bluuebunny/crossref_metadata_2025 huggingface dataset:
Morinda officinalis oligosaccharides mitigate depression-like behaviors in hypertension rats by regulating Mfn2-mediated mitophagy
Authors: Yang Lixuan , Ao Yutian , Li Yannan , Dai Baoan , Li Jingchun , Duan Wenzhe , Gao Wei , Zhao Zhonghui , Han Zhenyun , Guo Rongjuan
Published: February 2023

Objective

Patients with hypertension have a risk of depression. Morinda officinalis oligosaccharides (MOOs) have anti-depressant properties. In this study, we aimed to determine whether MOOs can improve the symptoms of depression in individuals with hypertension.

Methods

Dahl salt-sensitive rats fed with a high-salt diet were stimulated by chronic unpredictable mild stress to mimic hypertension with depression. Primary astrocytes and neurons were isolated from these rats. Astrocytes underwent LPS stimulation to simulate the inflammatory astrocytes during depression. MOOs were administrated at 0.1 mg/g/day in vivo and 1.25, 2.5, and 5 mg/mL in vitro. Mitophagy was inhibited using 5 mM 3-methyladenine (3-MA). Astrocyte-mediated neurotoxicity was detected by co-culturing astrocytes and neurons.

Results

MOOs decreased systolic pressure, diastolic pressure, and mean arterial pressure, thereby improving depression-like behavior, including behavioral despair, lack of enthusiasm, and loss of pleasure during hypertension with depression. Furthermore, MOOs inhibited inflammation, astrocytic dysfunction, and mitochondrial damage in the brain. Then, MOOs promoted autophagosome and lysosome enriched in mitochondria in LPS-stimulated astrocytes. MOOs suppressed mitochondrial damage and the release of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β in astrocytes undergoing LPS stimulation. Importantly, MOOs rescued the impaired neurons co-cultured with astrocytes. The effects of MOOs on LPS-stimulated astrocytes were reversed by 3-MA. Finally, MOOs upregulated LPS-downregulated Mfn2 expression in astrocytes. Mfn2 inhibition partly reversed the effects of MOOs on hypertension with depression. Intriguingly, Mfn2 suppression activated PI3K/Akt/mTOR pathway during MOOs treatment.

Conclusions

Astrocytes develop neuroinflammation in response to mitochondrial damage during hypertension with depression. MOOs upregulated Mfn2 expression to activate the PI3K/Akt/mTOR pathway-mediated mitophagy, thereby removing impaired mitochondria in astrocytes.

Highlights

MOOs have anti-hypertensive and anti-depressive properties.

MOOs inhibit inflammation and injury in astrocytes during hypertension with depression.

MOOs induce mitophagy activation in inflammatory astrocytes with mitochondrial damage.

MOOs upregulate Mfn2 expression in astrocytes.

Mfn2 activates mitophagy to resist mitochondrial damage in astrocytes.
Commentary: locating the restriction point
Authors: Brooks Robert F.
Published: February 2023

Attempts to map the Restriction Point in the mammalian cell cycle typically involve stimulating quiescent cells with mitogens for increasing intervals, removing the stimulus and then determining the proportion of cells that reach S phase at some point later. This “fixed point” estimate assumes that further cell cycle commitment ceases as soon as the stimulus is removed. In fact, kinetic analysis shows that the probability of cell cycle commitment does not fall back to its initial low value, immediately after a pulse of mitogens, but may instead remain slightly elevated for some while afterwards, compared to the starting quiescent population. Thus, cells entering S phase after a brief exposure to mitogens are not those that pass the Restriction Point early. Rather, they represent cells that continue on to S phase as a result of this residual, low probability of cell cycle commitment. Instead, the mitogen-regulated process(es) affecting the probability of cell cycle commitment are much closer to the start of S phase itself. Since the acquisition of (apparent) mitogen independence is such a poor indicator of the timing of cell cycle commitment, it is argued that a better measure is the point of insensitivity to CDK4,6 inhibitors such as palbociclib, which indicates when hyperphosphorylation of the Retinoblastoma Protein, RB, ceases to be dependent on mitogen-signalling pathways regulating CDK4,6/cyclin D activity.
De-Implementing Opioids for Dental Extractions (DIODE): a multi-clinic, cluster-randomized trial of clinical decision support strategies in dentistry
Authors: Gryczynski Jan , Mitchell Shannon Gwin , Asche Stephen E. , Truitt Anjali R. , Worley Donald C. , Rindal D. Brad
Published: February 2023

Background

Opioid pain relievers are commonly prescribed following dental extractions, but evidence shows that non-opioid analgesics often provide adequate pain relief with fewer risks. The current study examined clinical decision support (CDS) as a tool for de-implementing opioid prescribing in dentistry.

Methods

This prospective, cluster-randomized trial examined CDS for dental pain management at 22 HealthPartners Dental Group clinics in Minnesota. Dental providers (n = 49) were randomized to deliver care using CDS, CDS with patient education materials (CDS-E), or standard practice (SP). Randomization was stratified by provider type (dentist vs. oral surgeon) and baseline opioid prescribing volume. Patient records of dental extractions were examined for January 2019 through May 2021, representing a 12-month baseline and 15-month intervention period (N = 12,924). Opioid prescription at the visit (no vs. yes) was the primary outcome. Data were analyzed using generalized linear mixed models, adjusting for patient sex and age, extraction complexity, and baseline prescribing strata (volume and provider type).

Results

Patients were 56.2% female, with a mean age of 46.7 (SD = 20.0) years. Providers were 8% oral surgeons, 57% female, and with a mean age of 43.7 (SD = 11.2) years. There were significant decreases in opioid prescribing during the study (P < 0.001), representing a continuation of pre-existing trends to reduce opioid prescribing in these dental practices. There were no significant differences in opioid prescribing between CDS and SP (OR = 1.29; 97.5% CI = 0.93, 1.79; P = 0.08), or CDS-E and SP arms (OR = 1.27; 97.5% CI = 0.86, 1.79; P = 0.18). The direction of the association favored greater reductions in opioid prescribing in the SP arm. Despite training and implementation support, utilization of the CDS was low, particularly among oral surgeons, who were significantly more likely than other dentists to prescribe opioids. Among non-oral surgeon providers with the opportunity to access it, CDS utilization was not significantly associated with opioid prescribing.

Conclusions

Equipping dentists with CDS resources, whether alone or accompanied by patient education materials, did not accelerate reductions in opioid prescribing beyond those observed in standard practice. Strategies are needed to enhance CDS utilization for patient care and safety surrounding analgesia following dental extractions.

Trial registration

Clinicaltrials.gov, NCT03584789.
Estimating the prevalence of Epstein–Barr virus in primary gastric lymphoma: a systematic review and meta-analysis
Authors: Hirabayashi Mayo , Traverse-Glehen Alexandra , Combes Jean-Damien , Clifford Gary M. , de Martel Catherine
Published: February 2023

The stomach is a common site for extranodal non-Hodgkin’s lymphoma. While Helicobacter pylori (H. pylori) is the main established risk factor for primary gastric lymphoma, a fraction could be aetiologically associated with Epstein–Barr virus (EBV), a known haematolymphoid carcinogen. We systematically searched five databases from 1 January 1990 until 31 May 2022 for studies reporting EBV prevalence in gastric lymphoma tumour tissue by in-situ hybridisation (ISH) for EBV-encoded small RNA (PROSPERO CRD42020164473). We included representative series of more than five gastric lymphoma cases. Pooled prevalence and corresponding 95% confidence intervals (CI) of EBV in gastric tumour cells were calculated for two major gastric B-cell lymphoma types, mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B-cell lymphoma (DLBCL). When available, we also extracted data on H. pylori prevalence and survival by EBV status. We found ten studies including 194 cases of gastric MALT lymphoma and 11 studies including 643 cases of gastric DLBCL. EBV prevalence was 2.2% (95% CI: 0.5–13.3) in gastric MALT lymphoma and 11.0% (95% CI: 5.2–20.0) in gastric DLBCL. In a subset of studies, the prevalence of H. pylori was higher in gastric MALT lymphoma (51/69) compared to gastric DLBCL (62/102). Overall, our findings suggest that EBV is rarely seen in MALT lymphoma but is associated with around 10% of gastric DLBCL, similar to the proportion observed at other primary sites. EBV-related lymphoma adds a small number of cases to the burden of cancer that could be prevented by the future development of a vaccine against EBV.
Extracorporeal treatment for ethylene glycol poisoning: systematic review and recommendations from the EXTRIP workgroup
Authors: Ghannoum Marc , Gosselin Sophie , Hoffman Robert S. , Lavergne Valery , Mégarbane Bruno , Hassanian-Moghaddam Hossein , Rif Maria , Kallab Siba , Bird Steven , Wood David M. , Roberts Darren M. ,   for the EXTRIP Workgroup, Alhatali Badria , Anseeuw Kurt , Berling Ingrid , Bouchard Josée , Bunchman Timothy E. , Calello Diane P. , Chin Paul K. , Doi Kent , Galvao Tais , Goldfarb David S. , Hoegberg Lotte C. G. , Kebede Sofia , Kielstein Jan T. , Lewington Andrew , Li Yi , Macedo Etienne M. , MacLaren Rob , Mowry James B. , Nolin Thomas D. , Ostermann Marlies , Peng Ai , Roy Jean-Philippe , Shepherd Greene , Vijayan Anitha , Walsh Steven J. , Wong Anselm , Yates Christopher
Published: February 2023

Ethylene glycol (EG) is metabolized into glycolate and oxalate and may cause metabolic acidemia, neurotoxicity, acute kidney injury (AKI), and death. Historically, treatment of EG toxicity included supportive care, correction of acid–base disturbances and antidotes (ethanol or fomepizole), and extracorporeal treatments (ECTRs), such as hemodialysis. With the wider availability of fomepizole, the indications for ECTRs in EG poisoning are debated. We conducted systematic reviews of the literature following published EXTRIP methods to determine the utility of ECTRs in the management of EG toxicity. The quality of the evidence and the strength of recommendations, either strong (“we recommend”) or weak/conditional (“we suggest”), were graded according to the GRADE approach. A total of 226 articles met inclusion criteria. EG was assessed as dialyzable by intermittent hemodialysis (level of evidence = B) as was glycolate (Level of evidence = C). Clinical data were available for analysis on 446 patients, in whom overall mortality was 18.7%. In the subgroup of patients with a glycolate concentration ≤ 12 mmol/L (or anion gap ≤ 28 mmol/L), mortality was 3.6%; in this subgroup, outcomes in patients receiving ECTR were not better than in those who did not receive ECTR. The EXTRIP workgroup made the following recommendations for the use of ECTR in addition to supportive care over supportive care alone in the management of EG poisoning (very low quality of evidence for all recommendations): i) Suggest ECTR if fomepizole is used and EG concentration > 50 mmol/L OR osmol gap > 50; or ii) Recommend ECTR if ethanol is used and EG concentration > 50 mmol/L OR osmol gap > 50; or iii) Recommend ECTR if glycolate concentration is > 12 mmol/L or anion gap > 27 mmol/L; or iv) Suggest ECTR if glycolate concentration 8–12 mmol/L or anion gap 23–27 mmol/L; or v) Recommend ECTR if there are severe clinical features (coma, seizures, or AKI). In most settings, the workgroup recommends using intermittent hemodialysis over other ECTRs. If intermittent hemodialysis is not available, CKRT is recommended over other types of ECTR. Cessation of ECTR is recommended once the anion gap is < 18 mmol/L or suggested if EG concentration is < 4 mmol/L. The dosage of antidotes (fomepizole or ethanol) needs to be adjusted during ECTR.
Parity is associated with long-term differences in DNA methylation at genes related to neural plasticity in multiple sclerosis
Authors: Campagna Maria Pia , Xavier Alexandre , Stankovich Jim , Maltby Vicki E. , Slee Mark , Yeh Wei Z. , Kilpatrick Trevor , Scott Rodney J. , Butzkueven Helmut , Lechner-Scott Jeannette , Lea Rodney A. , Jokubaitis Vilija G.
Published: February 2023

Background

Pregnancy in women with multiple sclerosis (wwMS) is associated with a reduction of long-term disability progression. The mechanism that drives this effect is unknown, but converging evidence suggests a role for epigenetic mechanisms altering immune and/or central nervous system function. In this study, we aimed to identify whole blood and immune cell-specific DNA methylation patterns associated with parity in relapse-onset MS.

Results

We investigated the association between whole blood and immune cell-type-specific genome-wide methylation patterns and parity in 192 women with relapse-onset MS, matched for age and disease severity. The median time from last pregnancy to blood collection was 16.7 years (range = 1.5–44.4 years). We identified 2965 differentially methylated positions in whole blood, 68.5% of which were hypermethylated in parous women; together with two differentially methylated regions on Chromosomes 17 and 19 which mapped to TMC8 and ZNF577, respectively. Our findings validated 22 DMPs and 366 differentially methylated genes from existing literature on epigenetic changes associated with parity in wwMS. Differentially methylated genes in whole blood were enriched in neuronal structure and growth-related pathways. Immune cell-type-specific analysis using cell-type proportion estimates from statistical deconvolution of whole blood revealed further differential methylation in T cells specifically (four in CD4+ and eight in CD8+ T cells). We further identified reduced methylation age acceleration in parous women, demonstrating slower biological aging compared to nulligravida women.

Conclusion

Differential methylation at genes related to neural plasticity offers a potential molecular mechanism driving the long-term effect of pregnancy on MS outcomes. Our results point to a potential ‘CNS signature’ of methylation in peripheral immune cells, as previously described in relation to MS progression, induced by parity. As the first epigenome-wide association study of parity in wwMS reported, validation studies are needed to confirm our findings.
Evaluation of optimal monoenergetic images acquired by dual-energy CT in the diagnosis of T staging of thoracic esophageal cancer
Authors: Cheng Fanrong , Liu Yan , Du Lihong , Wang Lei , Li Lan , Shi Jinfang , Wang Xiaoxia , Zhang Jiuquan
Published: February 2023

Objectives

The purpose of our study was to objectively and subjectively assess optimal monoenergetic image (MEI (+)) characteristics from dual-energy CT (DECT) and the diagnostic performance for the T staging in patients with thoracic esophageal cancer (EC).

Methods

In this retrospective study, patients with histopathologically confirmed EC who underwent DECT from September 2019 to December 2020 were enrolled. One standard polyenergetic image (PEI) and five MEI (+) were reconstructed. Two readers independently assessed the lesion conspicuity subjectively and calculated the contrast-to-noise ratio (CNR) and the signal-to-noise ratio (SNR) of EC. Two readers independently assessed the T stage on the optimal MEI (+) and PEI subjectively. Multiple quantitative parameters were measured to assess the diagnostic performance to identify T1-2 from T3-4 in EC patients.

Results

The study included 68 patients. Subjectively, primary tumor delineation received the highest ratings in MEI (+) 40 keV of the venous phase. Objectively, MEI (+) images showed significantly higher SNR compared with PEI (p < 0.05), peaking at MEI (+) 40 keV in the venous phase. CNR of tumor (MEI (+) 40 keV -80 keV) was all significantly higher than PEI in arterial and venous phases (p < 0.05), peaking at MEI (+) 40 keV in venous phases. The agreement between MEI (+) 40 keV and pathologic T categories was 81.63% (40/49). Rho values in venous phases had excellent diagnostic efficiency for identifying T1-2 from T3-4 (AUC = 0.84).

Conclusions

MEI (+) reconstructions at low keV in the venous phase improved the assessment of lesion conspicuity and also have great potential for preoperative assessment of T staging in patients with EC.
Integrated analysis of RNA methylation regulators crosstalk and immune infiltration for predictive and personalized therapy of diabetic nephropathy
Authors: Li Jia , Liu Dongwei , Ren Jingjing , Li Guangpu , Zhao Zihao , Zhao Huanhuan , Yan Qianqian , Duan Jiayu , Liu Zhangsuo
Published: February 2023

Background

RNA methylation is a widely known post-transcriptional regulation which exists in many cancer and immune system diseases. However, the potential role and crosstalk of five types RNA methylation regulators in diabetic nephropathy (DN) and immune microenvironment remain unclear.

Methods

The mRNA expression of 37 RNA modification regulators and RNA modification regulators related genes were identified in 112 samples from 5 Gene Expression Omnibus datasets. Nonnegative Matrix Factorization clustering method was performed to determine RNA modification patterns. The ssGSEA algorithms and the expression of human leukocyte antigen were employed to assess the immune microenvironment characteristics. Risk model based on differentially expression genes responsible for the modification regulators was constructed to evaluate its predictive capability in DN patients. Furthermore, the results were validated by using immunofluorescence co-localizations and protein experiments in vitro.

Results

We found 24 RNA methylation regulators were significant differently expressed in glomeruli in DN group compared with control group. Four methylation-related genes and six RNA regulators were introduced into riskScore model using univariate Logistic regression and integrated LASSO regression, which could precisely distinguish the DN and healthy individuals. Group with high-risk score was associated with high immune infiltration. Three distinct RNA modification patterns were identified, which has significant differences in immune microenvironment, biological pathway and eGFR. Validation analyses showed the METTL3, ADAR1, DNMT1 were upregulated whereas YTHDC1 was downregulated in DN podocyte cell lines comparing with cells cultured by the normal glucose.

Conclusion

Our study reveals that RNA methylation regulators and immune infiltration regulation play critical roles in the pathogenesis of DN. The bioinformatic analyses combine with verification in vitro could provide robust evidence for identification of predictive RNA methylation regulators in DN.
Interleukin 6 and interferon gamma haplotypes are related to cytokine serum levels in dogs in an endemic Leishmania infantum region
Authors: Álvarez Luis , Marín-García Pablo-Jesús , Rentero-Garrido Pilar , Martinez-Jimenez Celia Pilar , Llobat Lola
Published: February 2023

Background

The Ibizan Hound is a canine breed native to the Mediterranean region, where leishmaniasis is an endemic zoonosis. Several studies indicate a low prevalence of this disease in Ibizan Hound dogs, whereas other canine breeds present a high prevalence. However, the underlying molecular mechanisms still remain unknown. The aim of this work is to analyse the relationship between serum levels of cytokines and the genomic profiles in two canine breeds, Ibizan Hound (resistant canine breed model) and Boxer (susceptible canine breed model).

Methods

In this study, we analyse the haplotypes of genes encoding cytokines related to immune response of Leishmania infantum infection in twenty-four Boxers and twenty-eight Ibizan Hounds apparently healthy using CanineHD DNA Analysis BeadChip including 165,480 mapped positions. The haplo.glm extension of haplo.score was used to perform a General Linear Model (GLM) regression to estimate the magnitude of individual haplotype effects within each cytokine.

Results

Mean levels of interferon gamma (IFN-γ), interleukin 2 (IL-2) and IL-18 in Boxer dogs were 0.19 ± 0.05 ng/ml, 46.70 ± 4.54 ng/ml, and 36.37 ± 30.59 pg/ml, whereas Ibizan Hound dogs present 0.49 ± 0.05 ng/ml, 64.55 ± 4.54 ng/ml, and 492.10 ± 31.18 pg/ml, respectively. The GLM regression shows fifteen haplotypes with statistically significant effect on the cytokine serum levels (P < 0.05). The more relevant are IL6-CGAAG and IFNG-GCA haplotypes, which increase and decrease the IL-2, IL-8 and IFN-γ serum levels, respectively.

Conclusions

Haplotypes in the IFNG and IL6 genes have been correlated to serum levels of IFN-γ, IL-2 and IL-18, and a moderate effect has been found on IL8 haplotype correlated to IL-8 and IL-18 serum levels. The results indicate that the resistance to L. infantum infection could be a consequence of certain haplotypes with a high frequency in the Ibizan Hound dog breed, while susceptibility to the disease would be related to other specific haplotypes, with high frequency in Boxer. Future studies are needed to elucidate whether these differences and haplotypes are related to different phenotypes in immune response and expression gene regulation to L. infantum infections in dogs and their possible application in new treatments and vaccines.

Graphical Abstract
Possible future scenarios of the general health social security system in Colombia for the year 2033
Authors: Aguilar Pedro Leon Cruz , Vásquez Javier Enrique Medina
Published: February 2023

This article formulates possible future scenarios for the Colombian General Health and Social Security System (GHSSS) in 2033 when it reaches its 40th anniversary. The research draws on intuitive logic from the School of Human and Social Foresight (Masini, Penser le futur, 2000). The approach considers that in contexts of high instability and high conflict of interests, a combination of methods is required for the analysis of relevant transformations. It entails applying methods based on evidence, expertise, interaction, and creativity as discussed by Keenan and Popper (Foresight 10:16–36, 2008). Three scenarios are devised with the participation of real actors representing a plurality of visions from the public, private, academic, and social sectors. Finally, two future scenarios are featured, the one chosen by the experts before the triumph of the current government and the one that the Ministry of Health will present to the Colombian Congress for approval in 2023.
Cross-lagged analysis of problematic social media use and phubbing among college students
Authors: Lv Shuai , Wang Hui
Published: February 2023

Background

Phubbing is a commonly seen phenomenon that has emerged in recent years among groups of college students, posing a rising challenge to educators. We conduct research in which the reciprocal relationship between problematic social media use and phubbing is explored and analysed quantitatively, aiming to discover reliable theoretical support to work out an appropriate intervention on students’ phubbing for students’ mental health concerns.

Methods

Using the problematic social media use scale and the phubbing scale, 328 college students from four universities in Shandong Province were enrolled in a two-stage longitudinal follow-up study for 20 months from December 2019 to August 2021. A cross-lagged model was constructed to explore the reciprocal relationship between problematic social media use and phubbing. The results of correlation analysis showed that problematic social media use was positively correlated with phubbing at both time points (r = 0.51, 0.53, P < 0.01).

Results

The results of cross-lagged regression analysis showed that the predictive effect of pretest problematic social media use on posttest problematic social media use was statistically significant (β = 0.24, P < 0.01). There was statistical significance in the prediction effect of pretest phubbing on posttest phubbing (β = 0.16, P < 0.05). Pretest problematic social media use had statistical significance in predicting posttest phubbing (β = 0.22, P < 0.01), and there was no statistical significance in the prediction of pretest phubbing on posttest problematic social media (β = 0.16, P < 0.05).

Conclusion

The problematic social media use of college students is closely related to phubbing, and problematic social media use can predict phubbing.
The sound of stress recovery: an exploratory study of self-selected music listening after stress
Authors: Adiasto Krisna , van Hooff Madelon L. M. , Beckers Debby G. J. , Geurts Sabine A. E.
Published: February 2023

Background

Empirical support for the notion that music listening is beneficial for stress recovery is inconclusive, potentially due to the methodological diversity with which the effects of music on stress recovery have been investigated. Little is presently known about which recovery activities are chosen by individuals for the purpose of stress recovery, and whether audio feature commonalities exist between different songs that are selected by individuals for the purpose of stress recovery. The current pre-registered study investigated whether audio feature commonalities can be extracted from self-selected songs for the purpose of stress recovery. Furthermore, the present study exploratorily examined the relationship between audio features and participants’ desired recovery-related emotions while listening and after listening to self-selected music.

Methods

Participants (N = 470) completed an online survey in which they described what music they would listen to unwind from a hypothetical stressful event. Data analysis was conducted using a split-sample procedure. A k-medoid cluster analysis was conducted to identify audio feature commonalities between self-selected songs. Multiple regression analyses were conducted to examine the relationship between audio features and desired recovery emotions.

Results

Participants valued music listening as a recovery activity to a similar extent as watching TV, sleeping, or talking to a significant other. Cluster analyses revealed that self-selected songs for the purpose of stress recovery can be grouped into two distinct categories. The two categories of songs shared similarities in key, loudness, speechiness, acousticness, instrumentalness, liveness, musical valence, tempo, duration, and time signature, and were distinguished by danceability, energy, and mode. No audio features were significantly associated with participants’ desired recovery emotions.

Conclusions

Although a comprehensive portrait of the relationship between audio features and stress recovery still warrants further research, the present study provides a starting point for future enquiries into the nuanced effects of musical audio features on stress recovery.
Psychological distress and associated factors among cancer patients in public hospitals, Addis Ababa, Ethiopia: a cross-sectional study
Authors: Negussie Frehiwot , Giru Berhanu Wordofa , Yusuf Nete Tewfik , Gela Debela
Published: February 2023

Background

Cancer has great implications for psychological, social, economic, and emotional dimensions. Psychological distress is overwhelming among cancer patients following a confirmed diagnosis. However, little is known about the prevalence of psychological distress and associated factors among cancer patients in Africa Sub-Saharan. Thus, this study aimed to assess the prevalence of psychological distress and associated factors among cancer patients in public hospitals in Addis Ababa, Ethiopia.

Methods

An institution-based cross-sectional study was conducted among cancer patients from September 15, 2019, to June 30, 2020. A total of 386 cancer patients selected through a simple random sampling technique participated in the study. Data were collected by an interview-administered questionnaire to evaluate psychological distress with a distress thermometer and social support with the Oslo 3-items Social Support Scale. The collected data were entered into Epi-data version 4.2 and exported into SPSS 25 for analysis, and then binary and multivariate logistic regressions were done to identify the association between dependent and independent variables.

Results

A total of 386 study participants were included in the study with a response rate of 91.4%. The prevalence of psychological distress among cancer patients in public hospitals in Addis Ababa, Ethiopia was 64.5%. Age > 45 years [AOR = 0.41; 95% CI (0.22–0.77)], marital status of being divorced [AOR = 3.3; 95%CI (1.23–8.71)] and married [AOR = 3.2; 95%CI (1.03–10.40)], rural residence [AOR = 1.5; 95%CI (1.15–5.18)], cancer stage II [AOR = 3.9; 95%CI (1.90–15.50)], stage III [AOR = 3.5;95%CI (1.45–8.44)] and stage IV [AOR = 3.4; 95%CI (1.90–10.11)], co-morbidity [AOR = 0.07; 95%CI: (0.03–0.17)], and moderate social support [AOR = 0.36; 95%CI (0.14–0.60)] and strong social support [AOR = 0.06; 95%CI (0.03–0.12)] were found to be significantly associated with psychological distress.

Conclusion

The prevalence of psychological distress among cancer patients in public hospitals in Addis Ababa, Ethiopia was high, and age, marital status, place of residence, cancer stage, co-morbidity, and social support were associated with psychological distress. Therefore, interventions focusing on these findings require special emphasis during designing interventions aimed at decreasing psychological distress.
Investigating coordinated account creation using burst detection and network analysis
Authors: Bellutta Daniele , Carley Kathleen M.
Published: February 2023

Democracies around the world face the threat of manipulation of their electorates via coordinated online influence campaigns. Researchers have responded by developing valuable methods for finding automated accounts and identifying false information, but these valiant efforts often fall into a cat-and-mouse game with perpetrators who constantly change their behavior. This has forced several researchers to go beyond the detection of individual malicious actors by instead identifying the coordinated activity that propels potent information operations. In this vein, we provide rigorous quantitative evidence for the notion that sudden increases in Twitter account creations may provide early warnings of online information operations. Analysis of fourteen months of tweets discussing the 2020 U.S. elections revealed that accounts created during bursts exhibited more similar behavior, showed more agreement on mail-in voting and mask wearing, and were more likely to be bots and share links to low-credibility sites. In concert with other techniques for detecting nefarious activity, social media platforms could temporarily limit the influence of accounts created during these bursts. Given the advantages of combining multiple anti-misinformation methods, we join others in presenting a case for the need to develop more integrable methods for countering online influence campaigns.
Nanomaterial-based biohybrid hydrogel in bioelectronics
Authors: Shin Minkyu , Lim Joungpyo , An Joohyun , Yoon Jinho , Choi Jeong-Woo
Published: February 2023

Despite the broadly applicable potential in the bioelectronics, organic/inorganic material-based bioelectronics have some limitations such as hard stiffness and low biocompatibility. To overcome these limitations, hydrogels capable of bridging the interface and connecting biological materials and electronics have been investigated for development of hydrogel bioelectronics. Although hydrogel bioelectronics have shown unique properties including flexibility and biocompatibility, there are still limitations in developing novel hydrogel bioelectronics using only hydrogels such as their low electrical conductivity and structural stability. As an alternative solution to address these issues, studies on the development of biohybrid hydrogels that incorporating nanomaterials into the hydrogels have been conducted for bioelectronic applications. Nanomaterials complement the shortcomings of hydrogels for bioelectronic applications, and provide new functionality in biohybrid hydrogel bioelectronics. In this review, we provide the recent studies on biohybrid hydrogels and their bioelectronic applications. Firstly, representative nanomaterials and hydrogels constituting biohybrid hydrogels are provided, and next, applications of biohybrid hydrogels in bioelectronics categorized in flexible/wearable bioelectronic devices, tissue engineering, and biorobotics are discussed with recent studies. In conclusion, we strongly believe that this review provides the latest knowledge and strategies on hydrogel bioelectronics through the combination of nanomaterials and hydrogels, and direction of future hydrogel bioelectronics.

Graphical Abstract
Trends and research foci of robotics-based STEM education: a systematic review from diverse angles based on the technology-based learning model
Authors: Darmawansah Darmawansah , Hwang Gwo-Jen , Chen Mei-Rong Alice , Liang Jia-Cing
Published: February 2023

Fostering students’ competence in applying interdisciplinary knowledge to solve problems has been recognized as an important and challenging issue globally. This is why STEM (Science, Technology, Engineering, Mathematics) education has been emphasized at all levels in schools. Meanwhile, the use of robotics has played an important role in STEM learning design. The purpose of this study was to fill a gap in the current review of research on Robotics-based STEM (R-STEM) education by systematically reviewing existing research in this area. This systematic review examined the role of robotics and research trends in STEM education. A total of 39 articles published between 2012 and 2021 were analyzed. The review indicated that R-STEM education studies were mostly conducted in the United States and mainly in K-12 schools. Learner and teacher perceptions were the most popular research focus in these studies which applied robots. LEGO was the most used tool to accomplish the learning objectives. In terms of application, Technology (programming) was the predominant robotics-based STEM discipline in the R-STEM studies. Moreover, project-based learning (PBL) was the most frequently employed learning strategy in robotics-related STEM research. In addition, STEM learning and transferable skills were the most popular educational goals when applying robotics. Based on the findings, several implications and recommendations to researchers and practitioners are proposed.
Single-time-point dosimetry using model selection and nonlinear mixed-effects modelling: a proof of concept
Authors: Hardiansyah Deni , Riana Ade , Beer Ambros J. , Glatting Gerhard
Published: February 2023

Purpose

This project aims to develop and evaluate a method for accurately determining time-integrated activities (TIAs) in single-time-point (STP) dosimetry for molecular radiotherapy. It performs a model selection (MS) within the framework of the nonlinear mixed-effects (NLME) model (MS–NLME).

Methods

Biokinetic data of [111In]In-DOTATATE activity in kidneys at T1 = (2.9 ± 0.6) h, T2 = (4.6 ± 0.4) h, T3 = (22.8 ± 1.6) h, T4 = (46.7 ± 1.7) h, and T5 = (70.9 ± 1.0) h post injection were obtained from eight patients using planar imaging. Eleven functions were derived from various parameterisations of mono-, bi-, and tri-exponential functions. The functions’ fixed and random effects parameters were fitted simultaneously (in the NLME framework) to the biokinetic data of all patients. The Akaike weights were used to select the fit function most supported by the data. The relative deviations (RD) and the root-mean-square error (RMSE) of the calculated TIAs for the STP dosimetry at T3 = (22.8 ± 1.6) h and T4 = (46.7 ± 1.7) h p.i. were determined for all functions passing the goodness-of-fit test.

Results

The function $$f_{4d} \left( t \right) = A_{1} /\left\{ {\left( {\frac{1 - \alpha }{{\lambda_{1} + \lambda_{{{\text{phys}}}} }}} \right) - \left( {\frac{\alpha }{{\lambda_{2} + \lambda_{{{\text{phys}}}} }}} \right) - \left( {\frac{1 - 2\alpha }{{\lambda_{bc} + \lambda_{{{\text{phys}}}} }}} \right)} \right\} \cdot e^{{ - \lambda_{{{\text{phys}}}} t}} \cdot \left\{ {\left( {1 - \alpha } \right) \cdot e^{{ - \lambda_{1} t}} - \alpha \cdot e^{{ - \lambda_{2} t}} - \left( {1 - 2\alpha } \right) \cdot e^{{ - \lambda_{bc} t}} } \right\}$$

f

4
d

t

=

A
1

/

1
-
α

λ
1

+

λ
phys

-

α

λ
2

+

λ
phys

-

1
-
2
α

λ

bc

+

λ
phys

·

e

-

λ
phys

t

·

1
-
α

·

e

-

λ
1

t

-
α
·

e

-

λ
2

t

-

1
-
2
α

·

e

-

λ

bc

t

with four adjustable parameters and $$\lambda_{bc} = \frac{{{\text{ln}}\left( 2 \right)}}{{1\;{\text{ min}}}}$$

λ

bc

=

ln

2

1

min

was selected as the function most supported by the data with an Akaike weight of (45 ± 6) %. RD and RMSE values show that the MS–NLME method performs better than functions with three or five adjustable parameters. The RMSEs of TIANLME–PBMS and TIA3-parameters were 7.8% and 10.9% (for STP at T3), and 4.9% and 10.7% (for STP at T4), respectively.

Conclusion

An MS–NLME method was developed to determine the best fit function for calculating TIAs in STP dosimetry for a given radiopharmaceutical, organ, and patient population. The proof of concept was demonstrated for biokinetic 111In-DOTATATE data, showing that four-parameter functions perform better than three- and five-parameter functions.
Distinguishing Killian–Jamieson diverticulum from Zenker’s diverticulum
Authors: Watanabe Yuki , Taniyama Yusuke , Koseki Ken , Ishida Hirotaka , Ozawa Yohei , Okamoto Hiroshi , Sato Chiaki , Unno Michiaki , Kamei Takashi
Published: February 2023

Background

Killian–Jamieson diverticulum, which is a relatively rare pharyngoesophageal diverticulum, is difficult to distinguish from Zenker’s diverticulum. Because major points of the relevant surgical procedures for these two entities differ, it is important to make an accurate diagnosis. We herein report a case of Killian–Jamieson diverticulum initially diagnosed as Zenker’s diverticulum.

Case presentation

A 56-year-old man complaining of discomfort during swallowing was diagnosed with pharyngoesophageal diverticulum. He was initially diagnosed with Zenker’s diverticulum before surgery, but the diverticulum actually arose from the left side of the esophageal wall, at the level of the cricoid cartilage and below the cricopharyngeal muscle. We therefore ultimately diagnosed this case as Killian–Jamieson diverticulum during surgery, and were able to preserve the muscle above the diverticulum, which would normally have to be cut when treating a case of Zenker’s diverticulum.

Conclusion

To make an accurate diagnosis, clinical and surgical findings are important to consider, including the location of the diverticulum and the relationship between the diverticula and cricopharyngeal muscles or between the diverticula, thyroid cartilage and cricoid cartilage.
Transmission sources and severe rat lung worm diseases in travelers: a scoping review
Authors: Meesing Atibordee , Khamsai Sittichai , Sawanyawisuth Kittisak , Tiamkao Somsak , Maleewong Wanchai , Limpawattana Panita , Sawunyavisuth Bundit , Ngamjarus Chetta , Boonsawat Watchara
Published: February 2023

Background

Rat lung worm disease (RLWD) has several clinical forms including eosinophilic meningitis (EOM) and two severe forms, eosinophilic meningoencephalitis (EOME) and eosinophilic radiculomyelitis (EORM). It remains unclear whether transmission sources are associated with severe forms of RLWD. This study aimed to evaluate if transmission factors are related to the severity of RLWD among travelers by using a scoping review of case reports.

Methods

This was a review using five databases to retrieve case reports and case series of travelers with RLWD. Clinical data and transmission sources of reported cases diagnosed as RLWD were retrieved. The outcome of the study was occurrence of severe forms of RLWD defined as EOME, EORM, and combined EOME/EORM.

Results

We retrieved 1,326 articles from five databases and 31 articles were included in the analysis. There were 84 cases eligible from 15 countries. Four cases were excluded. Seventy cases were in EOM group and 10 cases had EOME or EORM. Compared with the EOM group, the EOME, EORM, and combination EOME/EORM group had similar age, sex, and risk factors of consumptions of apple snails, shrimp and prawn, and salad/vegetables. The EOME group had higher proportion of consumption of African snails than the EOM group (60% vs 13.8%). However, only one study reported the consumption of African snails and the heterogeneity between studies and the small sample size impeded direct comparisons between groups.

Conclusions

RLWD in travelers can be found in most continents and mostly get infected from endemic countries of RLWD. Further studies are required to evaluate the association between transmission vectors and severity of RLWD.
Did weekly economic index and volatility index impact US food sales during the first year of the pandemic?
Authors: Das Narasingha , Gangopadhyay Partha
Published: February 2023

We explore the impacts of economic and financial dislocations caused by COVID-19 pandemic shocks on food sales in the United States from January 2020 to January 2021. We use the US weekly economic index (WEI) to measure economic dislocations and the Chicago Board Options Exchange volatility index (VIX) to capture the broader stock market dislocations. We validate the NARDL model by testing a battery of models using the autoregressive distributed lags (ARDL) methodology (ARDL, NARDL, and QARDL specifications). Our study postulates that an increase in WEI has a significant negative long-term effect on food sales, whereas a decrease in WEI has no statistically significant (long-run) effect. Thus, policy responses that ignore asymmetric effects and hidden cointegration may fail to promote food security during pandemics.
Association of tobacco use with the tobacco-related built environment: an ecological study from urban slums of Bhopal, India
Authors: Sabde Yogesh Damodar , Yadav Vikas , Pakhare Abhijit P. , Kumar Sanjeev , Joshi Ankur , Joshi Rajnish
Published: February 2023

Introduction

Tobacco is one of the biggest public health problems and a major risk factor for various non-communicable diseases (NCDs). An important aspect of tobacco control strategy could include modifications in the tobacco-related built environment. This study investigated the association between tobacco shop density and tobacco use prevalence in the urban slums of Bhopal city, India.

Methods

We conducted a cross-sectional survey to obtain the distribution of tobacco-related built environment (tobacco shops) in the neighbourhood (400-m service area) of 32 urban slum clusters of Bhopal. We plotted this distribution using the 'network service area analysis' in ArcMap 10.7.1 software. Then, we used an ecological design to determine the association between tobacco shop density and tobacco use prevalence in these 32 clusters (N = 6214 adult inhabitants). We used multiple linear regression analysis to estimate the regression coefficient (adjusted for socio-demographic variables) between tobacco use and tobacco shop density at the cluster level.

Results

The prevalence of tobacco use among all 32 slum clusters ranged from 22.1 to 59.6% (median 40.9% with IQR 31.8–44.2). There were 194 tobacco shops situated in the neighbourhood of all clusters. The median density of tobacco shops was 59.40/km2 (IQR 39.9–108.1/km2) in the neighbourhoods of slum clusters. Tobacco use prevalence was significantly associated with tobacco shop density (estimate or B = 0.071, p value = 0.002) after adjusting for age, literacy, wealth index, and gender ratio.

Conclusions

Tobacco use prevalence is significantly associated with tobacco shop density in the slums of Bhopal city in central India. We need to develop appropriate built environment interventions to control rampant tobacco use.
ANCHOR CRC: Results From a Single-Arm, Phase II Study of Encorafenib Plus Binimetinib and Cetuximab in Previously Untreated BRAFV600E-Mutant Metastatic Colorectal Cancer
Authors: Van Cutsem Eric , Taieb Julien , Yaeger Rona , Yoshino Takayuki , Grothey Axel , Maiello Evaristo , Elez Elena , Dekervel Jeroen , Ross Paul , Ruiz-Casado Ana , Graham Janet , Kato Takeshi , Ruffinelli Jose C. , André Thierry , Carrière Roussel Edith , Klauck Isabelle , Groc Mélanie , Vedovato Jean-Claude , Tabernero Josep
Published: February 2023

PURPOSE

The positive BEACON colorectal cancer (CRC) safety lead-in, evaluating encorafenib + cetuximab + binimetinib in previously treated patients with BRAFV600E-mutated metastatic CRC (mCRC), prompted the design of the phase II ANCHOR CRC study (ClinicalTrails.gov identifier: NCT03693170 ). ANCHOR CRC aimed to evaluate efficacy, safety, and quality of life with first-line encorafenib + binimetinib + cetuximab in BRAFV600E-mutated mCRC.

METHODS

In this multicenter, open-label, single-arm study, patients with BRAFV600E-mutated mCRC received oral encorafenib 300 mg once daily and binimetinib 45 mg twice daily in 28-day cycles, plus intravenous cetuximab 400 mg/m2 once on day 1 of cycle 1, then 250 mg/m2 once weekly for the first seven cycles, and 500 mg/m2 once on Days 1 and 15 from cycle 8 onward. The primary end point was locally assessed confirmed objective response rate (cORR), and secondary end points included centrally assessed cORR, progression-free survival, overall survival (OS), quality of life, and safety and tolerability.

RESULTS

Among 95 patients, the locally assessed cORR was 47.4% (95% CI, 37.0 to 57.9) with all partial responses. Since the lower limit of the 95% CI exceeded 30%, the primary end point was met. With a median follow-up duration of 20.1 months, the median progression-free survival on the basis of local assessments was 5.8 months and the median OS was 18.3 months. Treatment was well tolerated, with no unexpected toxicities. Using Patient Global Impression of Changes, substantial improvement in symptoms was consistently reported in ≥ 30% of patients from cycle 3 to cycle 10.

CONCLUSION

The ANCHOR CRC study showed that the scientifically driven combination of encorafenib + binimetinib + cetuximab was active in the first-line setting of BRAFV600E-mutated mCRC with a manageable safety profile. Further first-line evaluation is ongoing (ClinicalTrails.gov identifier: NCT04607421 ).
Microglia refine developing retinal astrocytic and vascular networks through the complement C3/C3aR axis
Authors: Gnanaguru Gopalan , Tabor Steven J. , Bonilla Gracia M. , Sadreyev Ruslan , Yuda Kentaro , Köhl Jörg , Connor Kip M.
Published: February 2023

Microglia, a resident immune cell of the central nervous system (CNS), play a pivotal role in facilitating neurovascular development through mechanisms that are not fully understood. Previous reports indicate a role for microglia in regulating astrocyte density. This current work resolves the mechanism through which microglia facilitate astrocyte spatial patterning and superficial vascular bed formation in the neuroretina during development. Ablation of microglia increased astrocyte density and altered spatial patterning. Mechanistically, we show that microglia regulate the formation of the spatially organized astrocyte template required for subsequent vascular growth, through the complement C3/C3aR axis during neuroretinal development. Lack of C3 or C3aR hindered the developmental phagocytic removal of astrocyte bodies and resulted in increased astrocyte density. In addition, increased astrocyte density was associated with elevated proangiogenic extracellular matrix gene expression in C3- and C3aR-deficient retinas, resulting in increased vascular density. These data demonstrate that microglia regulate developmental astrocyte and vascular network spatial patterning in the neuroretina via the complement axis.