist without adjuvants (AOR = 5.25, CI = 2.62–14.2) were associated failed spinal anaesthesia.

Conclusion and recommendation

The incidence of failed spinal anaesthesia was high in Amhara Region comprehensive specialized hospitals. We suggest that anaesthesia providers should minimize failure by using adjuvants and appropriate dose of local anaesthetic. Additionally, simulation training should be given for anaesthesia trainees to improve their skills and to produce competent professionals.
Serum albumin and cardiovascular disease: a Mendelian randomization study
Authors: Huang Taoke , An Zhifeng , Huang Ziru , Gao Weiyang , Hao Benchuan , Xu Juan
Published: April 2024

Background

An increasing body of evidence suggests that serum albumin levels play a role in cardiovascular diseases. However, the specific causal relationship between serum albumin levels and cardiovascular disease remains partially unknown.

Methods

Mendelian randomization (MR) was employed in this study to examine potential causal relationships between instrumental variables and cardiovascular diseases. Specifically, we utilized genetic variants of serum albumin levels within the reference range as our instrumental variables. To acquire data on genetic associations with cardiovascular diseases, we sourced information from renowned genome-wide association studies such as UK BioBank, EMBL-EBI, and FinnGen. Notably, our study leveraged summary statistics from large cohorts that have been previously described.

Results

We explored the association between serum albumin levels and various conditions, including heart failure (HF), venous thromboembolism (VTE), stroke, atrial fibrillation (AF), coronary artery disease (CAD), type 2 diabetes (T2DM), and pulmonary heart disease (PHD). Genetically predicted serum albumin levels were associated with PHD (odds ratio = 0.737, 95% CI = 0.622 − 0.874, P < 0.001), AF (odds ratio = 0.922, 95% CI = 0.870 − 0.977, P = 0.006), VTE (odds ratio = 0.993, 95% CI = 0.991 − 0.995, P < 0.001), and Stroke (odds ratio = 0.997, 95% CI = 0.995 − 0.999, P = 0.002). However, genetically predicted serum albumin level traits were not associated with HF, CAD and T2DM.

Conclusion

Our study demonstrates a significant association between serum albumin levels and cardiovascular disease, underscoring the crucial role of low serum albumin as a predictive factor in patients with cardiovascular disease.
Comparison of the effect of phenobarbital & levetiracetam in the treatment of neonatal abstinence syndrome (NAS) as adjuvant treatment in neonates admitted to the neonatal intensive care unit: a randomized clinical trial
Authors: Jamali Zahra , Molaei-Farsangi Mohammad Hosein , Ahmadipour Habibeh , Bahmanbijari Bahareh , Sabzevari Fatemeh , Parizi Zahra Daei
Published: April 2024

Background

Infants who are born from mothers with substance use disorder might suffer from neonatal abstinence syndrome (NAS) and need treatment with medicines. One of these medicines is phenobarbital, which may cause side effects in long-term consumption. Alternative drugs can be used to reduce these side effects. This study seeks the comparison of the effects of phenobarbital & levetiracetam as adjuvant therapy in neonatal abstinence syndrome.

Methods

This randomized clinical trial was performed in one year from May 2021 until May 2022. The neonates who were born from mothers with substance use disorder and had neonatal abstinence syndrome in Afzalipoor Hospital of Kerman were studied. The treatment started with morphine initially and every four hours the infants were checked. The infants who were diagnosed with uncontrolled symptoms After obtaining informed consent from the parents were randomly divided into two groups and treated with secondary drugs, either phenobarbital or levetiracetam.

Results

Based on the obtained results, it was clear that there was no significant difference between the hospitalization time of the two infant groups under therapy (phenobarbital: 18.59 days versus Levetiracetam 18.24 days) (P-value = 0.512). Also, there was no significant difference between both groups in terms of the frequency of re-hospitalization during the first week after discharge, the occurrence of complications, and third treatment line prescription (P-value = 0.644).

Conclusions

Based on the obtained results, like hospitalization duration time (P-value = 0.512) it seems that levetiracetam can be used to substitute phenobarbital in treating neonatal abstinence syndrome.

Trial registration

The current study has been registered in the Iran registry of clinical trials website (fa.irct.ir) on the date 25/2/2022 with registration no. IRCT20211218053444N2.
Growth and endocrinopathies among children with β-Thalassemia major treated at Dubai Thalassemia centre
Authors: Almahmoud Rabah , Hussein Amal , Khaja Fatheya Al , Soliman Ahmed Farrag , Dewedar Hany , Shareef Zainab Al , Mathai Sarah
Published: April 2024

Background

β-Thalassemia major (BTM) is one of the most common hereditary anemias worldwide. Patients suffer from iron overload that results from repeated blood transfusion This in turn leads to multiple organ damage and endocrinopathies. This study aims to assess the prevalence of growth retardation, hypothyroidism, and diabetes mellitus in children and adolescents with BTM treated at Dubai Thalassemia Centre.

Methods

A total of 105 children and adolescents were included in this retrospective observational study.

Results

39 children and 66 adolescents’ data were analyzed. Females composed 51.3% (n = 20) of children and 53.0% (n = 35) of adolescents. Pretransfusion hemoglobin below 9 gm/dl was observed in 10.8% (n = 4) and 10.6% (n = 7) in children and adolescents, respectively. The mean age of menarche was 13.5 years. Among all study participants, 22.6% (n = 14) had normal height velocity whereas 37.1% (n = 23) had reduced height velocity in one year and 40.3% (n = 25) had reduced height velocity in two consecutive years. The proportion of children and adolescents showing reduced height velocity was significantly higher in females compared to the males (90.6% versus 63.3%, respectively, Chi-square = 6.597, p-value = 0.010). Although none of the study participants had diabetes mellitus, 26.1% (n = 12/46) had pre-diabetes. Elevated TSH was observed in 14.7% (n = 5) children and 8.1% (n = 5) adolescents while low FT4 was reported in one child and one adolescent.

Conclusion

Of all endocrinopathies seen among children and adolescents with BTM, growth delay remains the main concern for this group of patients. Effective treatment is key to further reducing endocrinopathies. Although the sample size is limited, we postulate that the low percentage of endocrinopathies among children with BTM treated at Dubai thalassemia center and the low level of pretransfusion anemia reflect the effective transfusion and chelation at the center.
Sex differences in prevalence and clinical correlates of internet addiction among Chinese adolescents with schizophrenia
Authors: Zhong Yunhui , Lai Shuixiu , Hu Anquan , Liao Yuanping , Li Yibo , Zhang Zheng , Zhang Xiang-Yang
Published: April 2024

Background

Patients with schizophrenia (SCZ) exhibit sex differences in various aspects, and patients with SCZ have a high prevalence of internet addiction (IA). However, sex differences in IA among patients with SCZ mostly remain unstudied, particularly in Chinese adolescent patients with SCZ. This study investigated sex differences in prevalence, risk factors, and clinical correlates of IA among Chinese adolescent patients with SCZ.

Methods

A total of 706 adolescent patients with SCZ were enrolled in this study using a cross-sectional design and a convenience sampling method. Demographics and clinical data of the patients were collected using a standardized clinical assessment form. The Positive and Negative Syndrome Scale (PANSS) and the Young’s Internet Addiction Test were used to evaluate psychopathological symptoms and IA respectively.

Results

Overall, the prevalence of IA among Chinese adolescent patients with SCZ was 26.30% (95% CI: 23.09-29.60%). In Chinese adolescents with SCZ, there was a sex difference in the comorbidity of IA (males: 33.33% vs. females: 21.69%). Binary logistic regression analysis showed that IA was significantly predicted by good socioeconomic status in male and female patients with SCZ. City of living and PANSS total score were associated with IA in male patients with SCZ. In contrast, hospitalization rate and depression score were associated with IA in female patients with SCZ.

Conclusion

Our study suggests sex differences in clinical correlates of IA in Chinese adolescent patients with SCZ. An additional longitudinal study is required to confirm the findings of the present study.
Exploring differences in the utilization of the emergency department between migrant and non-migrant populations: a systematic review
Authors: Acquadro-Pacera Giulia , Valente Martina , Facci Giulia , Molla Kiros Bereket , Della Corte Francesco , Barone-Adesi Francesco , Ragazzoni Luca , Trentin Monica
Published: April 2024

Background

Migrants face several barriers when accessing care and tend to rely on emergency services to a greater extent than primary care. Comparing emergency department (ED) utilization by migrants and non-migrants can unveil inequalities affecting the migrant population and pave the way for public health strategies aimed at improving health outcomes. This systematic review aims to investigate differences in ED utilization between migrant and non-migrant populations to ultimately advance research on migrants’ access to care and inform health policies addressing health inequalities.

Methods

A systematic literature search was conducted in March 2023 on the Pubmed, Scopus, and Web of Science databases. The included studies were limited to those relying on data collected from 2012 and written in English or Italian. Data extracted included information on the migrant population and the ED visit, the differences in ED utilization between migrants and non-migrants, and the challenges faced by migrants prior to, during, and after the ED visit. The findings of this systematic review are reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines.

Results

After full-text review, 23 articles met the inclusion criteria. All but one adopted a quantitative methodology. Some studies reported a higher frequency of ED visits among migrants, while others a higher frequency among non-migrants. Migrants tend to leave the hospital against medical advice more frequently than the native population and present at the ED without consulting a general practitioner (GP). They are also less likely to access the ED via ambulance. Admissions for ambulatory care-sensitive conditions, namely health conditions for which adequate, timely, and effective outpatient care can prevent hospitalization, were higher for migrants, while still being significant for the non-migrant population.

Conclusions

The comparison between migrants’ and non-migrants’ utilization of the ED did not suggest a clear pattern. There is no consensus on whether migrants access EDs more or less than non-migrants and on whether migrants are hospitalized at a higher or lower extent. However, migrants tend to access EDs for less urgent conditions, lack a referral from a GP and access the ED as walk-ins more frequently. Migrants are also discharged against medical advice more often compared to non-migrants. Findings of this systematic review suggest that migrants’ access to care is hindered by language barriers, poor insurance coverage, lack of entitlement to a GP, and lack of knowledge of the local healthcare system.
Translation, cross-cultural adaptation, and validation of the 10-item spine functional index (SFI-10) in the Brazilians with musculoskeletal spine disorders
Authors: do Nascimento Freitas Devyd Weyder , Dibai-Filho Almir Vieira , Pontes-Silva André , Araujo Gabriel Gardhel Costa , de Oliveira Augusto Ribeiro , da Cunha Leal Plinio , Gabel Charles Philip , Fidelis-de-Paula-Gomes Cid André , Cabido Christian Emmanuel Torres
Published: April 2024

Purpose

To translate and cross-culturally adapt the Spine Functional Index (SFI) into Brazilian Portuguese (SFI-Br) in individuals with musculoskeletal spine disorders.

Methods

Participants (n=194) answered the Numerical Pain Rating Scale (NPRS), 36-item Short-Form Health Survey (SF-36), Roland-Morris Disability Questionnaire for General Pain (RMDQ-g), and SFI-25 incorporating the SFI-10. Structural validity, from confirmatory factor analysis (CFA), used comparative fit index (CFI), Tucker-Lewis index (TLI), root mean square error of approximation (RMSEA), and chi-square/degrees of freedom (DF). The best structure was considered from the lower values of the Akaike Information Criterion (AIC) and Bayesian Information Criterion (BIC). Construct and criterion validity used Spearman’s correlation coefficient (rho). Internal consistency used Cronbach’s alpha, reliability used intraclass correlation coefficient (ICC2,1), with ceiling and floor effects determined. Error used the standard error of the measurement (SEM) and minimal detectable change, 90% level (MDC90).

Results

Adequate fit indices demonstrated an unequivocal one-factor structure only for the SFI-10 (chi-square/DF <3.00, CFI and TLI >0.90, RMSEA <0.08). The SFI-10-Br correlation was high with the SFI-Br (rho=0.914, p<0.001), moderate for the RMDQ-g (rho=-0.78), SF-36 functional capacity domain (rho=0.718) and NPRS (rho=-0.526); and adequate for the remaining SF-36 domains (rho>0.30). Test-retest reliability (ICC2,1=0.826) and internal consistency (alpha=0.864) were high. No ceiling or floor effects were observed, and error was satisfactory (SEM=9.08%, MDC90=25.15%).

Conclusion

The SFI Brazilian version was successfully produced with the 10-item version showing an unequivocal one-factor structure, high construct and criterion validity, reliability, internal consistency, and satisfactory error. Further research on responsiveness is required.
Phantom study of a fully automatic radioactive seed placement robot for the treatment of skull base tumours
Authors: Fanhao Meng , Dongsheng Xie , Nenghao Jin , Yu Song , Huanyu Tian , Bo Qiao , Bofu Liang , Ning Zhang , Shimin Chang , Runtao Gao , Xingguang Duan , Haizhong Zhang
Published: April 2024

Background

Interstitial brachytherapy is a form of intensive local irradiation that facilitates the effective protection of surrounding structures and the preservation of organ functions, resulting in a favourable therapeutic response. As surgical robots can perform needle placement with a high level of accuracy, our team developed a fully automatic radioactive seed placement robot, and this study aimed to evaluate the accuracy and feasibility of fully automatic radioactive seed placement for the treatment of tumours in the skull base.

Methods

A fully automatic radioactive seed placement robot was established, and 4 phantoms of skull base tumours were built for experimental validation. All the phantoms were subjected to computed tomography (CT) scans. Then, the CT data were imported into the Remebot software to design the preoperative seed placement plan. After the phantoms were fixed in place, navigation registration of the Remebot was carried out, and the automatic seed placement device was controlled to complete the needle insertion and particle placement operations. After all of the seeds were implanted in the 4 phantoms, postoperative image scanning was performed, and the results were verified via image fusion.

Results

A total of 120 seeds were implanted in 4 phantoms. The average error of seed placement was (2.51 ± 1.44) mm.

Conclusion

This study presents an innovative, fully automated radioactive particle implantation system utilizing the Remebot device, which can successfully complete automated localization, needle insertion, and radioactive particle implantation procedures for skull base tumours. The phantom experiments showed the robotic system to be reliable, stable, efficient and safe. However, further research on the needle-soft tissue interaction and deformation mechanism of needle puncture is still needed.
Assessment of physical properties of bioactive glass-modified universal multimode adhesive and its bonding potential to artificially induced caries affected dentin
Authors: Kazem Nada E. , El-Refai Dina A. , Alian Ghada
Published: April 2024

Background

To evaluate the physical properties of bioactive glass-modified universal multimode adhesive and its micro-tensile bond strength (µTBS) to artificially induced caries-affected dentin.

Methods

All bond universal adhesive was used in the study. Specimens were divided into 2 main groups: control unmodified adhesive and 5 wt% BAG modified adhesive. The degree of conversion, pH, bioactivity, and viscosity of the adhesives were tested with n = 5 for each test. Micro-tensile bond strength evaluation was done in etch & rinse (ER) and selective-etch (SE) modes, where 24 human molar teeth were used (n = 3), 12 teeth for immediate bond strength, and the other 12 were tested after 6 months of storage in simulated body fluid (SBF).

Results

No significant difference was found between the control and the 5wt% BAG groups regarding the degree of conversion (61.01 ± 0.43 and 60.44 ± 0.61 respectively) and the viscosity (109.77 ± 22.3 and 124.3 ± 9.92 respectively). The control group revealed significantly lower pH values than the 5wt% BAG group (3.16 ± 0.5 and 4.26 ± 0.09 respectively). Immediate bond strength results revealed that the 5wt% BAG in the ER mode had the highest bond strength followed by the control group in the ER mode (44.16 ± 7.53 and 44.00 ± 7.96 respectively). SE groups showed that the immediate strength of the 5wt% BAG group was higher than the control group (42.09 ± 6.02 and 39.29 ± 6.64 respectively). After 6 months of storage, bond strength results revealed a decrease in bond strength values for the control groups but not for the 5wt% BAG in both application modes.

Conclusions

The incorporation of BAG (5wt%) improved the universal adhesive micro-tensile bond strength and bond durability for both adhesive application modes without affecting its degree of conversion or viscosity.
Challenges to conducting research on oral health with older adults living in long-term care facilities
Authors: Ramos Thayse Mayra Chaves , da Silva Alves Álvaro Augusto , Apolinário Thais Andrade , de Toledo Flávia Fonseca , Gomes Viviane Elisângela , Barbosa Kevan Guilherme Nóbrega , Sampaio Aline Araújo , Ferreira Raquel Conceição
Published: April 2024

Background

The challenges to conducting oral health studies involving older people in long-term care facilities (LTCFs) must be debated.

Objective

This study aimed to investigate researchers’ perceptions and experiences while conducting an epidemiological survey on oral health among older individuals residing in LTCFs.

Methods

A qualitative study was conducted involving six researchers who utilized field diaries to record their impressions during data collection through interviews (older individuals (or their proxies), caregivers, and LTCF coordinators) and oral examinations of the older people participants. Additionally, researchers responded to open-ended questions about their experiences. The collected material was subjected to content analysis by two researchers.

Results

The themes that emerged from the analysis were institutional context, aspects affecting the operationalization of the study, and data collection oriented by the clinical-functional profile of the older people. According to the researchers’ perceptions, LTCF coordinators demonstrated concern for the study’s benefits for older adults and the preservation of institutional routines during the research process. Caregivers emerged as vital sources of information, guiding researchers in navigating the challenges posed by the physical and mental complexities of the older people participants, necessitating empathy, sensitivity, and attentive listening from the researchers. The organization of materials and a streamlined data collection process proved essential for optimizing time efficiency and reducing stress for participants and researchers.

Conclusion

The researchers recognized the important role played by LTCF coordinators and formal caregivers, underscoring the significance of empathetic methodologies and streamlined data collection processes in mitigating the challenges inherent to research conducted within LTCFs.
Unlocking timely palliative care: assessing referral practices and barriers at a ghanaian teaching hospital
Authors: Quaidoo Tabitha Gyanewaa , Adu Barbara , Iddrisu Merri , Osei-Tutu Frema , Baaba Candace , Quiadoo Yekua , Poku Collins Atta
Published: April 2024

Background

The need for primary care physicians to be heavily involved in the provision of palliative care is growing. International agencies and practice standards advocate for early palliative care and the use of specialized palliative care services for patients with life-threatening illnesses. This study was conducted to investigate physicians’ referral practices and perceived barriers to timely referral at the Korle Bu Teaching Hospital.

Methods

A cross-sectional study design was employed using a convenience sampling technique to recruit 153 physicians for the study. Data on socio-demography, referral practices, timing and perceived barriers were collected using a structured questionnaire. Binary Logistic regression using crude and adjusted odds was performed to determine the factors associated with late referral. Significance was set at p < 0.05.

Results

The prevalence of late referral was reported to be 68.0%. There were poor referral practices among physicians to palliative care services, and the major barriers to late referral were attributed to the perception that referring to a palliative care specialist means that the physician has abandoned his patient and family members’ decisions and physicians’ personnel choices or opinions on palliative care.

Conclusion

The healthcare system needs tailored interventions targeted at improving physicians’ knowledge and communication strategies, as well as tackling systemic deficiencies to facilitate early and appropriate palliative care referrals. It is recommended that educational programs be implemented, palliative care training be integrated into medical curricula and culturally sensitive approaches be developed to address misconceptions surrounding end-of-life care.
Comorbidities in women with polycystic ovary syndrome: a sibling study
Authors: Boldis Beata Vivien , Grünberger Ilona , Cederström Agneta , Björk Jonas , Nilsson Anton , Helgertz Jonas
Published: April 2024

Background

Polycystic ovary syndrome (PCOS) has previously been associated with several comorbidities that may have shared genetic, epigenetic, developmental or environmental origins. PCOS may be influenced by prenatal androgen excess, poor intrauterine or childhood environmental factors, childhood obesity and learned health risk behaviors. We analyzed the association between PCOS and several relevant comorbidities while adjusting for early-life biological and socioeconomic conditions, also investigating the extent to which the association is affected by familial risk factors.

Methods

This total-population register-based cohort study included 333,999 full sisters, born between 1962 and 1980. PCOS and comorbidity diagnoses were measured at age 17-45 years through national hospital register data from 1997 to 2011, and complemented with information on the study subjects´ early-life and social characteristics. In the main analysis, sister fixed effects (FE) models were used to control for all time-invariant factors that are shared among sisters, thereby testing whether the association between PCOS and examined comorbidities is influenced by unobserved familial environmental, social or genetic factors.

Results

Three thousand five hundred seventy women in the Sister sample were diagnosed with PCOS, of whom 14% had obesity, 8% had depression, 7% had anxiety and 4% experienced sleeping, sexual and eating disorders (SSE). Having PCOS increased the odds of obesity nearly 6-fold (adjusted OR (aOR): 5.9 [95% CI:5.4-6.5]). This association was attenuated in models accounting for unobserved characteristics shared between full sisters, but remained considerable in size (Sister FE: aOR: 4.5 [95% CI: 3.6-5.6]). For depression (Sister FE: aOR: 1.4 [95% CI: 1.2-1.8]) and anxiety (Sister FE: aOR: 1.5 [95% CI: 1.2-1.8), there was a small decrease in the aORs when controlling for factors shared between sisters. Being diagnosed with SSE disorders yielded a 2.4 aOR (95% CI:2.0-2.6) when controlling for a comprehensive set of individual-level confounders, which only decreased slightly when controlling for factors at the family level such as shared genes or parenting style. Accounting for differences between sisters in observed early-life circumstances influenced the estimated associations marginally.

Conclusion

Having been diagnosed with PCOS is associated with a markedly increased risk of obesity and sleeping, sexual and eating disorders, also after accounting for factors shared between sisters and early-life conditions.
Availability and readiness of healthcare facilities and their effects on antenatal care services uptake in Bangladesh
Authors: Khan Md. Nuruzzaman , Alam Md. Badsha , Chowdhury Atika Rahman , Kabir Md. Awal , Khan Md. Mostaured Ali
Published: April 2024

Background

Sustainable Development Goal (SDG) 3.7 aims to ensure universal access to sexual and reproductive healthcare services, where antenatal care (ANC) is a core component. This study aimed to examine the influence of health facility availability and readiness on the uptake of four or more ANC visits in Bangladesh.

Methods

The 2017/18 Bangladesh Demographic and Health Survey data were linked with the 2017 Health Facility Survey and analyzed in this study. The associations of health facility-level factors with the recommended number of ANC uptakes were determined. A multilevel mixed-effect logistic regression model was used to determine the association, adjusting for potential confounders.

Results

Nearly 44% of mothers reported four or more ANC uptakes, with significant variations across several areas in Bangladesh. The average distance of mothers' homes from the nearest health facilities was 6.36 km, higher in Sylhet division (8.25 km) and lower in Dhaka division (4.45 km). The overall uptake of the recommended number of ANC visits was positively associated with higher scores for the management (adjusted odds ratio (aOR) 1.85; 95% CI, 1.16–2.82) and infrastructure (aOR, 1.59; 95% CI, 1.09–2.19) of health facilities closest to mothers' homes. The odds of using the recommended number of ANC in mothers increased by 3.02 (95% CI, 2.01–4.19) and 2.36 (95% CI, 2.09–3.16) folds for each unit increase in the availability and readiness scores to provide ANC services at the closest health facilities, respectively. Every kilometer increase in the average regional-level distance between mothers' homes and the nearest health facilities reduced the likelihood of receiving the recommended number of ANC visits by nearly 42% (aOR, 0.58, 95% CI, 0.42–0.74).

Conclusion

The availability of healthcare facilities close to residence, as well as their improved management, infrastructure, and readiness to provide ANC, plays a crucial role in increasing ANC services uptake. Policies and programs should prioritize increasing the availability, accessibility, and readiness of health facilities to provide ANC services.
GGT5 facilitates migration and invasion through the induction of epithelial–mesenchymal transformation in gastric cancer
Authors: Luo Zhuang , Chen Yong , Chen Bangquan , Zhao Ziming , Wu Rongfan , Ren Jun
Published: April 2024

Background

Gamma-glutamyltransferase 5 (GGT5), one of the two members in the GGT family (GGT1 and GGT5), plays a crucial role in oxidative regulation, inflammation promotion, and drug metabolism. Particularly in the tumorigenesis of various cancers, its significance has been recognized. Nevertheless, GGT5’s role in gastric cancer (GC) remains ambiguous. This study delves into the function and prognostic significance of GGT5 in GC through a series of in vitro experiments.

Methods

Employing online bioinformatics analysis tools such as The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Kaplan–Meier plotter, and cBioPortal, we explored GGT5 characteristics and functions in GC. This encompassed aberrant expression, prognostic value, genomic alterations and mutations, immune cell infiltration, and associated signaling pathways. Immunohistochemistry was conducted to assess GGT5 expression in GC and adjacent normal tissues. Subsequently, univariate and multivariate logistic regression analyses were applied to investigate the associations between GGT5 and clinical characteristics. CCK8, wound healing, and migration assays were utilized to evaluate the impact of GGT5 on cell viability and migration. Additionally, Gene Set Enrichment Analysis (GSEA) and Western blot analysis were performed to scrutinize the activity of the epithelial–mesenchymal transformation (EMT) signaling pathway under GGT5 regulation.

Results

GGT5 exhibits upregulation in gastric cancer, with its overexpression significantly linked to histological differentiation in GC patients (P < 0.05). Multivariate analysis indicates that elevated GGT5 expression is an independent risk factor associated with poorer overall survival in gastric cancer patients (P < 0.05). In vitro experiments reveal that downregulation of GGT5 hampers the proliferation and migration of GC cell lines. Finally, GSEA using TCGA data highlights a significant correlation between GGT5 expression and genes associated with EMT, a finding further confirmed by Western blot analysis.

Conclusions

GGT5 emerges as a promising prognostic biomarker and potential therapeutic target for GC.
Oral-gut microbial transmission promotes diabetic coronary heart disease
Authors: Li Yiwen , Liu Yanfei , Cui Jing , Zhu Mengmeng , Wang Wenting , Chen Keji , Huang Luqi , Liu Yue
Published: April 2024

Background

Diabetes is a predominant driver of coronary artery disease worldwide. This study aims to unravel the distinct characteristics of oral and gut microbiota in diabetic coronary heart disease (DCHD). Simultaneously, we aim to establish a causal link between the diabetes-driven oral-gut microbiota axis and increased susceptibility to diabetic myocardial ischemia–reperfusion injury (MIRI).

Methods

We comprehensively investigated the microbial landscape in the oral and gut microbiota in DCHD using a discovery cohort (n = 183) and a validation chohort (n = 68). Systematically obtained oral (tongue-coating) and fecal specimens were subjected to metagenomic sequencing and qPCR analysis, respectively, to holistically characterize the microbial consortia. Next, we induced diabetic MIRI by administering streptozotocin to C57BL/6 mice and subsequently investigated the potential mechanisms of the oral-gut microbiota axis through antibiotic pre-treatment followed by gavage with specific bacterial strains (Fusobacterium nucleatum or fecal microbiota from DCHD patients) to C57BL/6 mice.

Results

Specific microbial signatures such as oral Fusobacterium nucleatum and gut Lactobacillus, Eubacterium, and Roseburia faecis, were identified as potential microbial biomarkers in DCHD. We further validated that oral Fusobacterium nucleatum and gut Lactobacillus are increased in DCHD patients, with a positive correlation between the two. Experimental evidence revealed that in hyperglycemic mice, augmented Fusobacterium nucleatum levels in the oral cavity were accompanied by an imbalance in the oral-gut axis, characterized by an increased coexistence of Fusobacterium nucleatum and Lactobacillus, along with elevated cardiac miRNA-21 and a greater extent of myocardial damage indicated by TTC, HE, TUNEL staining, all of which contributed to exacerbated MIRI.

Conclusion

Our findings not only uncover dysregulation of the oral-gut microbiota axis in diabetes patients but also highlight the pivotal intermediary role of the increased abundance of oral F. nucleatum and gut Lactobacillus in exacerbating MIRI. Targeting the oral-gut microbiota axis emerges as a potent strategy for preventing and treating DCHD. Oral-gut microbial transmission constitutes an intermediate mechanism by which diabetes influences myocardial injury, offering new insights into preventing acute events in diabetic patients with coronary heart disease.

Graphic Abstract
Development of a multiplex droplet digital PCR method for detection and monitoring of Mycobacterium tuberculosis and drug-resistant tuberculosis
Authors: Choi Yu Jeong , Kim Yoonjung , Park Hye Jung , Kim Dokyun , Lee Hyukmin , Kim Young Ah , Lee Kyung-A
Published: April 2024

Background

The prevalence of multidrug-resistant tuberculosis (MDR-TB) among Korean tuberculosis patients is about 4.1%, which is higher than the OECD average of 2.6%. Inadequate drug use and poor patient compliance increase MDR-TB prevalence through selective pressure. Therefore, prompt detection of drug resistance in tuberculosis patients at the time of diagnosis and quantitative monitoring of these resistant strains during treatment are crucial.

Methods

A multiplex droplet digital PCR (ddPCR) assay was developed and assessed using DNA material of nine Mycobacterium tuberculosis strains with known mutation status that were purchased from the Korean National Tuberculosis Association. We collected a total of 18 MDR-TB residual samples referred for PCR analysis. Total DNA was extracted from the samples and subjected to the quadruplex ddPCR assay. Their results were compared to those of known resistance phenotypes.

Results

The analytical sensitivity and specificity of the multiplex ddPCR assay for detecting INH, RIF, EMB, FQ, and SM resistance-causing mutations ranged from 71.43 to 100% and 94.12–100%, respectively. Follow-up sample results showed that the quadruplex ddPCR assay was sensitive enough to detect IS6110 and other mutations even after onset of treatment.

Conclusions

We developed a sensitive and accurate multiplex ddPCR assay that can detect the presence of tuberculosis quantitatively and resistance-conveying mutations concurrently. This tool could aid clinicians in the diagnosis and treatment monitoring of tuberculosis.
A macrophage-cell model of HIV latency reveals the unusual importance of the bromodomain axis
Authors: Kisaka Javan K. , Rauch Daniel , Griffith Malachi , Kyei George B.
Published: April 2024

Background

Although macrophages are now recognized as an essential part of the HIV latent reservoir, whether and how viral latency is established and reactivated in these cell types is poorly understood. To understand the fundamental mechanisms of viral latency in macrophages, there is an urgent need to develop latency models amenable to genetic manipulations and screening for appropriate latency-reversing agents (LRAs). Given that differentiated THP-1 cells resemble monocyte-derived macrophages in HIV replication mechanisms, we set out to establish a macrophage cell model for HIV latency using THP-1 cells.

Methods

We created single-cell clones of THP-1 cells infected with a single copy of the dual-labeled HIVGKO in which a codon switched eGFP (csGFP) is under the control of the HIV-1 5’ LTR promoter, and a monomeric Kusabira orange 2 (mKO2) under the control of cellular elongation factor one alpha promoter (EF1α). Latently infected cells are csGFP−, mKO2+, while cells with actively replicating HIV (or reactivated virus) are csGFP+,mKO2+. After sorting for latently infected cells, each of the THP-1 clones with unique integration sites for HIV was differentiated into macrophage-like cells with phorbol 12-myristate 13-acetate (PMA) and treated with established LRAs to stimulate HIV reactivation. Monocyte-derived macrophages (MDMs) harboring single copies of HIVGKO were used to confirm our findings.

Results

We obtained clones of THP-1 cells with latently infected HIV with unique integration sites. When the differentiated THP-1 or primary MDMs cells were treated with various LRAs, the bromodomain inhibitors JQ1 and I-BET151 were the most potent compounds. Knockdown of BRD4, the target of JQ1, resulted in increased reactivation, thus confirming the pharmacological effect. The DYRK1A inhibitor Harmine and lipopolysaccharide (LPS) also showed significant reactivation across all three MDM donors. Remarkably, LRAs like PMA/ionomycin, bryostatin-1, and histone deacetylase inhibitors known to potently reactivate latent HIV in CD4 + T cells showed little activity in macrophages.

Conclusions

Our results indicate that this model could be used to screen for appropriate LRAs for macrophages and show that HIV latency and reactivation mechanisms in macrophages may be distinct from those of CD4 + T cells.
Regulatory T cells limit age-associated retinal inflammation and neurodegeneration
Authors: Llorián-Salvador María , de la Fuente Alerie G. , McMurran Christopher E. , Dashwood Amy , Dooley James , Liston Adrian , Penalva Rosana , Dombrowski Yvonne , Stitt Alan W. , Fitzgerald Denise C.
Published: April 2024

Background

Ageing is the principal risk factor for retinal degenerative diseases, which are the commonest cause of blindness in the developed countries. These conditions include age-related macular degeneration or diabetic retinopathy. Regulatory T cells play a vital role in immunoregulation of the nervous system by limiting inflammation and tissue damage in health and disease. Because the retina was long-considered an immunoprivileged site, the precise contribution of regulatory T cells in retinal homeostasis and in age-related retinal diseases remains unknown.

Methods

Regulatory T cells were selectively depleted in both young (2–4 months) and aged (18–23 months) FoxP3-DTR mice. We evaluated neuroretinal degeneration, gliosis, subretinal space phagocyte infiltration, and retinal pigmented epithelium morphology through immunofluorescence analysis. Subsequently, aged Treg depleted animals underwent adoptive transfer of both young and aged regulatory T cells from wild-type mice, and the resulting impact on neurodegeneration was assessed. Statistical analyses employed included the U-Mann Whitney test, and for comparisons involving more than two groups, 1-way ANOVA analysis followed by Bonferroni’s post hoc test.

Results

Our study shows that regulatory T cell elimination leads to retinal pigment epithelium cell dysmorphology and accumulation of phagocytes in the subretinal space of young and aged mice. However, only aged mice experience retinal neurodegeneration and gliosis. Surprisingly, adoptive transfer of young but not aged regulatory T cells reverse these changes.

Conclusion

Our findings demonstrate an essential role for regulatory T cells in maintaining age retinal homeostasis and preventing age-related neurodegeneration. This previously undescribed role of regulatory T cells in limiting retinal inflammation, RPE/choroid epithelium damage and subsequently photoreceptor loss with age, opens novel avenues to explore regulatory T cell neuroprotective and anti-inflammatory properties as potential therapeutic approaches for age-related retinal diseases.
Volatile versus propofol sedation after cardiac valve surgery: a single-center prospective randomized controlled trial
Authors: Flinspach Armin Niklas , Raimann Florian Jürgen , Kaiser Philipp , Pfaff Michaela , Zacharowski Kai , Neef Vanessa , Adam Elisabeth Hannah
Published: April 2024

Background

Optimal intensive care of patients undergoing valve surgery is a complex balancing act between sedation for monitoring and timely postoperative awakening. It remains unclear, if these requirements can be fulfilled by volatile sedations in intensive care medicine in an efficient manner. Therefore, this study aimed to assess the time to extubation and secondary the workload required.

Methods

We conducted a prospective randomized single-center trial at a tertiary university hospital to evaluate the postoperative management of open valve surgery patients. The study was randomized with regard to the use of volatile sedation compared to propofol sedation. Sedation was discontinued 60 min after admission for critical postoperative monitoring.

Results

We observed a significantly earlier extubation (91 ± 39 min vs. 167 ± 77 min; p < 0.001), eye-opening (86 ± 28 min vs. 151 ± 71 min; p < 0.001) and command compliance (93 ± 38 min vs. 164 ± 75 min; p < 0.001) using volatile sedation, which in turn was associated with a significantly increased workload of a median of 9:56 min (± 4:16 min) set-up time. We did not observe any differences in complications. Cardiopulmonary bypass time did not differ between the groups 101 (IQR 81; 113) versus 112 (IQR 79; 136) minutes p = 0.36.

Conclusions

Using volatile sedation is associated with few minutes additional workload in assembling and enables a significantly accelerated evaluation of vulnerable patient groups. Volatile sedation has considerable advantages and emerges as a safe sedation technique in our vulnerable study population.

Trial registration: Clinical trials registration (NCT04958668) was completed on 1 July 2021.