bluuebunny/crossref_metadata_2025 huggingface dataset:
Health-based homophily in public housing developments
Authors: Heaton Brenda , Gondal Neha
Published: February 2023

Public housing residents in the United States face disproportionately high risks for disease, presenting an urgent need for interventions. Evidence suggests interventions leveraging social networks can be successful when relationships are homophilous, as this leads to pooling of risk behaviors among interconnected alters. Yet, we know little about networks of public housing residents. To assess the feasibility of network-based interventions, we investigate the incidence of health-based homophily in public housing developments in Boston, Massachusetts. Employing multilevel models (HLM), we find that respondents report their own health characteristics to be similar to their network partners on oral health, weight, and consumption of sugar-sweetened beverages and foods. We discuss the implications of our findings for health-based interventions in low-income communities.
Outcomes of endodontic microsurgery using different calcium silicate–based retrograde filling materials: a cohort retrospective cone-beam computed tomographic analysis
Authors: Eskandar Rawan F. , Al-Habib Mey A. , Barayan Mohammed A. , Edrees Hadeel Y.
Published: February 2023

Purpose

To evaluate the outcomes of endodontic microsurgery (EMS) using mineral trioxide aggregate (MTA; Dentsply Sirona, Charlotte, NC, USA), EndoSequence root repair material (RRM putty; Brasseler, Savannah, GA), and injectable Bioceramic (BC) sealer (Brasseler USA) followed by the application of RRM putty (lid technique) as root-end filling materials.

Methods

One hundred and ten patients who underwent EMS between 2016 and 2020 at King Abdulaziz University Dental Hospital were recruited for clinical and radiographic follow-up after a minimum of 1 year. Radiographic assessment was performed using periapical radiographs (PAs) and cone-beam computed tomography (CBCT). Volumetric analysis of periapical radiolucencies (PARLs) was performed using Amira software.

Results

Seventy-nine patients (103 teeth: MTA group, n = 28; RRM putty, n = 41; lid technique, n = 34), attended the follow-up visit, with an average follow-up period of 24 months (recall rate = 74.5%). Of the 103 teeth, 40 were anteriors, 24 were premolars, and 39 were molars. All three groups of retrograde filling materials (MTA, RRM putty, and lid technique) showed high success rates on both PA (85.7, 85.4, 94.1%, respectively) and CBCT imaging (67.9, 75.6, 88.2%, respectively), without any significant difference among the success rates of different materials. Overall, a slight agreement was noted between the PA and CBCT outcomes, with a statistically significant difference (P = 0.029). None of the patient-, tooth-, or treatment-related factors significantly influenced the outcomes of EMS. Adequate density of root canal filling material was significantly associated with a high percentage of completely healed cases on CBCT (P = 0.044). PARL volumes were reduced significantly over 1–4 years follow-up after EMS (P < 0.001)

Conclusions

EMS showed high success rates on both PA and CBCT when MTA, RRM putty or lid technique were used as retrograde filling materials. CBCT imaging is more precise than PA in detecting the healing outcomes of EMS.
Developing a model for rehabilitation in the home as hospital substitution for patients requiring reconditioning: a Delphi survey in Australia
Authors: Poulos Roslyn G , Cole Andrew M , Warner Kerry N , Faux Steven G , Nguyen Tuan-Anh , Kohler Friedbert , Un Fey-Ching , Alexander Tara , Capell Jacquelin T , Hilvert Dan R , O’Connor Claire MC , Poulos Christopher J
Published: February 2023

Background

Reconditioning for patients who have experienced functional decline following medical illness, surgery or treatment for cancer accounts for approximately 26% of all reported inpatient rehabilitation episodes in Australia. Rehabilitation in the home (RITH) has the potential to offer a cost-effective, high-quality alternative for appropriate patients, helping to reduce pressure on the acute care sector. This study sought to gain consensus on a model for RITH as hospital substitution for patients requiring reconditioning.

Methods

A multidisciplinary group of health professionals working in the rehabilitation field was identified from across Australia and invited to participate in a three-round online Delphi survey. Survey items followed the patient journey, and also included items on practitioner roles, clinical governance, and budgetary considerations. Survey items mostly comprised statements seeking agreement on 5-point Likert scales (strongly agree to strongly disagree). Free text boxes allowed participants to qualify item answers or make comments. Analysis of quantitative data used descriptive statistics; qualitative data informed question content in subsequent survey rounds or were used in understanding item responses.

Results

One-hundred and ninety-eight health professionals received an invitation to participate. Of these, 131/198 (66%) completed round 1, 101/131 (77%) completed round 2, and 78/101 (77%) completed round 3. Consensus (defined as ≥ 70% agreement or disagreement) was achieved on over 130 statements. These related to the RITH patient journey (including patient assessment and development of the care plan, case management and program provision, and patient and program outcomes); clinical governance and budgetary considerations; and included items for initial patient screening, patient eligibility and case manager roles. A consensus-based model for RITH was developed, comprising five key steps and the actions within each.

Conclusions

Strong support amongst survey participants was found for RITH as hospital substitution to be widely available for appropriate patients needing reconditioning. Supportive legislative and payment systems, mechanisms that allow for the integration of primary care, and appropriate clinical governance frameworks for RITH are required, if broad implementation is to be achieved. Studies comparing clinical outcomes and cost–benefit of RITH to inpatient rehabilitation for patients requiring reconditioning are also needed.
Evaluation of enhanced home care support clinics regarding emergency home visits, hospitalization, and end-of-life care: a retrospective cohort study in a city of Japan
Authors: Sun Yu , Iwagami Masao , Sakata Nobuo , Ito Tomoko , Inokuchi Ryota , Komiyama Jun , Kuroda Naoaki , Tamiya Nanako
Published: February 2023

Background

To meet the increasing demand for home healthcare in Japan as the population ages, home care support clinics/hospitals (HCSCs) and enhanced HCSCs were introduced in 2006 and 2012, respectively. This study aimed to evaluate whether enhanced HCSCs fulfilled the expected role in home healthcare.

Methods

We conducted a retrospective cohort study using linked medical and long-term care claims data from a municipality in Japan. Participants were ≥ 65 years of age, had newly started regular home visits between July 2014 and March 2018, and used either conventional or enhanced HCSCs. Patients were followed up for one year after they started regular home visits or until the month following the end of the regular home visits if they ended within one year. The outcome measures were (i) emergency home visits at all hours and on nights and holidays at least once, respectively, (ii) hospitalization at least once, and (iii) end-of-life care, which was evaluated based on the place of death and whether a physician was present at the time of in-home death. Multivariable logistic regression analyses were conducted for the outcomes of emergency home visits and hospitalizations.

Results

The analysis included 802 patients, including 405 patients in enhanced HCSCs and 397 patients in conventional HCSCs. Enhanced HCSCs had more emergency home visits at all hours than conventional HCSCs (65.7% vs. 49.1%; adjusted odds ratio 1.70, 95% CI [1.26–2.28]), more emergency home visits on nights and holidays (33.6% vs. 16.7%; 2.20 [1.55–3.13]), and fewer hospitalizations (21.5% vs. 32.2%; 0.55 [0.39–0.76]). During the follow-up period, 229 patients (152 patients in enhanced HCSCs and 77 patients in HCSCs) died. Deaths at home were significantly more common in enhanced HCSCs than in conventional HCSCs (80.9% vs. 64.9%; p < .001), and physician-attended deaths among those who died at home were also significantly more common in enhanced HCSCs (99.2% vs. 78.0%; p < .001).

Conclusions

This study confirms that enhanced HCSCs are more likely to be able to handle emergency home visits and end-of-life care at home, which are important medical functions in home healthcare. Further promotion of enhanced HCSCs would be advantageous.
Establishment and characterization of canine mammary tumoroids for translational research
Authors: Raffo-Romero Antonella , Aboulouard Soulaimane , Bouchaert Emmanuel , Rybicka Agata , Tierny Dominique , Hajjaji Nawale , Fournier Isabelle , Salzet Michel , Duhamel Marie
Published: February 2023

Background

Cancer heterogeneity is a main obstacle for the development of effective therapies, as its replication in in vitro preclinical models is challenging. Around 96% of developed drugs are estimated to fail from discovery to the clinical trial phase probably because of the unsuitability and unreliability of current preclinical models (Front Pharmacol 9:6, 2018; Nat Rev Cancer 8: 147–56, 2008) in replicating the overall biology of tumors, for instance the tumor microenvironment. Breast cancer is the most frequent cancer among women causing the greatest number of cancer-related deaths. Breast cancer can typically be modeled in vitro through the use of tumoroids; however, current approaches using mouse tumoroids fail to reproduce crucial aspect of human breast cancer, while access to human cells is limited and the focus of ethical concerns. New models of breast cancer, such as companion dogs, have emerged given the resemblance of developed spontaneous mammary tumors to human breast cancer in many clinical and molecular aspects; however, they have so far failed to replicate the tumor microenvironment. The present work aimed at developing a robust canine mammary tumor model in the form of tumoroids which recapitulate the tumor diversity and heterogeneity.

Results

We conducted a complete characterization of canine mammary tumoroids through histologic, molecular, and proteomic analysis, demonstrating their strong similarity to the primary tumor. We demonstrated that these tumoroids can be used as a drug screening model. In fact, we showed that paclitaxel, a human chemotherapeutic, could kill canine tumoroids with the same efficacy as human tumoroids with 0.1 to 1 μM of drug needed to kill 50% of the cells. Due to easy tissue availability, canine tumoroids can be produced at larger scale and cryopreserved to constitute a biobank. We have demonstrated that cryopreserved tumoroids keep the same histologic and molecular features (ER, PR, and HER2 expression) as fresh tumoroids. Furthermore, two cryopreservation techniques were compared from a proteomic point of view which showed that tumoroids made from frozen material allowed to maintain the same molecular diversity as from freshly dissociated tumor.

Conclusions

These findings revealed that canine mammary tumoroids can be easily generated and may provide an adequate and more reliable preclinical model to investigate tumorigenesis mechanisms and develop new treatments for both veterinary and human medicine.
Associations of the circulating levels of cytokines with risk of amyotrophic lateral sclerosis: a Mendelian randomization study
Authors: Liu Bin , Lyu Linshuoshuo , Zhou Wenkai , Song Jie , Ye Ding , Mao Yingying , Chen Guo-Bo , Sun Xiaohui
Published: February 2023

Background

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that is accompanied by muscle weakness and muscle atrophy, typically resulting in death within 3–5 years from the disease occurrence. Though the cause of ALS remains unclear, increasing evidence has suggested that inflammation is involved in the pathogenesis of ALS. Thus, we performed two-sample Mendelian randomization (MR) analyses to estimate the associations of circulating levels of cytokines and growth factors with the risk of ALS.

Methods

Genetic instrumental variables for circulating cytokines and growth factors were identified from a genome-wide association study (GWAS) of 8293 European participants. Summary statistics of ALS were obtained from a GWAS including 20,806 ALS cases and 59,804 controls of European ancestry. We used the inverse-variance weighted (IVW) method as the primary analysis. To test the robustness of our results, we further performed the simple-median method, weighted-median method, MR-Egger regression, and MR pleiotropy residual sum and outlier test. Finally, a reverse MR analysis was performed to assess the possibility of reverse causation between ALS and the cytokines that we identified.

Results

After Bonferroni correction, genetically predicted circulating level of basic fibroblast growth factor (FGF-basic) was suggestively associated with a lower risk of ALS [odds ratio (OR): 0.74, 95% confidence interval (95% CI): 0.60–0.92, P = 0.007]. We also observed suggestive evidence that interferon gamma-induced protein 10 (IP-10) was associated with a 10% higher risk of ALS (OR: 1.10, 95% CI: 1.03–1.17, P = 0.005) in the primary study. The results of sensitivity analyses were consistent.

Conclusions

Our systematic MR analyses provided suggestive evidence to support causal associations of circulating FGF-basic and IP-10 with the risk of ALS. More studies are warranted to explore how these cytokines may affect the development of ALS.
Leveraging innovation technologies to respond to malaria: a systematized literature review of emerging technologies
Authors: Chibi Moredreck , Wasswa William , Ngongoni Chipo , Baba Ebenezer , Kalu Akpaka
Published: February 2023

Background

In 2019, an estimated 409,000 people died of malaria and most of them were young children in sub-Saharan Africa. In a bid to combat malaria epidemics, several technological innovations that have contributed significantly to malaria response have been developed across the world. This paper presents a systematized review and identifies key technological innovations that have been developed worldwide targeting different areas of the malaria response, which include surveillance, microplanning, prevention, diagnosis and management.

Methods

A systematized literature review which involved a structured search of the malaria technological innovations followed by a quantitative and narrative description and synthesis of the innovations was carried out. The malaria technological innovations were electronically retrieved from scientific databases that include PubMed, Google Scholar, Scopus, IEEE and Science Direct. Additional innovations were found across grey sources such as the Google Play Store, Apple App Store and cooperate websites. This was done using keywords pertaining to different malaria response areas combined with the words “innovation or technology” in a search query. The search was conducted between July 2021 and December 2021. Drugs, vaccines, social programmes, and apps in non-English were excluded. The quality of technological innovations included was based on reported impact and an exclusion criterion set by the authors.

Results

Out of over 1000 malaria innovations and programmes, only 650 key malaria technological innovations were considered for further review. There were web-based innovations (34%), mobile-based applications (28%), diagnostic tools and devices (25%), and drone-based technologies (13%.

Discussion and conclusion

This study was undertaken to unveil impactful and contextually relevant malaria innovations that can be adapted in Africa. This was in response to the existing knowledge gap about the comprehensive technological landscape for malaria response. The paper provides information that countries and key malaria control stakeholders can leverage with regards to adopting some of these technologies as part of the malaria response in their respective countries.

The paper has also highlighted key drivers including infrastructural requirements to foster development and scaling up of innovations. In order to stimulate development of innovations in Africa, countries should prioritize investment in infrastructure for information and communication technologies and also drone technologies. These should be accompanied by the right policies and incentive frameworks.
Evidence for exposure dependent carriage of malaria parasites across the dry season: modelling analysis of longitudinal data
Authors: Stadler Eva , Cromer Deborah , Ogunlade Samson , Ongoiba Aissata , Doumbo Safiatou , Kayentao Kassoum , Traore Boubacar , Crompton Peter D. , Portugal Silvia , Davenport Miles P. , Khoury David S.
Published: February 2023

Background

In malaria endemic regions, transmission of Plasmodium falciparum parasites is often seasonal with very low transmission during the dry season and high transmission in the wet season. Parasites survive the dry season within some individuals who experience prolonged carriage of parasites and are thought to ‘seed’ infection in the next transmission season.

Methods

Dry season carriers and their role in the subsequent transmission season are characterized using a combination of mathematical simulations and data analysis of previously described data from a longitudinal study in Mali of individuals aged 3 months–12 years (n = 579).

Results

Simulating the life-history of individuals experiencing repeated exposure to infection predicts that dry season carriage is more likely in the oldest, most exposed and most immune individuals. This hypothesis is supported by the data from Mali, which shows that carriers are significantly older, experience a higher biting rate at the beginning of the transmission season and develop clinical malaria later than non-carriers. Further, since the most exposed individuals in a community are most likely to be dry season carriers, this is predicted to enable a more than twofold faster spread of parasites into the mosquito population at the start of the subsequent wet season.

Conclusions

Carriage of malaria parasites over the months-long dry season in Mali is most likely in the older, more exposed and more immune children. These children may act as super-spreaders facilitating the fast spread of parasites at the beginning of the next transmission season.
Risk assessment of cytologically indeterminate thyroid nodules with integrated molecular testing and repeat biopsy: a surgical decision-oriented tool
Authors: Guan Xuhuizi , Yu Tian , Zhang Zheng , Chen Lan , Yan An , Li Yao , Li Jiankun , Wang Dongdong , Sun Jie , Wang Feiliang , Miao Gang
Published: February 2023

Background

The preoperative diagnosis of cytologically indeterminate thyroid nodules (ITNs) is very challenging. In this study, we aim to provide an integrated risk assessment for thyroid nodules with indeterminate cytology to guide surgical decision-making, which includes results of blood tests, molecular tests, and repeat fine-needle aspiration biopsy (FNAB).

Methods

The study retrospectively included 265 ITNs between June 2019 and April 2022. According to our integrated risk assessment process that starts with blood testing, followed by supplementary DNA mutation detection on the first FNAB, and finally repeat FNAB, we divided the ITNs into high-risk and low-risk groups. Performance was evaluated with sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), area under the receiver operating characteristic curve (AUC), and the consistency between the risk evaluation and histological results.

Results

Of the 265 ITNs, 87 were included in the risk assessment process. The risk assessment had a sensitivity of 84.1%, specificity of 83.3%, PPV of 95.1%, NPV of 57.7%, and AUC of 0.837. The nodules with consistent results between the risk groups and histological outcomes, which included malignant cases in the high-risk group and benign cases in the low-risk group, accounted for 83.9% of all risk-assessed nodules.

Conclusions

These data suggest that the integrated risk assessment might provide proper information for surgical decision-making in patients with ITNs.
High anti-Müllerian hormone (AMH) is associated with increased risks of ectopic pregnancy in women undergoing fresh embryo transfer cycle, a cohort study
Authors: Hu Kai-Lun , Li Shan , Hunt Sarah , Yang Rui , Xu Huiyu , Li Rong
Published: February 2023

Background

Ectopic pregnancy is more common amongst assisted reproduction cycles and is a cause of significant maternal morbidity. Few predictive markers exist to help identify and modify risk of ectopic pregnancy in preparing for embryo transfer. The relationship between serum and AMH and ectopic pregnancy rate is unknown.

Methods

This was a retrospective cohort study investigating women who underwent fresh embryo transfer cycles from January 2017 to December 2019 in Peking University Third Hospital. The primary outcome was ectopic pregnancy. Restricted cubic splines with four knots for AMH concentration (0-3, 3-6, 6-12, 12-max) were used to map out the non-linear relationship between the predicted ectopic pregnancy rate and the serum AMH concentration. Log binomial regression was used to test the crude risk ratio (cRR) and the adjusted risk ratio (aRR) after adjustment for confounders with 95% confidence intervals (CI) to determine the difference across various groups.

Results

A total of 13,718 cycles in women undergoing fresh embryo transfer were eligible for analysis. The ectopic pregnancy rate was 1.3% per embryo transfer cycle initiated and 3.3% per pregnancy. Serum AMH concentrations were higher amongst women with ectopic pregnancy than in women with a confirmed intrauterine pregnancy or heterotopic pregnancy or who did not become pregnant (Mean levels: 4.0 ng/ml vs 3.2 ng/ml, 1.7 ng/ml, and 2.8 ng/ml). An AMH concentration of 7 ng/ml represented the best cut-off value to predict ectopic pregnancy. The ectopic pregnancy rate was 3.4% per cycle and 7.5% per pregnancy in women with AMH levels ≥ 7 ng/ml; and 1.2% per cycle and 2.9% per pregnancy in women with AMH levels < 7 ng/ml. Serum AMH concentration ≥ 7 ng/ml was associated with an increased risk of ectopic pregnancy in all fresh embryo transfer cycles started (aRR = 2.35 (1.45, 3.58)) as well in women who became pregnant (aRR = 2.23 (1.49, 3.33).

Conclusions

Baseline AMH concentration ≥ 7 ng/ml is associated with an increased risk of ectopic pregnancy in fresh embryo transfer cycles.
Influence of Vitamin D supplementation on reproductive outcomes of infertile patients: a systematic review and meta-analysis
Authors: Meng Xiangqian , Zhang Jiayao , Wan Qi , Huang Jihua , Han Tingting , Qu Ting , Yu Lin-lin
Published: February 2023

Background

Low vitamin D status has been associated with an increased risk for infertility. Recent evidence regarding the efficacy of vitamin D supplementation in improving reproductive outcomes is inconsistent. Therefore, this systematic review was conducted to investigate whether vitamin D supplementation could improve the reproductive outcomes of infertile patients and evaluate how the parameters of vitamin D supplementation affected the clinical pregnancy rate.

Methods

We searched seven electronic databases (CNKI, Cqvip, Wanfang, PubMed, Medline, Embase, and Cochrane Library) up to March 2022. Randomized and cohort studies were collected to assess the reproductive outcomes difference between the intervention (vitamin D) vs. the control (placebo or none). Mantel-Haenszel random effects models were used. Effects were reported as odds ratio (OR) and their 95% confidence interval (CI). PROSPERO database registration number: CRD42022304018.

Results

Twelve eligible studies (n = 2352) were included: 9 randomized controlled trials (RCTs, n = 1677) and 3 cohort studies (n = 675). Pooled results indicated that infertile women treated with vitamin D had a significantly increased clinical pregnancy rate compared with the control group (OR: 1.70, 95% CI: 1.24–2.34; I2 = 63%, P = 0.001). However, the implantation, biochemical pregnancy, miscarriage, and multiple pregnancy rates had no significant difference (OR: 1.86, 95% CI: 1.00–3.47; I2 = 85%, P = 0.05; OR: 1.49; 0.98–2.26; I2 = 63%, P = 0.06; OR: 0.98, 95% CI: 0.63–1.53; I2 = 0%, P = 0.94 and OR: 3.64, 95% CI: 0.58–11.98; I2 = 68%, P = 0.21). The improvement of clinical pregnancy rate in the intervention group was influenced by the vitamin D level of patients, drug type, the total vitamin D dosage, the duration, administration frequency, and daily dosage of vitamin D supplementation. The infertile women (vitamin D level < 30 ng/mL) treated with the multicomponent drugs including vitamin D (10,000–50,000 IU or 50,000–500,000 IU), or got vitamin D 1000–10,000 IU daily, lasting for 30–60 days could achieve better pregnancy outcome.

Conclusion

To the best of our knowledge, this is the first meta-analysis systematically investigated that moderate daily dosing of vitamin D supplementation could improve the clinical pregnancy rate of infertile women and reported the effects of vitamin D supplementation parameters on pregnancy outcomes. A larger sample size and high-quality RCTs are necessary to optimize the parameters of vitamin D supplementation to help more infertile patients benefit from this therapy.
Clinical impact of volume of disease and time of metastatic disease presentation on patients receiving enzalutamide or abiraterone acetate plus prednisone as first-line therapy for metastatic castration-resistant prostate cancer
Authors: Nuzzo Pier Vitale , Pederzoli Filippo , Saieva Calogero , Zanardi Elisa , Fotia Giuseppe , Malgeri Andrea , Rossetti Sabrina , Valenca Bueno Loana , Andrade Livia Maria Q. S. , Patrikidou Anna , Mestre Ricardo Pereira , Modesti Mikol , Pignata Sandro , Procopio Giuseppe , Fornarini Giuseppe , De Giorgi Ugo , Russo Antonio , Francini Edoardo ,   the SPARTACUSS Investigators
Published: February 2023

Background

Metastatic castration-resistant prostate cancer remains a challenging condition to treat. Among the available therapeutic options, the androgen receptor signaling inhibitors abiraterone acetate plus prednisone (AA) and enzalutamide (Enza), are currently the most used first-line therapies in clinical practice. However, validated clinical indicators of prognosis in this setting are still lacking. In this study, we aimed to evaluate a prognostic model based on the time of metastatic disease presentation (after prior local therapy [PLT] or de-novo [DN]) and disease burden (low volume [LV] or high-volume [HV]) at AA/Enza onset for mCRPC patients receiving either AA or Enza as first-line.

Methods

A cohort of consecutive patients who started AA or Enza as first-line treatment for mCRPC between January 1st, 2015, and April 1st, 2019 was identified from the clinical and electronic registries of the 9 American and European participating centers. Patients were classified into 4 cohorts by the time of metastatic disease presentation (PLT or DN) and volume of disease (LV or HV; per the E3805 trial, HV was defined as the presence of visceral metastases and/or at least 4 bone metastases of which at least 1 out the axial/pelvic skeleton) at AA/Enza onset. The endpoint was overall survival defined as the time from AA or Enza initiation, respectively, to death from any cause or censored at the last follow-up visit, whichever occurred first.

Results

Of the 417 eligible patients identified, 157 (37.6%) had LV/PLT, 87 (20.9%) LV/DN, 64 (15.3%) HV/PLT, and 109 (26.1%) HV/DN. LV cohorts showed improved median overall survival (59.0 months; 95% CI, 51.0–66.9 months) vs. HV cohorts (27.5 months; 95% CI, 22.8–32.2 months; P = 0.0001), regardless of the time of metastatic presentation. In multivariate analysis, HV cohorts were confirmed associated with worse prognosis compared to those with LV (HV/PLT, HR = 1.87; p = 0.029; HV/DN, HR = 2.19; P = 0.002).

Conclusion

Our analysis suggests that the volume of disease could be a prognostic factor for patients starting AA or Enza as first-line treatment for metastatic castration-resistant prostate cancer, pending prospective clinical trial validation.
Incorporating knowledge of disease-defining hub genes and regulatory network into a machine learning-based model for predicting treatment response in lupus nephritis after the first renal flare
Authors: Lee Ding-Jie , Tsai Ping-Huang , Chen Chien-Chou , Dai Yang-Hong
Published: February 2023

Background

Identifying candidates responsive to treatment is important in lupus nephritis (LN) at the renal flare (RF) because an effective treatment can lower the risk of progression to end-stage kidney disease. However, machine learning (ML)-based models that address this issue are lacking.

Methods

Transcriptomic profiles based on DNA microarray data were extracted from the GSE32591 and GSE112943 datasets. Comprehensive bioinformatics analyses were performed to identify disease-defining genes (DDGs). Peripheral blood samples (GSE81622, GSE99967, and GSE72326) were used to evaluate the effect of DDGs. Single-sample gene set enrichment analysis (ssGSEA) scores of the DDGs were calculated and correlated with specific immunology genes listed in the nCounter panel. GSE60681 and GSE69438 were used to examine the ability of the DDGs to discriminate LN from other renal diseases. K-means clustering was used to obtain the separate gene sets. The clustering results were extended to data derived using the nCounter technique. The least absolute shrinkage and selection operator (LASSO) algorithm was used to identify genes with high predictive value for treatment response after the first RF in each cluster. LASSO models with tenfold validation were built in GSE200306 and assessed by receiver operating characteristic (ROC) analysis with area under curve (AUC). The models were validated by using an independent dataset (GSE113342).

Results

Forty-five hub genes specific to LN were identified. Eight optimal disease-defining clusters (DDCs) were identified in this study. Th1 and Th2 cell differentiation pathway was significantly enriched in DDC-6. LCK in DDC-6, whose expression positively correlated with various subsets of T cell infiltrations, was found to be differentially expressed between responders and non-responders and was ranked high in regulatory network analysis. Based on DDC-6, the prediction model had the best performance (AUC: 0.75; 95% confidence interval: 0.44–1 in the testing set) and high precision (0.83), recall (0.71), and F1 score (0.77) in the validation dataset.

Conclusions

Our study demonstrates that incorporating knowledge of biological phenotypes into the ML model is feasible for evaluating treatment response after the first RF in LN. This knowledge-based incorporation improves the model's transparency and performance. In addition, LCK may serve as a biomarker for T-cell infiltration and a therapeutic target in LN.
Increased basolateral amygdala metabolic activity during flavor familiarization: an experimental study
Authors: Menchén-Márquez Sergio , Banqueri María , Gómez-Chacón Beatriz , Arias Jorge L. , Gallo Milagros
Published: February 2023

Background

Novel flavors elicit a cautious neophobic response which is attenuated as the flavor becomes familiar and safe. The attenuation of neophobia reveals the formation of a safe memory. Previous lesion studies in rats have reported that basolateral amygdala integrity is required for taste neophobia, but not neophobia to flavor, i.e., taste linked to an odorous component. Accordingly, immunohistochemical analyses show that novel tastes induced higher basolateral amygdala activity when compared to familiar ones. However, a different role of basolateral amygdala in flavor attenuation of neophobia is suggested by lesion studies using a vinegar solution. Studies assessing basolateral amygdala activity during flavor attenuation of neophobia are lacking. Thus, we quantified cytochrome oxidase as an index of basolateral amygdala activity along the first and second vinegar exposures in order to assess flavor neophobia and attenuation of neophobia.

Methods

We exposed adult male Wistar rats either once or twice to a 3% cider vinegar solution or water, and compared the basolateral amygdala, piriform cortex and caudate putamen brain metabolic activity using cytochrome c-oxidase histochemistry.

Results

We found increased flavor intake and cytochrome c-oxidase histochemistry activity during the second exposure in basolateral amygdala, but not in the piriform cortex and caudate/putamen.

Conclusions

The main finding of the study is that BLA metabolic activity was higher in the group exposed to a familiar vinegar solution than in the groups exposed to either water or a novel vinegar solution.
Toward a multi-level strategy to reduce stigma in global mental health: overview protocol of the Indigo Partnership to develop and test interventions in low- and middle-income countries
Authors: Gronholm Petra C. , Bakolis Ioannis , Cherian Anish V. , Davies Kelly , Evans-Lacko Sara , Girma Eshetu , Gurung Dristy , Hanlon Charlotte , Hanna Fahmy , Henderson Claire , Kohrt Brandon A. , Lempp Heidi , Li Jie , Loganathan Santosh , Maulik Pallab K. , Ma Ning , Ouali Uta , Romeo Renee , Rüsch Nicolas , Semrau Maya , Taylor Salisbury Tatiana , Votruba Nicole , Wahid Syed Shabab , Zhang Wufang , Thornicroft Graham
Published: February 2023

There is increasing attention to the impacts of stigma and discrimination related to mental health on quality of life and access to and quality of healthcare. Effective strategies for stigma reduction exist, but most evidence comes from high-income settings. Recent reviews of stigma research have identified gaps in the field, including limited cultural and contextual adaptation of interventions, a lack of contextual psychometric information on evaluation tools, and, most notably, a lack of multi-level strategies for stigma reduction. The Indigo Partnership research programme will address these knowledge gaps through a multi-country, multi-site collaboration for anti-stigma interventions in low- and middle-income countries (LMICs) (China, Ethiopia, India, Nepal, and Tunisia). The Indigo Partnership aims to: (1) carry out research to strengthen the understanding of mechanisms of stigma processes and reduce stigma and discrimination against people with mental health conditions in LMICs; and (2) establish a strong collaborative research consortium through the conduct of this programme. Specifically, the Indigo Partnership involves developing and pilot testing anti-stigma interventions at the community, primary care, and mental health specialist care levels, with a systematic approach to cultural and contextual adaptation across the sites. This work also involves transcultural translation and adaptation of stigma and discrimination measurement tools. The Indigo Partnership operates with the key principle of partnering with people with lived experience of mental health conditions for the development and implementation of the pilot interventions, as well as capacity building and cross-site learning to actively develop a more globally representative and equitable mental health research community. This work is envisioned to have a long-lasting impact, both in terms of the capacity building provided to participating institutions and researchers, and the foundation it provides for future research to extend the evidence base of what works to reduce and ultimately end stigma and discrimination in mental health.
Cancer aggravation due to persistent pain signals with the increased expression of pain-related mediators in sensory neurons of tumor-bearing mice
Authors: Tanaka Kenichi , Kondo Takashige , Narita Michiko , Muta Takeru , Yoshida Sara , Sato Daisuke , Suda Yukari , Hamada Yusuke , Shimizu Takatsune , Kuzumaki Naoko , Narita Minoru
Published: February 2023

A growing body of evidence suggests that intractable pain reduces both the quality of life and survival in cancer patients. In the present study, we evaluated whether chronic pain stimuli could directly affect cancer pathology using tumor-bearing mice. For this purpose, we used two different models of chronic pain in mice, neuropathic pain and persistent postsurgical pain, with Lewis lung carcinoma (LLC) as tumor cells. We found that tumor growth was dramatically promoted in these pain models. As well as these pain models, tumor growth of LLC, severe osteosarcoma (AXT) and B16 melanoma cells was significantly promoted by concomitant activation of sensory neurons in AAV6-hM3Dq-injected mice treated with the designer drug clozapine-N-oxide (CNO). Significant increases in mRNA levels of vascular endothelial growth factor-A (Vegfa), tachykinin precursor 1 (Tac1) and calcitonin-related polypeptide alpha (Calca) in the ipsilateral side of dorsal root ganglion of AAV6-hM3Dq-injected mice were observed by concomitant activation of sensory neurons due to CNO administration. Moreover, in a model of bone cancer pain in which mice were implanted with AXT cells into the right femoral bone marrow cavity, the survival period was significantly prolonged by repeated inhibition of sensory neurons of AAV6-hM4Di-injected mice by CNO administration. These findings suggest that persistent pain signals may promote tumor growth by the increased expression of sensory-located peptides and growth factors, and controlling cancer pain may prolong cancer survival.
Utilization of CT and MRI scanning in Taiwan, 2000–2017
Authors: Huang Chung-Chien , Effendi Fransisca Fortunata , Kosik Russell Oliver , Lee Wen-Jeng , Wang Li-Jen , Juan Chun-Jung , Chan Wing P.
Published: February 2023

Objectives

This population-based study aimed to collect, analyze, and summarize the long-term trends in medical imaging use in Taiwan.

Methods

A retrospective cohort population-based study of medical imaging usage for the individuals who received care under the National Health Insurance system from 2000 to 2017. CT and MRI utilization rates were determined overall as well as across certain variables including patient age, hospital type, health care type, hospital characteristics, and geographic area.

Results

Individuals registered in our health insurance system have received 21,766,745 CT scans and 7,520,088 MRI scans from 2000 to 2017. Annual growth rates for both imaging types were positive over that period, though growth rates have slowed in recent years. The growth rate for CT use was greatest (9–12%) between 2001 and 2004, dropped to 2% in 2005, then generally rose thereafter, reaching 3% in 2017. Similarly, MRI use growth peaked at 24% between 2001 and 2003, dropped to 4% in 2005, then increased in a fluctuating manner, reaching 2% in 2017.

Conclusion

Over the past 2 decades, CT and MRI use in Taiwan has increased sharply, especially in the oldest age group (≥ 60 years old), but growth rates have slowed in recent years. Increases in imaging use have corresponded with improved clinical outcomes, including greater life expectancy and reduced mortality rates, though further assessment is required to demonstrate a direct link with imaging. Nevertheless, the better clinical outcomes are also predisposed by the comprehensive care covered by the NHI system.
Generation of multilineage liver organoids with luminal vasculature and bile ducts from human pluripotent stem cells via modulation of Notch signaling
Authors: Kim Hyo Jin , Kim Gyeongmin , Chi Kyun Yoo , Kim Hyemin , Jang Yu Jin , Jo Seongyea , Lee Jihun , Lee Youngseok , Woo Dong-Hun , Han Choongseong , Kim Sang Kyum , Park Han-Jin , Kim Jong-Hoon
Published: February 2023

Background

The generation of liver organoids recapitulating parenchymal and non-parenchymal cell interplay is essential for the precise in vitro modeling of liver diseases. Although different types of multilineage liver organoids (mLOs) have been generated from human pluripotent stem cells (hPSCs), the assembly and concurrent differentiation of multiple cell types in individual mLOs remain a major challenge. Particularly, most studies focused on the vascularization of mLOs in host tissue after transplantation in vivo. However, relatively little information is available on the in vitro formation of luminal vasculature in mLOs themselves.

Methods

The mLOs with luminal blood vessels and bile ducts were generated by assembling hepatic endoderm, hepatic stellate cell-like cells (HscLCs), and endothelial cells derived entirely from hPSCs using 96-well ultra-low attachment plates. We analyzed the effect of HscLC incorporation and Notch signaling modulation on the formation of both bile ducts and vasculature in mLOs using immunofluorescence staining, qRT-PCR, ELISA, and live-perfusion imaging. The potential use of the mLOs in fibrosis modeling was evaluated by histological and gene expression analyses after treatment with pro-fibrotic cytokines.

Results

We found that hPSC-derived HscLCs are crucial for generating functional microvasculature in mLOs. HscLC incorporation and subsequent vascularization substantially reduced apoptotic cell death and promoted the survival and growth of mLOs with microvessels. In particular, precise modulation of Notch signaling during a specific time window in organoid differentiation was critical for generating both bile ducts and vasculature. Live-cell imaging, a series of confocal scans, and electron microscopy demonstrated that blood vessels were well distributed inside mLOs and had perfusable lumens in vitro. In addition, exposure of mLOs to pro-fibrotic cytokines induced early fibrosis-associated events, including upregulation of genes associated with fibrotic induction and endothelial cell activation (i.e., collagen I, α-SMA, and ICAM) together with destruction of tissue architecture and organoid shrinkage.

Conclusion

Our results demonstrate that mLOs can reproduce parenchymal and non-parenchymal cell interactions and suggest that their application can advance the precise modeling of liver diseases in vitro.
Porcine epidemic diarrhea virus activates PERK-ROS axis to benefit its replication in Vero E6 cells
Authors: Zhou Yingshan , Zhang Yuxin , Dong Wanyu , Gan Shiqi , Du Jing , Zhou Xingdong , Fang Weihuan , Wang Xiaodu , Song Houhui
Published: February 2023

Of the three branches of unfolded protein response (UPR) that were reportedly activated by porcine epidemic diarrhea virus (PEDV), PERK is recently shown to act as an upstream regulator of oxidative response of the cells. However, it remains unknown if and how PERK activation during PEDV infection would result in oxidative stress, and whether activation of PERK and its downstream molecules affect PEDV replication. Here, we demonstrate that infection with the PEDV strain YJH/2015 triggered UPR in Vero E6 cells by activating the PERK/eIF2α pathway and led to significant increase in the expression of proapoptotic protein C/EBP homologous protein (CHOP) and ER oxidoreductase 1 alpha (ERO1α). Inhibition of PERK by short hairpin RNA (shRNA) or GSK2606414 and knockdown of CHOP by small interfering RNA reduced expression of ERO1α and generation of ROS in PEDV-infected cells. Inhibition of ERO1α by shRNA or EN460 decreased PEDV-induced ROS generation. Genetic or pharmacological inhibition of each component of PERK, CHOP, ERO1α, and ROS led to significant suppression of PEDV replication. Collectively, our study provides the first evidence that PEDV manipulates endoplasmic reticulum to perturb its redox homeostasis via the PERK-CHOP-ERO1α-ROS axis in favor of its replication.
Over supplementation with vitamin B12 alters microbe-host interactions in the gut leading to accelerated Citrobacter rodentium colonization and pathogenesis in mice
Authors: Forgie Andrew J. , Pepin Deanna M. , Ju Tingting , Tollenaar Stephanie , Sergi Consolato M. , Gruenheid Samantha , Willing Benjamin P.
Published: February 2023

Background

Vitamin B12 supplements typically contain doses that far exceed the recommended daily amount, and high exposures are generally considered safe. Competitive and syntrophic interactions for B12 exist between microbes in the gut. Yet, to what extent excessive levels contribute to the activities of the gut microbiota remains unclear. The objective of this study was to evaluate the effect of B12 on microbial ecology using a B12 supplemented mouse model with Citrobacter rodentium, a mouse-specific pathogen. Mice were fed a standard chow diet and received either water or water supplemented with B12 (cyanocobalamin: ~120 μg/day), which equates to approximately 25 mg in humans. Infection severity was determined by body weight, pathogen load, and histopathologic scoring. Host biomarkers of inflammation were assessed in the colon before and after the pathogen challenge.

Results

Cyanocobalamin supplementation enhanced pathogen colonization at day 1 (P < 0.05) and day 3 (P < 0.01) postinfection. The impact of B12 on gut microbial communities, although minor, was distinct and attributed to the changes in the Lachnospiraceae populations and reduced alpha diversity. Cyanocobalamin treatment disrupted the activity of the low-abundance community members of the gut microbiota. It enhanced the amount of interleukin-12 p40 subunit protein (IL12/23p40; P < 0.001) and interleukin-17a (IL-17A; P < 0.05) in the colon of naïve mice. This immune phenotype was microbe dependent, and the response varied based on the baseline microbiota. The cecal metatranscriptome revealed that excessive cyanocobalamin decreased the expression of glucose utilizing genes by C. rodentium, a metabolic attribute previously associated with pathogen virulence.

Conclusions

Oral vitamin B12 supplementation promoted C. rodentium colonization in mice by altering the activities of the Lachnospiraceae populations in the gut. A lower abundance of select Lachnospiraceae species correlated to higher p40 subunit levels, while the detection of Parasutterella exacerbated inflammatory markers in the colon of naïve mice. The B12-induced change in gut ecology enhanced the ability of C. rodentium colonization by impacting key microbe-host interactions that help with pathogen exclusion. This research provides insight into how B12 impacts the gut microbiota and highlights potential consequences of disrupting microbial B12 competition/sharing through over-supplementation.

Graphical Abstract
Profile and outcomes of acute poisoning in the toxicology treatment and control center at Tanta University Hospital, Egypt
Authors: Rageh Omar El-Sayed , Sabra Hamdy Khaled , Alammar Abdulrahman Abdullah , Alanazi Omar Naif , Nagy Ayman , Kabbash Ibrahim Ali
Published: February 2023

Background

Poisoning is a major health problem especially in developing countries and leads to high morbidity and mortality.

Aim

To identify the profile of acute poisoning in the Toxicology Unit at Tanta University Hospital, Egypt (2017-2021).

Methods

A cross-sectional study using data extracted from medical records from beginning of January 2017 to end of December 2021. Data including demographic data, Glasgow coma scale, type of poisons, manner of poisoning, time of admission and discharge and state at discharge.

Results

This study included 9713 cases. Rodenticides represented the most frequent cause of poisoning among both males (30%) and females (27%). Pharmaceutical drugs, CNS abused pharmaceutical drugs, and chemicals represent the most common categories (24%, 22%, and 21%, respectively) among children (up to 12 years). Rodenticides and pharmaceutical drugs represent the highest categories among other age groups. Evening admissions represented 52% of cases. Glasgow coma scale was 15 among 86.3% of cases. Intentional poisoning was more common than accidental poisoning (58.6% and 34.7%, respectively). One half (52.2%) of the admitted cases were discharged within 24 hours of admission and 44.4% of them were discharged after 48-72 hours. Family request was the main reason of discharge of cases (70.3%), 15.7% were improved, 4% died. Mortality by rodenticide was 12.5%.

Conclusion

Rodenticides, pharmaceutical and CNS abused pharmaceutical drugs were the most common categories of poisoning. Intentional poisoning was more common than accidental poisoning. Rodenticides were responsible for most deaths.