bluuebunny/crossref_metadata_2025 huggingface dataset:
Sequenced-based GWAS for linear classification traits in Belgian Blue beef cattle reveals new coding variants in genes regulating body size in mammals
Authors: Gualdrón Duarte José Luis , Yuan Can , Gori Ann-Stephan , Moreira Gabriel C. M. , Takeda Haruko , Coppieters Wouter , Charlier Carole , Georges Michel , Druet Tom
Published: November 2023

Background

Cohorts of individuals that have been genotyped and phenotyped for genomic selection programs offer the opportunity to better understand genetic variation associated with complex traits. Here, we performed an association study for traits related to body size and muscular development in intensively selected beef cattle. We leveraged multiple trait information to refine and interpret the significant associations.

Results

After a multiple-step genotype imputation to the sequence-level for 14,762 Belgian Blue beef (BBB) cows, we performed a genome-wide association study (GWAS) for 11 traits related to muscular development and body size. The 37 identified genome-wide significant quantitative trait loci (QTL) could be condensed in 11 unique QTL regions based on their position. Evidence for pleiotropic effects was found in most of these regions (e.g., correlated association signals, overlap between credible sets (CS) of candidate variants). Thus, we applied a multiple-trait approach to combine information from different traits to refine the CS. In several QTL regions, we identified strong candidate genes known to be related to growth and height in other species such as LCORL-NCAPG or CCND2. For some of these genes, relevant candidate variants were identified in the CS, including three new missense variants in EZH2, PAPPA2 and ADAM12, possibly two additional coding variants in LCORL, and candidate regulatory variants linked to CCND2 and ARMC12. Strikingly, four other QTL regions associated with dimension or muscular development traits were related to five (recessive) deleterious coding variants previously identified.

Conclusions

Our study further supports that a set of common genes controls body size across mammalian species. In particular, we added new genes to the list of those associated with height in both humans and cattle. We also identified new strong candidate causal variants in some of these genes, strengthening the evidence of their causality. Several breed-specific recessive deleterious variants were identified in our QTL regions, probably as a result of the extreme selection for muscular development in BBB cattle.
Identification of HpMYB1 inducing anthocyanin accumulation in Hippeastrum Hybridum tepals by RNA-seq
Authors: Li Ji , Wu Kunlin , Li Lin , Ma Guohua , Fang Lin , Zeng Songjun
Published: November 2023

Background

Cultivated Hippeastrum × hybridum is a popular ornamental plant with large and colorful flowers, long flowering duration, and high commercial value. As its main ornamental feature, its flower color is related to the anthocyanin content in the tepals. However, the molecular regulatory mechanisms of anthocyanin biosynthesis in H. × hybridum have not yet been elucidated.

Results

In the present study, 12 cDNA libraries of four stages of H.× hybridum ‘Royal Velvet’ tepal development were used for RNA-seq, obtaining 79.83 gigabases (GB) of clean data. The data were assembled into 148,453 unigenes, and 11,262 differentially expressed genes were identified. Forty key enzymes participating in anthocyanin biosynthesis were investigated, and the results showed that most of the anthocyanin structural genes were expressed at low levels in S1 and were markedly upregulated in S2 and S3. The expression profiles of 12 selected genes were verified by qRT-PCR. Furthermore, the R2R3-MYB transcription factor (TF), HpMYB1, involved in the regulation of anthocyanin biosynthesis was identified by sequence, expression pattern, and subcellular localization analyses. Its overexpression in tobacco significantly increased the anthocyanin levels in various tissues and activated anthocyanin-related genes.

Conclusions

Using RNA-seq technology, we successfully identified a potential R2R3-MYB gene, HpMYB1, that regulates anthocyanin biosynthesis in H.× hybridum ‘Royal Velvet’. Our findings provide basic transcript information and valuable transcriptome data for further identification of key genes involved in anthocyanin biosynthesis and can be applied in the artificial breeding of new H. × hybridum cultivars with enhanced ornamental value.
Endoscopic and histopathological hints on infections in patients of common variable immunodeficiency disorder with gastrointestinal symptoms
Authors: Chen Yang , You Yan , Li Ji , Yang Aiming , Zhou Weixun , Li Xiaoqing
Published: November 2023

Background and aims

Common variable immunodeficiency disorder (CVID) patients may have gastrointestinal (GI) involvement and suffer from infections, which are poorly understood. This study aimed to evaluate the clinical, endoscopic, and histopathological features of CVID patients with GI symptoms and determine their correlation with infections.

Methods

We performed a retrospective study on 21 CVID patients with GI symptoms who underwent endoscopic examination in Peking Union Medical College Hospital from 2000 to 2020. The clinical, infectious, endoscopic, and histopathological features were reassessed.

Results

Chronic diarrhea was the most prevalent GI symptom, observed in 95.2% of our CVID cohort. Over 85% of patients had low body weight and malabsorption. Small bowel villous atrophy was found in 90.5% of patients under endoscopy and mostly confirmed by histopathology. GI infections were identified in 9 (42.9%) patients. Of these, 7 patients with diffuse and obvious nodular lymphoid hyperplasia (NLH) of small bowel under endoscopy had significantly higher infection rate (85.7% vs 21.4%, p < 0.05), predominantly with Giardia and bacteria. Small bowel biopsies showed 95% of patients lacked plasma cells and 60% had increased intraepithelial lymphocytes (IELs), but not significantly different between GI infection and non-infection group. Most patients improved after intravenous immunoglobulin and anti-infection therapy.

Conclusions

CVID could involve GI tract, particularly small bowel. Obvious NLH under endoscopy could be a hint for GI infection in CVID patients. Comprehensive endoscopic and histopathological evaluation may be helpful in CVID diagnosis and identification of potential co-infection, leading to proper treatment.
A rapid review of antenatal hepatitis C virus testing in the United Kingdom
Authors: Hibbert M. P. , Simmons R. , Mandal S. , Sabin C. A. , Desai M.
Published: November 2023

Background

The United Kingdom (UK) has committed to the World Health Organization’s viral hepatitis elimination targets. New case finding strategies, such as antenatal testing, may be needed to achieve these targets. We conducted a rapid review to understand hepatitis C-specific antibody (anti-HCV) and HCV RNA test positivity in antenatal settings in the United Kingdom to inform guidance.

Methods

Articles and conference abstracts published between January 2000 and June 2022 reporting anti-HCV testing in antenatal settings were identified through PubMed and Web of Science searches. Results were synthesised using a narrative approach.

Results

The search identified 2,011 publications; 10 studies were included in the final synthesis. Seven studies used anonymous testing methods and three studies used universal opt-out testing. Anti-HCV test positivity ranged from 0.1 to 0.99%, with a median value of 0.38%. Five studies reported HCV RNA positivity, which ranged from 0.1 to 0.57% of the testing population, with a median value of 0.22%. One study reported cost effectiveness of HCV and found it to be cost effective at £9,139 per quality adjusted life years.

Conclusion

The relative contribution of universal opt-out antenatal testing for HCV should be reconsidered, as antenatal testing could play an important role in new case-finding and aid achieving elimination targets.
TIGIT+ NK cells in combination with specific gut microbiota features predict response to checkpoint inhibitor therapy in melanoma patients
Authors: Tsakmaklis Anastasia , Farowski Fedja , Zenner Rafael , Lesker Till Robin , Strowig Till , Schlößer Hans , Lehmann Jonas , von Bergwelt-Baildon Michael , Mauch Cornelia , Schlaak Max , Knuever Jana , Schweinsberg Viola , Heinzerling Lucie M. , Vehreschild Maria J. G. T.
Published: November 2023

Background

Composition of the intestinal microbiota has been correlated to therapeutic efficacy of immune checkpoint inhibitors (ICI) in various cancer entities including melanoma. Prediction of the outcome of such therapy, however, is still unavailable. This prospective, non-interventional study was conducted in order to achieve an integrated assessment of the connection between a specific intestinal microbiota profile and antitumor immune response to immune checkpoint inhibitor therapy (anti-PD-1 and/or anti-CTLA-4) in melanoma patients.

Methods

We assessed blood and stool samples of 29 cutaneous melanoma patients who received immune checkpoint inhibitor therapy. For functional and phenotypical immune analysis, 12-color flow cytometry and FluoroSpot assays were conducted. Gut microbiome was analyzed with shotgun metagenomics sequencing. To combine clinical, microbiome and immune variables, we applied the Random Forest algorithm.

Results

A total of 29 patients was analyzed in this study, among whom 51.7% (n = 15) reached a durable clinical benefit. The Immune receptor TIGIT is significantly upregulated in T cells (p = 0.0139) and CD56high NK cells (p = 0.0037) of responders. Several bacterial taxa were associated with response (e.g. Ruminococcus torques) or failure (e.g. Barnesiella intestinihominis) to immune therapy. A combination of two microbiome features (Barnesiella intestinihominis and the Enterobacteriaceae family) and one immune feature (TIGIT+ CD56high NK cells) was able to predict response to ICI already at baseline (AUC = 0.85; 95% CI: 0.841–0.853).

Conclusions

Our results reconfirm a link between intestinal microbiota and response to ICI therapy in melanoma patients and furthermore point to TIGIT as a promising target for future immunotherapies.
Higher global diet quality score is related to lower prevalence of depression and poor quality of life among adolescent girls
Authors: Beigrezaei Sara , Darabi Zahra , Davies Ian G. , Mazidi Mohsen , Ghayour-Mobarhan Majid , Khayyatzadeh Sayyed Saeid
Published: November 2023

Background

Adolescence is a key time for the development of depression symptoms and the diet quality may be associated with mental health conditions. The present study examined the association between depression and quality of life (QoL) and the global diet quality score (GDQS) as a simple and standardized metric diet quality in Iranian adolescents.

Methods

This cross-sectional study was conducted on 733 adolescent girls recruited using a random cluster sampling method. A 147-item food frequency questionnaire (FFQ) was used for dietary intake assessment. The GDQS is gained by summing points of all the 25 food groups, ranged from 0 to 49. Depression symptoms were assessed using a Persian version of the Beck Depression Inventory (BDI). For assessment of health-related QoL, the Short Form 12 Survey–version 2 (SF-12v2) questionnaire was employed. Multivariable logistic regression examined the association of depression and QoL with GDQS in crude and adjusted models.

Results

Adolescent girls in the highest tertile of GDQS score compared with the lowest tertile had a 41% lower odds of depressive symptoms (OR: 0.59; 95% CI: 0.39–0.90, P = 0.01). The participants in the third tertile of GDQS score had lower odds of poor QoL compared with the first tertile (OR: 0.56; 95% CI: 0.37–0.85, P < 0.01). These associations remained significant (both P = 0.01) after adjustment for age, energy intake, body mass index (BMI), physical activity, and menstruation (depressive symptoms: OR: 0.59; 95% CI: 0.38–0.92; QoL: OR: 0.59; 95% CI: 0.38–0.91, P = 0.01).

Conclusion

We found that adolescent girls with a higher score of the GDQS had lower odds of depression and poor QoL Prospective and interventional investigations are needed to reach a clear vision.
Understanding COVID-19 vaccine hesitancy in the Hispanic adult population of South Carolina: a complex mixed-method design evaluation study
Authors: Rossi Maria Mercedes , Parisi Michelle A. , Cartmell Kathleen B. , McFall Danielle
Published: November 2023

Background

In August 2021, only 47.6% of all eligible residents in South Carolina (SC) had received at least one dose of the COVID-19 vaccine, with only 41% having completed their vaccination series. Additionally, only 27% of all Hispanics in SC had completed their vaccination series compared to 34.1% of non-Hispanics. Vaccine hesitancy is a complex phenomenon that is context and vaccine-specific. Focusing on unvaccinated Hispanics living in rural areas of SC, this study aimed to identify barriers to vaccination and provide an educational intervention designed to address vaccine hesitancy.

Methods

A complex mixed-methods evaluation design was used to conduct this study. First, in-person vaccine educational sessions were implemented, along with a pre-post-test survey, to assess changes in knowledge, attitudes, motivations, barriers, and intentions to receive COVID-19 vaccination. Second, in-person follow-up focus groups were held with the same participants to gather in-depth insight about participants’ knowledge and attitudes about the COVID-19 vaccination. Third, an online follow-up survey was conducted to assess the effect of the training and discussion session on COVID-19 vaccination. Study outcomes were assessed among the 17 individuals who participated in the educational sessions and focus group discussions.

Results

Findings revealed that for unvaccinated Hispanics living in South Carolina; vaccine hesitancy was primarily driven by: 1) misinformation and information coming from unverified sources and 2) negative perceptions of the safety and effectiveness of the COVID-19 vaccines. Specifically, participants were fearful that the vaccine development was rushed and that the vaccines might contain questionable ingredients that could cause strong side effects or even death. Participants were also concerned that vaccination might cause them to get sick and be hospitalized, which would have financial implications since they could not afford healthcare or take time off work.

Conclusions

Program implementation and mass communication campaigns should focus on COVID-19 vaccine safety and effectiveness, including side effects, what to expect after being vaccinated, and how to look for information from reputable sources. The educational session implemented proved to be effective and helped reduce vaccine hesitancy since most participants (80%) self-reported receiving a COVID-19 vaccine after program participation.
Using intra-breath oscillometry in obesity hypoventilation syndrome to detect tidal expiratory flow limitation: a potential marker to optimize CPAP therapy
Authors: Baglyas Szabolcs , Valkó Luca , Móró Vivien , Podmaniczky Eszter , Czövek Dorottya , Makan Gergely , Gingl Zoltán , Gál János , Hantos Zoltán , Lorx András
Published: November 2023

Background

Continuous positive airway pressure (CPAP) therapy has profound effects in obesity hypoventilation syndrome (OHS). Current therapy initiation focuses on upper airway patency rather than the assessment of altered respiratory mechanics due to increased extrapulmonary mechanical load.

Methods

We aimed to examine the viability of intra-breath oscillometry in optimizing CPAP therapy for OHS. We performed intra-breath oscillometry at 10 Hz in the sitting and supine positions, followed by measurements at increasing CPAP levels (none-5-10-15-20 cmH2O) in awake OHS patients. We plotted intra-breath resistance and reactance (Xrs) values against flow (V’) and volume (V) to identify tidal expiratory flow limitation (tEFL).

Results

Thirty-five patients (65.7% male) completed the study. We found a characteristic looping of the Xrs vs V’ plot in all patients in the supine position revealing tEFL: Xrs fell with decreasing flow at end-expiration. Intra-breath variables representing expiratory decrease of Xrs became more negative in the supine position [end-expiratory Xrs (mean ± SD): -1.9 ± 1.8 cmH2O·s·L− 1 sitting vs. -4.2 ± 2.2 cmH2O·s·L− 1 supine; difference between end-expiratory and end-inspiratory Xrs: -1.3 ± 1.7 cmH2O·s·L− 1 sitting vs. -3.6 ± 2.0 cmH2O·s·L− 1 supine, p < 0.001]. Increasing CPAP altered expiratory Xrs values and loop areas, suggesting diminished tEFL (p < 0.001). ‘Optimal CPAP’ value (able to cease tEFL) was 14.8 ± 4.1 cmH2O in our cohort, close to the long-term support average of 13.01(± 2.97) cmH2O but not correlated. We found no correlation between forced spirometry values, patient characteristics, apnea-hypopnea index and intra-breath oscillometry variables.

Conclusions

tEFL, worsened by the supine position, can be diminished by stepwise CPAP application in most patients. Intra-breath oscillometry is a viable method to detect tEFL during CPAP initiation in OHS patients and tEFL is a possible target for optimizing therapy in OHS patients.
Marginal adaptation, physicochemical and rheological properties of treated dentin matrix hydrogel as a novel injectable pulp capping material for dentin regeneration
Authors: Holiel Ahmed A. , Sedek Eman M.
Published: November 2023

Background

Treated dentin matrix hydrogel (TDMH) has been introduced as a novel injectable direct pulp capping material. In this regard, this study aimed to evaluate its marginal adaptation, physicochemical and rheological properties for the development of clinically feasible TDMH.

Methods

TDMH was applied to the pulp floor of prepared Class I cavities (n = 5), marginal adaptation was assessed by SEM at 1000 X magnification to detect gap between dentin and filling material. Five syringes were filled with TDMH and placed between the compression plates of a universal testing machine to evaluate injectability and gelation time was also evaluated by test vial inverting method. The microstructures of lyophilized TDMH were observed by SEM. Moreover, TDMH discs (n = 5) were prepared and the water uptake (%) was determined based on the equilibrium swelling theory state of hydrogels. Its solubility was measured after one week by the ISO standard method. Rheological behaviours of TDMH (n = 5) were analysed with a rotational rheometer by computing their complex shear modulus G* and their associated storage modulus (G′) and loss modulus (G′’). Statistical analysis was performed using F test (ANOVA) with repeated measures and Post Hoc Test (p = 0.05).

Results

TDMH presented an overall 92.20 ± 2.95% of continuous margins. It exhibited gelation during the first minute, and injectability mean was 66 ± 0.36%. TDMH showed a highly porous structure, and the pores were interconnected with an average diameter about 5.09 ± 3.17 μm. Swelling equilibrium gradually reached at 6 days up to 377%. The prepared hydrogels and maintained their shape after absorbing over three times their original weight of water. TDMH fulfilled the requirements of ISO 6876, demonstrating a weight loss of 1.98 ± 0.09% and linear viscoelastic behaviour with G` 479.2 ± 12.7 and G`` 230.8 ± 13.8.

Conclusions

TDMH provided good marginal adaptation, appropriate physicochemical and viscoelastic properties support its use as a novel direct pulp capping material in future clinical applications.
Successful complete oral rehabilitation of a patient with osteopetrosis with extensive pre-treatments, bone grafts, dental implants and fixed bridges: a multidisciplinary case report
Authors: Kelk P. , Fasth A. , Holgerson PLif , Sjöström M.
Published: November 2023

Background

Osteopetrosis comprises a group of inherited disorders that are rare and result in abnormal bone structure. Bone remodeling is extremely inhibited because osteoclasts are nonfunctional or lacking. This condition causes overgrowth of bone with disappearance of the bone marrow, leading to aplastic anemia; obstruction of nerve passages in the skull leads to blindness and often hearing impairment. In most cases, osteopetrosis results in oral complications such as tooth deformation, hypomineralization, and delayed or absent tooth eruption. The only curative treatment is hematopoietic stem cell transplantation (HSCT). The main treatment of the oral complications during childhood and adolescence consists in protecting the erupted teeth against caries disease through prophylactic treatment aimed at optimal oral hygiene through frequent regular dental visits throughout life. Many patients with osteopetrosis require major oral rehabilitation to treat complications of the disease. Improved results of HSCT increase the likelihood that dental professionals will encounter patients with osteopetrosis.

Case presentation

In this case report, we show that individuals with osteopetrosis who have severe oral complications can be treated successfully if they are treated for osteopetrosis at an early age. The boy had his dental care in pedodontics, and regular multidisciplinary meetings were held for future treatment planning. At the age of 15, he was then referred for rehabilitation. The initial evaluations revealed no further growth in the alveolar bone. The rehabilitation was done stepwise, with extraction of malformed and malpositioned teeth. Initially, the patient received a removable partial denture followed by reconstruction of the width of the alveolar process, titanium implants, temporary fixed bridges, and finally screw-retained titanium–ceramic bridges with titanium frames for the upper and lower jaws.

Conclusions

The three-year follow-up after loading indicated a stable marginal bone level and optimal oral hygiene as a result of frequent professional oral hygiene care. The patient showed no signs of symptoms from the temporomandibular joint and has adapted to the new jaw relation without any functional or phonetical issues.
Palliative care research utilising intersectionality: a scoping review
Authors: Butler Helen , Gott Merryn , Prebble Doctor Kate , Fortune Doctor Sarah , Robinson Doctor Jackie
Published: November 2023

Background

Access to palliative care is recognised as a human right, yet clear disparities exist. There have been recent appeals to examine people’s contexts and interactions with social systems which for many, adversely influence their utilisation of palliative care. Intersectionality provides a way to understand these drivers of inequity and ultimately advocate for change.

Aim

To identify and describe published studies utilising intersectionality in relation to need, access and experience of palliative care.

Design

A scoping review.

Data sources

Medline, PsycINFO, CINAHL and Google Scholar databases and a manual search were undertaken for studies published up to January 2023. Included studies were evidence based articles where palliative or end of life care was the focus and intersectionality was identified and/or applied to the research that was undertaken.

Results

Ten published studies were included. An analytic framework was developed to identify the extent that intersectionality was utilised in each study. A wide range of different groups were researched across the studies, with most focusing on aspects of their participant’s identity in relation to palliative care access and experience. Common topics of power, heterogeneity of people within the health system and barriers to palliative care were illuminated across the studies.

Conclusions

Very limited research to date has utilised intersectionality to understand access, utilisation and experience of palliative care. This scoping review demonstrates intersectionality can provide a way to illuminate rich understandings of inequity in palliative care. It is imperative that future palliative research incorporates an intersectionality focus to further clarify the needs and experiences of structurally marginalised groups.
Strategy maintenance in smart healthcare systems
Authors: Boujelben Abir , Amous Ikram
Published: November 2023

Backgrounds

The size of medical strategies is expected to grow in conjunction with the expansion of modern diseases’ complexity. When a strategy includes more than ten statements, its manual management becomes very challenging, and in some cases, impossible. As a result, the updates they get may result in the unavoidable appearance of anomalies. This causes an interruption in the outflow of imperfect knowledge.

Methods

In this paper, we propose an approach called TAnom-HS to verify healthcare strategies. We focus on the management and maintenance, in a convenient and automatic way, of a large strategy to guarantee knowledge accuracy and enhance the efficiency of the inference process in healthcare systems.

Results

We developed a prototype of our proposal and we applied it on some cases from the BioPortal repository. The evaluation of both steps of TAnom-HS proved the efficiency of our proposal.

Conclusion

To increase ontologies expressiveness, a set of rules called strategy is added to it. TAnom-HS is a two-step approach that treats anomalies in healthcare strategies. Such a task helps to take automatic and efficient healthcare decisions.
Noggin contributes to brain metastatic colonization of lung cancer cells
Authors: Lee Jung Eun , Park Jihye , Kim Eun Ju , Ko Yoon Ho , Hong Soon Auck , Yang Seung Ho , Ahn Young-Ho
Published: November 2023

Background

Brain metastasis is a common complication among patients with lung cancer, yet the underlying mechanisms remain unclear. In this study, we aimed to investigate the pathogenesis of brain metastasis in lung cancer.

Methods

We established highly colonizing metastatic lung cancer cells, A549-M2, through multiple implantations of A549 human lung cancer cells in the carotid artery of athymic nude mice.

Results

Compared to parental cells (M0), M2 cells demonstrated slower growth in culture plates and soft agar, as well as lower motility and higher adhesion, key characteristics of mesenchymal–epithelial transition (MET). Further analysis revealed that M2 cells exhibited decreased expression of epithelial–mesenchymal transition markers, including ZEB1 and Vimentin. M2 cells also demonstrated reduced invasiveness in co-culture systems. RNA sequencing and gene set enrichment analysis confirmed that M2 cells underwent MET. Intriguingly, depletion of Noggin, a BMP antagonist, was observed in M2 cells, and replenishment of Noggin restored suppressed migration and invasion of M2 cells. In addition, Noggin knockdown in control M0 cells promoted cell attachment and suppressed cell migration, suggesting that Noggin reduction during brain colonization causes inhibition of migration and invasion of metastatic lung cancer cells.

Conclusions

Our results suggest that lung cancer cells undergo MET and lose their motility and invasiveness during brain metastatic colonization, which is dependent on Noggin.
Exploring the promising potential of induced pluripotent stem cells in cancer research and therapy
Authors: Chehelgerdi Matin , Behdarvand Dehkordi Fereshteh , Chehelgerdi Mohammad , Kabiri Hamidreza , Salehian-Dehkordi Hosein , Abdolvand Mohammad , Salmanizadeh Sharareh , Rashidi Mohsen , Niazmand Anoosha , Ahmadi Saba , Feizbakhshan Sara , Kabiri Saber , Vatandoost Nasimeh , Ranjbarnejad Tayebeh
Published: November 2023

The advent of iPSCs has brought about a significant transformation in stem cell research, opening up promising avenues for advancing cancer treatment. The formation of cancer is a multifaceted process influenced by genetic, epigenetic, and environmental factors. iPSCs offer a distinctive platform for investigating the origin of cancer, paving the way for novel approaches to cancer treatment, drug testing, and tailored medical interventions. This review article will provide an overview of the science behind iPSCs, the current limitations and challenges in iPSC-based cancer therapy, the ethical and social implications, and the comparative analysis with other stem cell types for cancer treatment. The article will also discuss the applications of iPSCs in tumorigenesis, the future of iPSCs in tumorigenesis research, and highlight successful case studies utilizing iPSCs in tumorigenesis research. The conclusion will summarize the advancements made in iPSC-based tumorigenesis research and the importance of continued investment in iPSC research to unlock the full potential of these cells.
The development of an integrated neighborhood approach for health promotion and prevention: a qualitative exploration of stakeholders’ views
Authors: Bosdijk Anniek , Nieboer Anna Petra , Cramm Jane Murray
Published: November 2023

Background

Although the promise of integrated neighborhood approaches, including the essential roles of communities and collaboration between the medical and social domains, has been widely acknowledged, the realization of such approaches in practice often remains difficult. To gain insight into the development of integrated neighborhood approaches, this case study describes the experiences of stakeholders involved in such an approach for health promotion and prevention in Rotterdam.

Methods

Interviews with 18 stakeholders (including health and social care professionals, health insurance employees, and policymakers) were conducted, and stakeholders’ statements were analyzed thematically.

Results

The results reveal a lack of alignment among the professional, organizational, and system levels. Elements needed for collaboration between health and social care professionals are not supported at the organizational and system levels. The lack of integration at the policy and organizational levels encourages competition and self-interest instead of stimulating collaboration.

Conclusions

Intersectoral collaboration and coordination must take place not only between professionals, but also at the organizational and policy levels. As long as integration at the organizational and system levels is lacking, professionals’ ability to collaborate and provide coordinated support to neighborhood residents will be compromised.
hnRNPA2B1 promotes the occurrence and progression of hepatocellular carcinoma by downregulating PCK1 mRNA via a m6A RNA methylation manner
Authors: Hao Weijie , Chen Zhimin , Tang Jingzhi , Yang Ru , Gao Wei-Qiang , Xu Huiming
Published: November 2023

Background

N6-methyladenosine (m6A) is the most prevalent RNA modification. Although hnRNPA2B1, as a reader of m6A modification, has been reported to promote tumorigenesis in a few types of tumors, its role in hepatocellular carcinoma (HCC) and the underlying molecular mechanism remains unclear.

Methods

Multiple public databases were used to analyze the expression of hnRNPA2B1 in HCC and its correlation with survival prognosis. We employed a CRISPR-Cas9 sgRNA editing strategy to knockout hnRNPA2B1 expression in HCC cells. The biological function of hnRNPA2B1 in vitro in HCC cells was measured by CCK8, colony formation, migration, and invasion assay. The tumorigenic function of hnRNPA2B1 in vivo was determined by a subcutaneous tumor formation experiment and a HCC mouse model via tail injection of several plasmids into the mouse within 5s-7s. RNA binding protein immunoprecipitation (RIP) experiment using hnRNPA2B1 was performed to test the target genes of hnRNPA2B1 and methylated RNA immunoprecipitation (MeRIP) assay was performed to explore the m6A methylated mRNA of target genes.

Results

hnRNPA2B1 highly expressed in HCC tissues, correlated with high grades and poor prognosis. Its knockout reduced HCC cell proliferation, migration, and invasion in vitro, while overexpression promoted these processes. hnRNPA2B1-knockout cells inhibited tumor formation in graft experiments. In HCC mice, endogenous knockout attenuated hepatocarcinogenesis. RNA-seq showed downregulated gluconeogenesis with high hnRNPA2B1 expression. hnRNPA2B1 negatively correlated with PCK1, a key enzyme. RIP assay revealed hnRNPA2B1 binding to PCK1 mRNA. hnRNPA2B1 knockout increased m6A-methylation of PCK1 mRNA. Interestingly, PCK1 knockout partially counteracted tumor inhibition by hnRNPA2B1 knockout in mice.

Conclusion

Our study indicated that hnRNPA2B1 is highly expressed in HCC and correlated with a poor prognosis. hnRNPA2B1 promotes the tumorigenesis and progression of HCC both in vitro and in vivo. Moreover, hnRNPA2B1 downregulates the expression of PCK1 mRNA via a m6A methylation manner. More importantly, the ability of hnRNPA2B1 to induce tumorigenesis and progression in HCC is dependent on its ability to decrease the expression of PCK1. Therefore, this study suggested that hnRNPA2B1 might be a diagnostic marker of poor prognosis of HCC and a potential therapeutic target for HCC patients.
Sarcomatoid mesothelioma diagnosed in a patient with mesothelioma in situ: a case report on morphologic differences after 9-month interval with details analysis of cytology in early-stage mesothelioma
Authors: Yoshida Miho , Jimbo Naoe , Tsukamoto Ryuko , Itoh Tomoo , Kawahara Kunimitsu , Mitsui Suguru , Tanaka Yugo , Maniwa Yoshimasa
Published: November 2023

Background

Overlapping morphological features of mesothelial cells have been rendered it difficult to distinguish between reactive and malignant conditions. The development of methods based on detecting genomic abnormalities using immunohistochemistry and fluorescence in situ hybridization have contributed markedly to solving this problem. It is important to identify bland mesothelioma cells on cytological screening, perform efficient genomic-based testing, and diagnose mesothelioma, because the first clinical manifestation of pleural mesothelioma is pleural effusion, which is the first sample available for pathological diagnosis. However, certain diagnostic aspects remain challenging even for experts.

Case presentation

This report describes a case of a 72-year-old man with a history of asbestos exposure who presented with pleural effusion as the first symptom and was eventually diagnosed as mesothelioma. Mesothelioma was suspected owing to prominent cell-in-cell engulfment in mesothelial cells on the first cytological sample, and the diagnosis of mesothelioma in situ was confirmed by histology. Unexpectedly, sarcomatoid morphology of mesothelioma was found in the second pathology samples 9 months after the first pathological examination. Both the mesothelioma in situ and invasive lesion showed immunohistochemical loss of methylthioadenosine phosphorylase (MTAP) and homozygous deletion of cyclin dependent kinase inhibitor 2A (CDKN2A) on fluorescence in situ hybridization. The patient received medication therapy but died of disease progression 12 months after the diagnosis of the sarcomatoid morphology of mesothelioma.

Conclusion

Our case suggests that cell-in-cell engulfment can be conspicuous in early-stage mesothelioma with inconspicuous nuclear atypia and few multinucleated cells. In addition, the presence of MTAP loss and CDKN2A homozygous deletion are suspected to be involved in early formation to invasive lesions and/or sarcomatoid morphology. We believe that it is important to consider genetic abnormalities when deciding on individual patient management. Furthermore, cases of mesothelioma, even those of an in situ lesion, with MTAP loss and/or CDKN2A deletion should be carefully followed up or subjected to early treatment.
Extracellular vesicle-packaged circBIRC6 from cancer-associated fibroblasts induce platinum resistance via SUMOylation modulation in pancreatic cancer
Authors: Zheng Shangyou , Tian Qing , Yuan Yuan , Sun Shuxin , Li Tingting , Xia Renpeng , He Rihua , Luo Yuming , Lin Qing , Fu Zhiqiang , Zhou Yu , Chen Rufu , Hu Chonghui
Published: November 2023

Background

Cancer-associated fibroblasts (CAFs) play pivotal roles in chemoresistance of pancreatic ductal adenocarcinoma (PDAC). However, the underlying mechanisms are poorly understood. Revealing the cross-talk network between tumor stroma and pancreatic cancer and developing effective strategies against oxaliplatin resistance are highly desired in the clinic.

Methods

High-throughput sequence was used to screened the key circRNAs transmitted by extracellular vesicles (EVs) from CAFs to pancreatic cancer cells. The associations between EV-packaged circBIRC6 and chemotherapy responsiveness were validated in a cohort of 82 cases of advanced PDAC patients. Then, the effects of EV-packaged circBIRC6 on CAF-induced oxaliplatin resistance were investigated by flow cytometry, colony formation, viability of pancreatic cancer organoids in vitro and by xenograft models in vivo. RNA pulldown, RNA immunoprecipitation, and sites mutation assays were used to reveal the underlying mechanism.

Results

We identified a circRNA, circBIRC6, is significantly upregulated in CAF-derived EVs and is positively associated with oxaliplatin-based chemoresistance. In vitro and in vivo functional assays showed that CAF-derived EV-packaged circBIRC6 enhance oxaliplatin resistance of pancreatic cancer cells and organoids via regulating the non-homologous end joining (NHEJ) dependent DNA repair. Mechanistically, circBIRC6 directly binds with XRCC4 and enhanced the interaction of XRCC4 with SUMO1 at the lysine 115 residue, which facilitated XRCC4 chromatin localization. XRCC4K115R mutation dramatically abrogated the EV-packaged circBIRC6 induced effect. Moreover, combination of antisense oligonucleotide inhibitors against circBIRC6 with Olaparib dramatically suppressed chemoresistance in patient-derived xenograft models.

Conclusions

Our study revealed that EV-packaged circBIRC6 confer oxaliplatin resistance in PDAC by mediating SUMOylation of XRCC4, introducing a promising predictive and therapeutic target for PDAC on oxaliplatin resistance.
Solubility of mesalazine in pseudo-binary mixtures of choline chloride/ethylene glycol deep eutectic solvent and water at 293.15 K to 313.15 K
Authors: Armani Elina , Jafari Parisa , Hemmati Salar , Rahimpour Elaheh , Barzegar-Jalali Mohammad , Jouyban Abolghasem
Published: November 2023

Mesalazine (5-ASA) is a medication utilized to treat inflammatory bowel diseases involving ulcerative colitis and Crohn’s disease. Mesalazine has fewer side effects but the low solubility and bioavailability of it is responsible for its delayed onset of action. Hence, the goal of this study is to determine the molar solubility of 5-ASA in aqueous pseudo-binary mixtures containing low toxic biocompatible choline chloride/ethylene glycol deep eutectic solvent (ChCl/EG DES) with DES mass fraction of 0.0–1.0 using a shake-flask technique at 293.2–313.2 K and approximately 85 kPa. The experimental results indicated that the solubility of 5-ASA enhanced by addition of DES mass fraction and also increasing temperature. The molarity values of 5-ASA were then modelled by some traditional cosolvency models, and regressed each model parameters. The back-computed molarity of 5-ASA using the selected cosolvency models presented a good consistency with the experimental data (lower mean percentage deviation than 5.14%). Moreover, the Gibbs and van’t Hoff equations were employed to compute the thermodynamic functions of 5-ASA dissolution process in ChCl/EG DES + water from the temperature dependency of solubility data. This analysis presented an endothermic and entropy-driven process of 5-ASA dissolution in ChCl/EG DES + water. Furthermore, enthalpy-entropy compensation analysis represented non-linear enthalpy dissolution vs. Gibbs free energy compensation plots with positive and negative slopes for 5-ASA whereas the positive and negative slopes were probably due to the enhance in solvation of 5-ASA by ChCl/EG DES molecules and the solvent-structure loosing, respectively.
Novel phenoxy-((phenylethynyl) selanyl) propan-2-ol derivatives as potential anticancer agents
Authors: Xu Wenxin , Du Yali , Pan Beibin , Wang Qiying , Zheng Haoran , Zhang Ruonan , Lou Jiaxin , Zhu Guanghui , Zhou Jie , Sun Jian
Published: November 2023

Selenocompounds protect against damage to healthy cells and induce the death of tumor cells by apoptosis; for this reason, they are attractive compounds for cancer research. In the present study, two series of novel phenoxy-((phenylethynyl) selanyl) propan-2-ol derivatives were synthesized, and their anti-proliferation activities were evaluated. Of the 23 compounds synthesized, most showed potent anti-proliferative activity against human cancer cell lines. Specifically, compounds 3h, 3g, and 3h-2, which had a 2- or 4-position halogen substituent on 1-((phenylethynyl)selanyl)-3-phenoxypropan-2-ol, exhibited the best anti-proliferative activity against tumor cells. Flow cytometry demonstrated that 3h, 3g, and 3h-2 induced G2/M phase arrest and apoptosis in A549 cells. Cellular studies demonstrated that the induction of apoptosis by 3h correlated with changes in the expression of cell cycle-related proteins and apoptosis-related proteins. Xenograft tumor experiments in nude mice revealed that compound 3h has antitumor effects in vivo and no evident toxic effects in nude mice. In addition, compound 3h alleviated cisplatin-induced liver and kidney damage. These findings uncover the applicability of compound 3h as a novel lead compound for cancer treatment.
Characterization of human placenta-derived exosome (pExo) as a potential osteoarthritis disease modifying therapeutic
Authors: Huang Chenfei , Zhao Yuechao , Lin Shengchen , Li Lin , Guo Xuan , Yumiseba Sebastian , Yang Jeng-dar , Hariri Robert , Ye Qian , He Shuyang , Kilcoyne Adrian
Published: November 2023

Objective

Human placenta-derived exosomes (pExo) were generated, characterized, and evaluated as a therapeutic candidate for the treatment of osteoarthritis (OA).

Methods

pExo was generated from full-term human placenta tissues by sequential centrifugation, purification, and sterile filtration. Upon analysis of particle size, cytokine composition, and exosome marker expression, pExo was further tested in cell-based assays to examine its effects on human chondrocytes. In vivo therapeutic efficacies were evaluated in a medial meniscal tear/medial collateral ligament tear (MCLT + MMT) rat model, in which animals received pExo injections intraarticularly and weight bearing tests during in-life stage while histopathology and immunohistochemistry were performed as terminal endpoints.

Results

pExo displayed typical particle size, expressed maker proteins of exosome, and contained proteins with pro-proliferative, pro-anabolic, anti-catabolic, or anti-inflammatory activities. In vitro, pExo promoted chondrocyte migration and proliferation dose-dependently, which may involve its activation of cell growth-related signaling pathways. Expression of inflammatory and catabolic genes induced in a cellular OA model was significantly suppressed by pExo. In the rat OA model, pExo alleviated pain burden, restored cartilage degeneration, and downregulated expressions of pro-inflammatory, catabolic, or apoptotic proteins in a dose-dependent manner.

Conclusions

Our study demonstrates that pExo has multiple potential therapeutic effects including symptom control and disease modifying characteristics. This may make it an attractive candidate for further development as an anti-OA therapeutic.
Moment inequalities for mixing long-span high-frequency data and strongly consistent estimation of OU integrated diffusion process
Authors: Yang Shanchao , Xie Jiaying , Luo Shuyi , Li Zhiyong , Yang Xin
Published: November 2023

Mixing is not much used in the high-frequency literature so far. However, mixing is a common weakly dependent property of continuous and discrete stochastic processes, such as Gaussian, Ornstein–Uhlenberck (OU), Vasicek, CIR, CKLS, logistic diffusion, generalized logistic diffusion, and double-well diffusion processes. So, long-span high-frequency data typically have weak dependence, and using mixing to study them is also an alternative approach. In this paper, we give some moment inequalities for long-span high-frequency data with ϕ-mixing, ρ-mixing, and α-mixing. These inequalities are effective tools for studying asymptotic properties. Applying these inequalities, we investigate the strong consistency of parameter estimation for the OU-integrated diffusion process. We also derive the mean square error of the estimation of the OU process and the optimal interval for the drift parameter estimator.
Effectiveness of tailored screening for multidrug-resistant organisms upon admission to an intensive care unit in the United Arab Emirates
Authors: Park Sungsoo , Kim Heesuk , Gatchalian Katrine K. , Oh Hyeyoung
Published: November 2023

Background

Multidrug-resistant organism (MDRO) screening may identify high-risk patients for MDRO infection and curb the spread of these resistant pathogens. However, the heterogeneous practices in MDRO screening and the diversity of MDRO risk factors necessitate a tailored approach for successful implementation. This study aimed to evaluate the performance of tailored MDRO screening in predicting MDRO carriage compared to universal screening.

Methods

Critically ill patients who underwent MDRO screening tests upon intensive care unit admission between September 2015 and December 2019 were included in the study. A risk-predicting model was developed using risk factors identified through multivariable logistic regression analysis. If an individual had one or more identified risk factors, the individual was deemed to be at risk of MDRO carriage and undergo tailored screening. The sensitivity of tailored screening was compared with universal screening for methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Gram-negative bacilli (carbapenem-resistant Acinetobacter baumannii and carbapenem-resistant Enterobacterales).

Results

The use of tracheostomy or endotracheal tubes, previous antibiotic exposure, previous multidrug-resistant Gram-negative bacilli carriage history, admission to the medical department, peripheral vascular disease, and liver disease were associated with positive screening for multidrug-resistant Gram-negative bacilli. These six risk factors accounted for all positive screening for multidrug-resistant Gram-negative bacilli, requiring 38.6% of all tests. Notably, MRSA had different risk factor profiles, and the risk factor-based screening approach detected only 43.1% (31 out of 72) of MRSA-positive cases.

Conclusions

Tailored screening based on identified risk factors showed variable sensitivities to individual MDROs compared to universal screening. A tailored screening approach for individual MDROs may enhance the overall effectiveness of MDRO screening programs.