bluuebunny/crossref_metadata_2025 huggingface dataset:
Protective effect of Cordyceps sinensis against diabetic kidney disease through promoting proliferation and inhibiting apoptosis of renal proximal tubular cells
Authors: Zhang Yuhan , Xu Lusi , Lu Yiran , Zhang Jing , Yang Mengge , Tian Yutian , Dong Jianjun , Liao Lin
Published: April 2023

Background

Diabetic kidney disease (DKD) has mainly been considered as a glomerular disease. Our previous study showed that the progression of DKD was highly correlated with the dysfunction of renal proximal tubular cells. Fermented Cordyceps sinensis (CS), a substitute for natural CS, is a prominent herb widely used in China, and has exhibited excellent efficacy on DKD. However, the underlying mechanisms remain poorly understood.

Methods

The database analysis was used to identify the main therapeutic targets and pathways of CS involved in DKD treatment. Next, the protective effects of fermented CS on high glucose (HG, 30 mM) induced HK-2 cell injury was validated through cell proliferation and apoptosis assay, including CCK-8, EdU and TUNEL. Finally, quantitative real‑time PCR (qRT-PCR) and western blotting were used to verify key target genes.

Results

Our results revealed that 9 main targets (RELA, JNK1, PTEN, VEGFA, EGF, ERK2, CASP3, AKT1, MMP9) were recognized as key therapeutic targets with excellent binding affinity screened by database analysis and molecular docking. The biological processes were identified by Gene Ontology (GO) enrichment, which appeared mainly involved in the positive regulation of cell proliferation as well as the negative regulation of apoptosis. The verification experiments in vitro revealed that fermented CS significantly attenuated the HG-induced cytotoxicity and apoptosis, and promoted the proliferation of HK-2 cells. Moreover, fermented CS significantly downregulated the expressions of Bax, Caspase-3, VEGFA, P-AKT and P-ERK, and upregulated the expression of PTEN compared with that of HG group.

Conclusion

Our results demonstrate that the fermented CS has nephroprotective effects significantly, which functions via promoting proliferation and inhibiting apoptosis of renal proximal tubular cells, likely by targeting Caspase-3, Bax, VEGFA and PTEN. Furthermore, AKT and ERK signaling pathway may be the critical mechanisms underlying the efficacy of fermented CS in DKD treatment.
Integrating social determinants of health principles into the preclinical medical curriculum via student-led pedagogical modalities
Authors: Kneer Krisandra , Zhang Erik , Harkness Tyler , Lahey Timothy , Lounsbury Karen M.
Published: April 2023

Background

Dismantling structural inequities in health care requires that physicians understand the impacts of social determinants of health (SDH). Although many medical schools incorporate SDH education, integration of these principles into the preclinical curriculum remains challenging.

Methods

Students and faculty at the University of Vermont, Larner College of Medicine developed the Social Medicine Theme of the Week (SMTW), a peer-teaching approach to integrating SDH topics across the preclinical curriculum as part of a broader social medicine curriculum. Students created objectives to link SDH-related topics to the weekly curriculum and presented them to the class. Student innovation led to the incorporation of creative online infographics that were published in the curriculum calendar. First year medical students and faculty members were surveyed to assess preferences and educational impact of the SMTW announcements with accompanying infographics.

Results

Of the 40 student respondents, 77.5% reported that their knowledge of SDH had improved due to the SMTW. Most students (82.5%) preferred the infographic modality over traditional teaching modalities. Faculty respondents reported limited engagement with the SMTW and, although they supported the need for these objectives, many (61%) found it difficult to integrate SDH content into their class materials.

Conclusion

Student-led infographics are a popular method of integrating SDH content in the preclinical curriculum that can be optimized through faculty orientation and support. Success for this type of instruction requires opportunities for student developers, integration and formal assessment of objectives, faculty engagement and training, and institutional support for creating and delivering a robust social medicine curriculum.
Dietary behaviors and attitudes among Norwegian medical students
Authors: Sanne Ingebjørg , Bjørke-Monsen Anne-Lise
Published: April 2023

Background

Dietary patterns and beliefs are influenced by socioeconomic status, cultural influences, as well as medical advice, social media and marketing. Medical doctors are expected to provide correct, updated and non-biased nutritional advice to their patients, but their own dietary behaviors and attitudes may influence nutritional counselling.

Methods

We have investigated dietary habits and food attitudes among medical students by using an anonymous survey distributed to all students at the Medical Faculty, University of Bergen, Norway. The survey included a 36-item questionnaire covering information about demographics, former and current diet, use of nutritional supplements, tobacco and alcohol, in addition to food attitudes and nutritional knowledge. Descriptive statistics were calculated for each survey item.

Results

Of the 880 students, 394 responded to the survey. Although 90% of the students were omnivores, the majority had a negative attitude towards meat, and considered fish to be healthier than meat. Significantly more women than men reported use of a special diet and excluded meat from their diet, even if they were omnivores. The most frequently used supplement was cod liver oil or omega 3 fatty acids.

Conclusion

The medical students’ diet and food attitudes not only reflect current health recommendations, but also popular beliefs and marketing in Norway. Curriculum planners should make the students capable of recognizing the influence of social media, marketing and medicine-food industry interactions, to ensure relevant nutrition knowledge for future doctors.
Physician-reported characteristics, representations, and ethical justifications of shared decision-making practices in the care of paediatric patients with prolonged disorders of consciousness
Authors: Sellaiah Vinurshia , Merlo Federica , Malacrida Roberto , Albanese Emiliano , Fadda Marta
Published: April 2023

Background

Despite consensus about the importance of implementing shared decision-making (SDM) in clinical practice, this ideal is inconsistently enacted today. Evidence shows that SDM practices differ in the degree of involvement of patients or family members, or in the amount of medical information disclosed to patients in order to “share” meaningfully in treatment decisions. Little is known on which representations and moral justifications physicians hold when realizing SDM. This study explored physicians’ experiences of SDM in the management of paediatric patients with prolonged disorders of consciousness (PDOC). Specifically, we focused on physicians’ SDM approaches, representations, and ethical justifications for engaging in SDM.

Methods

We used a qualitative approach to explore the SDM experiences of 13 ICU physicians, paediatricians, and neurologists based in Switzerland who have been or were involved in the care of paediatric patients living with PDOC. A semi-structured interview format was used and interviews were audio-recorded and transcribed. Data were analysed through thematic analysis.

Results

We found that participants followed three main decision-making approaches: the “brakes” approach, characterized by maximized family’s decisional freedom, though conditional to physician’s judgment regarding the medical appropriateness of a treatment; the “orchestra director” approach, characterized by a multi-step decision-making process led by the main physician aimed at eliciting the voices of the care team members and of the family; and the “sunbeams” approach, characterized by a process oriented to reach consensus with family members through dialogue, where the virtues of the physician are key to guide the process. We also found that participants differed in the moral justifications sustaining each approach, citing the duty to respect parental autonomy, to invest in an ethics of care, and to employ physicians’ virtues to guide the decision-making process.

Conclusion

Our results show that physicians come to perform SDM in different ways, with several representations, and distinct ethical justifications. SDM training among health care providers should clarify the ductility of SDM and the several ethical motivations underpinning it, rather than insisting on the principle of respect for patient’s autonomy as its only moral foundation.
Prediction of inappropriate pre-hospital transfer of patients with suspected cardiovascular emergency diseases using machine learning: a retrospective observational study
Authors: Kim Ji Hoon , Kim Bomgyeol , Kim Min Joung , Hyun Heejung , Kim Hyeon Chang , Chang Hyuk-Jae
Published: April 2023

Background

This study aimed to develop a prediction model for transferring patients to an inappropriate hospital for suspected cardiovascular emergency diseases at the pre-hospital stage, using variables obtained from an integrated nationwide dataset, and to assess the performance of this model.

Methods

We integrated three nationwide datasets and developed a two-step prediction model utilizing a machine learning algorithm. Ninety-eight clinical characteristics of patients identified at the pre-hospital stage and 13 hospital components were used as input data for the model. The primary endpoint of the model was the prediction of transfer to an inappropriate hospital.

Results

A total of 94,256 transferred patients in the public pre-hospital care system matched the National Emergency Department Information System data of patients with a pre-hospital cardiovascular registry created in South Korea between July 2017 and December 2018. Of these, 1,770 (6.26%) patients failed to be transferred to a capable hospital. The area under the receiver operating characteristic curve of the final predictive model was 0.813 (0.800–0.825), and the area under the receiver precision-recall curve was 0.286 (0.265–0.308).

Conclusions

Our prediction model used machine learning to show favorable performance in transferring patients with suspected cardiovascular disease to a capable hospital. For our results to lead to changes in the pre-hospital care system, a digital platform for sharing real-time information should be developed.
Optimizing prognostic factors of five-year survival in gastric cancer patients using feature selection techniques with machine learning algorithms: a comparative study
Authors: Afrash Mohammad Reza , Mirbagheri Esmat , Mashoufi Mehrnaz , Kazemi-Arpanahi Hadi
Published: April 2023

Background

Gastric cancer is the most common malignant tumor worldwide and a leading cause of cancer deaths. This neoplasm has a poor prognosis and heterogeneous outcomes. Survivability prediction may help select the best treatment plan based on an individual’s prognosis. Numerous clinical and pathological features are generally used in predicting gastric cancer survival, and their influence on the survival of this cancer has not been fully elucidated. Moreover, the five-year survivability prognosis performances of feature selection methods with machine learning (ML) classifiers for gastric cancer have not been fully benchmarked. Therefore, we adopted several well-known feature selection methods and ML classifiers together to determine the best-paired feature selection-classifier for this purpose.

Methods

This was a retrospective study on a dataset of 974 patients diagnosed with gastric cancer in the Ayatollah Talleghani Hospital, Abadan, Iran. First, four feature selection algorithms, including Relief, Boruta, least absolute shrinkage and selection operator (LASSO), and minimum redundancy maximum relevance (mRMR) were used to select a set of relevant features that are very informative for five-year survival prediction in gastric cancer patients. Then, each feature set was fed to three classifiers: XG Boost (XGB), hist gradient boosting (HGB), and support vector machine (SVM) to develop predictive models. Finally, paired feature selection-classifier methods were evaluated to select the best-paired method using the area under the curve (AUC), accuracy, sensitivity, specificity, and f1-score metrics.

Results

The LASSO feature selection algorithm combined with the XG Boost classifier achieved an accuracy of 89.10%, a specificity of 87.15%, a sensitivity of 89.42%, an AUC of 89.37%, and an f1-score of 90.8%. Tumor stage, history of other cancers, lymphatic invasion, tumor site, type of treatment, body weight, histological type, and addiction were identified as the most significant factors affecting gastric cancer survival.

Conclusions

This study proved the worth of the paired feature selection-classifier to identify the best path that could augment the five-year survival prediction in gastric cancer patients. Our results were better than those of previous studies, both in terms of the time required to form the models and the performance measurement criteria of the algorithms. These findings may be very promising and can, therefore, inform clinical decision-making and shed light on future studies.
Assessing the psychometric properties of persian version of Zarit Burden interview among family caregivers of patients with multiple sclerosis
Authors: Haghshenas Hajar , Jokar Zeinab , Zarshenas Ladan , Rakhshan Mahnaz , Poursadeghfard Maryam
Published: April 2023

Background

Caring for patients with multiple sclerosis (MS) imposes a great burden on caregivers and affects their lives in various aspects. This study aimed to evaluate the psychometric properties of Persian version of 22-item Zarit Burden Interview (ZBI-22) among family caregivers of patients with MS.

Methods

This methodological study was conducted in Fars province, southern of Iran. For this purpose, 120 family caregivers were recruited to participate in the study from January to March 2022. Zarit Burden Interview (ZBI) was translated into Persian through forward–backward method. Face and content validity were assessed. Construct validity was assessed using exploratory factor analyses (EFA), and its reliability was assessed by measuring internal consistency and testretest stability.

Results

According to face validity, the impact scores of all items were more than 1.5. Content validity ratio and content validity index values of all 22 items were 0.64-1 and 0.82-1, respectively. The scalelevel CVI/Ave was 0.97. Based on the results of factor analysis, five factors with eigenvalues more than 1 were extracted, which altogether explained 62.62% of the total variance of ZBI score. Among 22 items, one item was deleted during EFA validity assessment. Factor loading values ranged from 0.40 to 0.88. The reliability of the scale was confirmed (total Cronbach’s alpha of the ZBI = 0.88). Moreover, testretest stability assessment revealed no significant difference between test and retest scores (P > 0.05). The intraclass correlation (ICC) for the ZBI and ICCs among its factors were 0.88 and 0.6–0.86, respectively.

Conclusion

The Persian version of five-factor structure ZBI can be a valid and reliable scale, and it can be used to assess caregiver burden among family caregivers of patients with MS in Iran.
Strengthening open disclosure after incidents in maternity care: a realist synthesis of international research evidence
Authors: Adams Mary , Hartley Julie , Sanford Natalie , Heazell Alexander Edward , Iedema Rick , Bevan Charlotte , Booker Maria , Treadwell Maureen , Sandall Jane
Published: April 2023

Background

Open Disclosure (OD) is open and timely communication about harmful events arising from health care with those affected. It is an entitlement of service-users and an aspect of their recovery, as well as an important dimension of service safety improvement. Recently, OD in maternity care in the English National Health Service has become a pressing public issue, with policymakers promoting multiple interventions to manage the financial and reputational costs of communication failures. There is limited research to understand how OD works and its effects in different contexts.

Methods

Realist literature screening, data extraction, and retroductive theorisation involving two advisory stakeholder groups. Data relevant to families, clinicians, and services were mapped to theorise the relationships between contexts, mechanisms, and outcomes. From these maps, key aspects for successful OD were identified.

Results

After realist quality appraisal, 38 documents were included in the synthesis (22 academic, 2 training guidance, and 14 policy report). 135 explanatory accounts were identified from the included documents (with n = 41 relevant to families; n = 37 relevant to staff; and n = 37 relevant to services). These were theorised as five key mechanism sets: (a) meaningful acknowledgement of harm, (b) opportunity for family involvement in reviews and investigations, (c) possibilities for families and staff to make sense of what happened, (d) specialist skills and psychological safety of clinicians, and (e) families and staff knowing that improvements are happening. Three key contextual factors were identified: (a) the configuration of the incident (how and when identified and classified as more or less severe); (b) national or state drivers, such as polices, regulations, and schemes, designed to promote OD; and (c) the organisational context within which these these drivers are recieived and negotiated.

Conclusions

This is the first review to theorise how OD works, for whom, in what circumstances, and why. We identify and examine from the secondary data the five key mechanisms for successful OD and the three contextual factors that influence this. The next study stage will use interview and ethnographic data to test, deepen, or overturn our five hypothesised programme theories to explain what is required to strengthen OD in maternity services.
What barriers could impede access to mental health services for children and adolescents in Africa? A scoping review
Authors: Saade Sabine , Parent-Lamarche Annick , Khalaf Tatiana , Makke Sara , Legg Alexander
Published: April 2023

Background

Few studies have examined the mental health needs of African children and teenagers. Based on this gap, this scoping review aims to identify barriers to mental health services, treatments and services sought, and where mental health services are received.

Methods

To pursue the stated objectives, we searched the following databases a) PsycINFO, b) CINAHL, c) Medline, and d) Web of Science. The search yielded 15,956 records in total.

Results

Studies included in this review were conducted in six African countries: Ethiopia, Mali, Egypt, South Africa, Nigeria, and Tunisia. The majority of the studies were conducted in South Africa (33.32%), followed by Ethiopia (25%), and Egypt (16.67%). In terms of treatments and services sought, both professional and traditional/alternative treatments were reported. The most frequently noted services were psychiatric treatments (25%), screening and diagnostic assessment (16.67%), as well as psychiatric and psychological consultations (16.67%). The most frequently reported treatment centers were psychiatric hospitals. As for treatment barriers, the three most frequently encountered barriers were: a preference for traditional/alternative and complementary treatments (33.33%), followed by stigma (25%), and a lack of knowledge/unfamiliarity with the mental health condition (25%).

Conclusion

The results of this study are alarming due to the significant barriers to accessing mental health services coupled with the use of potentially harmful interventions to treat those mental health conditions. We hope this scoping review will help shed light on this important issue and help tomorrow’s generation reach its full potential.
Comparing a PD-L1 inhibitor plus chemotherapy to chemotherapy alone in neoadjuvant therapy for locally advanced ESCC: a randomized Phase II clinical trial
Authors: Li Yong , Zhou Aiping , Liu Shuoyan , He Ming , Chen Keneng , Tian Ziqiang , Li Yin , Qin Jianjun , Wang Zhen , Chen Haiquan , Tian Hui , Yu Yue , Qu Wang , Xue Liyan , He Shun , Wang Shuhang , Bie Fenglong , Bai Guangyu , Zhou Bolun , Yang Zhaoyang , Huang Huiyao , Fang Yan , Li Benjamin , Dai Xiangrong , Gao Shugeng , He Jie
Published: April 2023

Background

A Phase II study was undertaken to evaluate the safety and efficacy of the neoadjuvant socazolimab, a novel PD-L1 inhibitor, in combination with nab-paclitaxel and cisplatin for locally advanced esophageal squamous cell carcinoma (ESCC).

Methods

Sixty-four patients were randomly divided between the Socazolimab + nab-paclitaxel + cisplatin (TP) arm (n = 32) and the control arm (n = 32), receiving either socazolimab (5 mg/kg intravenously (IV), day 1) or a placebo with nab-paclitaxel (125 mg/m2 IV, day 1/8) and cisplatin (75 mg/m2 IV, day 1) repeated every 21 days for four cycles before surgery. The primary endpoint was major pathological response (MPR), and the secondary endpoints were pathological complete response (pCR), R0 resection rate, event-free survival (EFS), overall survival (OS), and safety.

Results

A total of 29 (90.6%) patients in each arm underwent surgery, and 29 (100%) and 28 (98.6%) patients underwent R0 resection in the Socazolimab + TP and Placebo + TP arms, respectively. The MPR rates were 69.0 and 62.1% (95% Confidence Interval (CI): 49.1–84.0% vs. 42.4–78.7%, P = 0.509), and the pCR rates were 41.4 and 27.6% (95% CI: 24.1–60.9% vs. 13.5–47.5%, P = 0.311) in the Socazolimab + TP and Placebo + TP arms, respectively. Significantly higher incidence rates of ypT0 (37.9% vs. 3.5%; P = 0.001) and T downstaging were observed in the Socazolimab + TP arm than in the Placebo + TP arm. The EFS and OS outcomes were not mature.

Conclusions

The neoadjuvant socazolimab combined with chemotherapy demonstrated promising MPR and pCR rates and significant T downstaging in locally advanced ESCC without increasing surgical complication rates.

Trial registration

Registration name (on clinicaltrials.gov): A Study of Anti-PD-L1 Antibody in Neoadjuvant Chemotherapy of Esophageal Squamous Cell Carcinoma. Registration number: NCT04460066.
Systematic pan-cancer analysis identifies SLC31A1 as a biomarker in multiple tumor types
Authors: Kong Fan-Sheng , Ren Chun-Yan , Jia Ruofan , Zhou Yuan , Chen Jian-Huan , Ma Yaping
Published: April 2023

Background

Solute Carrier Family 31 Member 1 (SLC31A1) has recently been identified as a cuproptosis-regulatory gene. Recent studies have indicated that SLC31A1 may play a role in colorectal and lung cancer tumorigenesis. However, the role of SLC31A1 and its cuproptosis-regulatory functions in multiple tumor types remains to be further elucidated.

Methods

Online websites and datasets such as HPA, TIMER2, GEPIA, OncoVar, and cProSite were used to extract data on SLC31A1 in multiple cancers. DAVID and BioGRID were used to conduct functional analysis and construct the protein–protein interaction (PPI) network, respectively. The protein expression data of SLC31A1 was obtained from the cProSite database.

Results

The Cancer Genome Atlas (TCGA) datasets showed increased SLC31A1 expression in tumor tissues compared with non-tumor tissues in most tumor types. In patients with tumor types including adrenocortical carcinoma, low-grade glioma, or mesothelioma, higher SLC31A1 expression was associated with shorter overall survival and disease-free survival. S105Y was the most prevalent point mutation in SLC31A1 in TCGA pan-cancer datasets. Moreover, SLC31A1 expression was positively correlated with the infiltration of immune cells such as macrophages and neutrophils in tumor tissues in several tumor types. Functional enrichment analysis showed that SLC31A1 co-expressed genes were involved in protein binding, integral components of the membrane, metabolic pathways, protein processing, and endoplasmic reticulum. Copper Chaperone For Superoxide Dismutase, Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha and Solute Carrier Family 31 Member 2 were copper homeostasis-regulated genes shown in the PPI network, and their expression was positively correlated with SLC31A1. Analysis showed there was a correlation between SLC31A1 protein and mRNA in various tumors.

Conclusions

These findings demonstrated that SLC31A1 is associated with multiple tumor types and disease prognosis. SLC31A1 may be a potential key biomarker and therapeutic target in cancers.
Digitally managed larviciding as a cost-effective intervention for urban malaria: operational lessons from a pilot in São Tomé and Príncipe guided by the Zzapp system
Authors: Vigodny Arbel , Ben Aharon Michael , Wharton-Smith Alexandra , Fialkoff Yonatan , Houri-Yafin Arnon , Bragança Fernando , Soares Da Graça Flavio , Gluck Dan , Alcântara Viegas D’Abreu João , Rompão Herodes
Published: April 2023

Background

Once a mainstay of malaria elimination operations, larval source management (LSM)—namely, the treatment of mosquito breeding habitats–has been marginalized in Africa in favour of long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS). However, the development of new technologies, and mosquitoes' growing resistance to insecticides used in LLINs and IRS raise renewed interest in LSM.

Methods

A digitally managed larviciding (DML) operation in three of the seven districts of São Tomé and Príncipe (STP) was launched by the Ministry of Health (MOH) and ZzappMalaria LTD. The operation was guided by the Zzapp system, consisting of a designated GPS-based mobile application and an online dashboard, which facilitates the detection, sampling and treatment of mosquito breeding sites. During the operation, quality assurance (QA) procedures and field management methods were developed and implemented.

Results

12,788 water bodies were located and treated a total of 128,864 times. The reduction impact on mosquito population and on malaria incidence was 74.90% and 52.5%, respectively. The overall cost per person protected (PPP) was US$ 0.86. The cost varied between areas: US$ 0.44 PPP in the urban area, and US$ 1.41 PPP in the rural area. The main cost drivers were labour, transportation and larvicide material.

Conclusion

DML can yield highly cost-effective results, especially in urban areas. Digital tools facilitate standardization of operations, implementation of QA procedures and monitoring of fieldworkers’ performance. Digitally generated spatial data also have the potential to assist integrated vector management (IVM) operations. A randomized controlled trial (RCT) with a larger sample is needed to further substantiate findings.
Changes in children’s and adolescents’ dietary intake after the implementation of Chile’s law of food labeling, advertising and sales in schools: a longitudinal study
Authors: Fretes Gabriela , Corvalán Camila , Reyes Marcela , Taillie Lindsey Smith , Economos Christina D. , Wilson Norbert L.W. , Cash Sean B.
Published: April 2023

Background

In June 2016, a comprehensive food policy was implemented in Chile that included front-of-package warning labels on key nutrients of concern (total sugars, added saturated fats, sodium, and calories), child-directed food advertisement bans, and school regulations. The policy was implemented in 3 phases from 2016 to 2019 and the primary objective was to improve children’s food environments. This study’s objective was to assess changes in child and adolescent intake of key nutrients of concern (total sugars, saturated fats, and sodium) at school after the initial implementation of Chile’s Law of Food Labeling and Advertisement.

Methods

Longitudinal study of 349 children from the Food Environment Chilean Cohort (FECHIC) and 294 adolescents from the Growth and Obesity Cohort Study (GOCS). Data were from single 24-hour dietary recalls collected from 2016 to 2019. Fixed-effects models stratified by school, home, and other locations compared nutrient consumption in each year to consumption at the pre-policy 2016 baseline. Nutrient intakes are expressed as percent of total energy.

Results

Compared to 2016 (pre-policy), total sugars consumed by children at school decreased 4.5 [-8.0, -0.9] percentage points (pp) and 11.8 [-15.4, -8.3] pp in 2018 and 2019 respectively. In 2019, children’s saturated fats and sodium intake at school also decreased (1.1 [-1.9, -0.2] pp and 10.3 [-18.1, -2.5] mg/100 kcal respectively). Likewise, in adolescents, total sugars and saturated fats consumed at school decreased in 2018 (5.3 [-8.4, -2.2] pp and 1.5 [-2.7, -0.3] pp respectively). However, consumption of key nutrients of concern at other locations increased after implementation of the policy.

Conclusions

After initial implementation of Chile’s Labeling Law, intake of most key nutrients of concern significantly declined at school. However, we found evidence of compensatory behavior in out-of-school settings. Further research is needed to evaluate what other actions are needed to impact overall diets in the long term both at schools and out of school.
MiR-146b-5p/SEMA3G regulates epithelial-mesenchymal transition in clear cell renal cell carcinoma
Authors: Tang Mengxi , Xiong Tao
Published: April 2023

Objective

The primary purpose was to unveil how the miR-146b-5p/SEMA3G axis works in clear cell renal cell carcinoma (ccRCC).

Methods

ccRCC dataset was acquired from TCGA database, and target miRNA to be studied was further analyzed using survival analysis. We performed miRNA target gene prediction through the database, and those predicted miRNAs were intersected with differential mRNAs. After calculating the correlation between miRNAs and mRNAs, we completed the GSEA pathway enrichment analysis on mRNAs. MiRNA and mRNA expression was examined by qRT-PCR. Western blot was introduced to detect SEMA3G, MMP2, MMP9 expression, epithelial-mesenchymal transition (EMT) marker proteins, and Notch/TGF-β signaling pathway-related proteins. Targeted relationship between miRNA and mRNA was validated using a dual-luciferase test. Transwell assay was employed to assess cell migration and invasion. Wound healing assay was adopted for evaluation of migration ability. The effect of different treatments on cell morphology was observed by a microscope.

Results

In ccRCC cells, miR-146b-5p was remarkably overexpressed, yet SEMA3G was markedly less expressed. MiR-146b-5p was capable of stimulating ccRCC cell invasion, migration and EMT, and promoting the transformation of ccRCC cell morphology to mesenchymal state. SEMA3G was targeted and inhibited via miR-146b-5p. MiR-146b-5p facilitated ccRCC cell migration, invasion, morphology transforming to mesenchymal state and EMT process by targeting SEMA3G and regulating Notch and TGF-β signaling pathways.

Conclusion

MiR-146b-5p regulated Notch and TGF-β signaling pathway by suppressing SEMA3G expression, thus promoting the growth of ccRCC cells, which provides a possible target for ccRCC therapy and prognosis prediction.
The lost balloon at midnight: a case report reveals the inevitability of heart team existence
Authors: Elbayomi Mohamed , Weyand Michael , Nooh Ehab , Harig Frank
Published: April 2023

Background

Dislodgement of a coronary stent-balloon catheter during percutaneous coronary intervention (PCI) is rare but is a life-threatening complication.

Case summary

A 57- year-old male presented with a non-ST elevation myocardial infarction (NSTEMI). Coronary angiography revealed total thrombotic occlusion of the Right coronary artery (RCA). Following the balloon dilatation of the RCA and while trying to retrieve the balloon catheter, the balloon was dislodged from the catheter shaft and entrapped in the coronary vessel. Under cardiopulmonary bypass, with antegrade cardioplegic arrest, the balloon was extracted through a coronary arteriotomy. Right coronary revascularization was done with reversed saphenous vein graft (SVG).

Discussion

Given the variety of equipment that can be retained in the coronary artery and the multitude of mechanisms by which it may be entrapped, there are no straightforward techniques applicable to all situations. Specific guidelines or recommendations on properly managing these potentially life-threatening complications do not exist. However, the most crucial issue in the management of these cases is the hemodynamic status of the patient as well as the coronary flow in the vessel with entrapped device or stent. In our case, the RCA was retrogradely perfused from the left coronary artery, which provided time to transfer the patient to cardiovascular surgical backup.
Pleural abrasion versus apical pleurectomy for primary spontaneous pneumothorax: a systematic review and Meta-analysis
Authors: Chang Jaewon , Ratnaraj Vignesh , Fu Vincent , Jiang Michael , Peri Varun , Nguyenhuy Minhtuan , Antippa Phillip
Published: April 2023

Background

Surgical approach is the most effective treatment for primary spontaneous pneumothorax. The two most widely adopted surgical methods are mechanical abrasion and apical pleurectomy, in addition to bullectomy. We performed a systematic review and meta-analysis to examine which technique is superior in treating primary spontaneous pneumothorax.

Methods

PubMed, MEDLINE and EMBASE databases were searched for studies published between January 2000 to September 2022 comparing mechanical abrasion and apical pleurectomy for treatment of primary spontaneous pneumothorax. The primary outcome was pneumothorax recurrence. Secondary outcomes included post-operative chest tube duration, hospital length of stay, operative time and intra-operative of blood loss.

Results

Eight studies were eligible for inclusion involving 1,613 patients. There was no difference in the rate of pneumothorax recurrence between pleural abrasion and pleurectomy (RR: 1.34; 95% CI: 0.94 to 1.92). However, pleural abrasion led to shorter hospital length of stay (MD: -0.25; 95% CI: -0.51 to 0.00), post-operative chest tube duration (MD: -0.30; 95% CI: -0.56 to -0.03), operative time (MD: -13.00; 95% CI -15.07 to 10.92) and less surgical blood loss (MD: -17.77; 95% CI: -24.36 to -11.18).

Conclusion

Pleural abrasion leads to less perioperative patient burden and shorter hospital length of stay without compromising the rate of pneumothorax recurrence when compared to pleurectomy. Thus, pleural abrasion is a reasonable first choice surgical procedure for management of primary spontaneous pneumothorax.
Flexible and efficient handling of nanopore sequencing signal data with slow5tools
Authors: Samarakoon Hiruna , Ferguson James M. , Jenner Sasha P. , Amos Timothy G. , Parameswaran Sri , Gamaarachchi Hasindu , Deveson Ira W.
Published: April 2023

Nanopore sequencing is being rapidly adopted in genomics. We recently developed SLOW5, a new file format with advantages for storage and analysis of raw signal data from nanopore experiments. Here we introduce slow5tools, an intuitive toolkit for handling nanopore data in SLOW5 format. Slow5tools enables lossless data conversion and a range of tools for interacting with SLOW5 files. Slow5tools uses multi-threading, multi-processing, and other engineering strategies to achieve fast data conversion and manipulation, including live FAST5-to-SLOW5 conversion during sequencing. We provide examples and benchmarking experiments to illustrate slow5tools usage, and describe the engineering principles underpinning its performance.
Study protocol for a randomized controlled trial of Proportional Assist Ventilation for Minimizing the Duration of Mechanical Ventilation: the PROMIZING study
Authors: Bosma Karen J. , Martin Claudio M. , Burns Karen E. A. , Mancebo Cortes Jordi , Suárez Montero Juan Carlos , Skrobik Yoanna , Thorpe Kevin E. , Amaral Andre Carlos Kajdacsy-Balla , Arabi Yaseen , Basmaji John , Beduneau Gaëtan , Beloncle Francois , Carteaux Guillaume , Charbonney Emmanuel , Demoule Alexandre , Dres Martin , Fanelli Vito , Geagea Anna , Goligher Ewan , Lellouche François , Maraffi Tommaso , Mercat Alain , Rodriguez Pablo O. , Shahin Jason , Sibley Stephanie , Spadaro Savino , Vaporidi Katerina , Wilcox M. Elizabeth , Brochard Laurent ,   On behalf of the Canadian Critical Care Trials Group and,   the REVA Network
Published: April 2023

Background

Proportional assist ventilation with load-adjustable gain factors (PAV+) is a mechanical ventilation mode that delivers assistance to breathe in proportion to the patient’s effort. The proportional assistance, called the gain, can be adjusted by the clinician to maintain the patient’s respiratory effort or workload within a normal range. Short-term and physiological benefits of this mode compared to pressure support ventilation (PSV) include better patient-ventilator synchrony and a more physiological response to changes in ventilatory demand.

Methods

The objective of this multi-centre randomized controlled trial (RCT) is to determine if, for patients with acute respiratory failure, ventilation with PAV+ will result in a shorter time to successful extubation than with PSV. This multi-centre open-label clinical trial plans to involve approximately 20 sites in several continents. Once eligibility is determined, patients must tolerate a short-term PSV trial and either (1) not meet general weaning criteria or (2) fail a 2-min Zero Continuous Positive Airway Pressure (CPAP) Trial using the rapid shallow breathing index, or (3) fail a spontaneous breathing trial (SBT), in this sequence. Then, participants in this study will be randomized to either PSV or PAV+ in a 1:1 ratio. PAV+ will be set according to a target of muscular pressure. The weaning process will be identical in the two arms. Time to liberation will be the primary outcome; ventilator-free days and other outcomes will be measured.

Discussion

Meta-analyses comparing PAV+ to PSV suggest PAV+ may benefit patients and decrease healthcare costs but no powered study to date has targeted the difficult to wean patient population most likely to benefit from the intervention, or used consistent timing for the implementation of PAV+. Our enrolment strategy, primary outcome measure, and liberation approaches may be useful for studying mechanical ventilation and weaning and can offer important results for patients.

Trial registration

ClinicalTrials.gov NCT02447692. Prospectively registered on May 19, 2015.
Human landing catches provide a useful measure of protective efficacy for the evaluation of volatile pyrethroid spatial repellents
Authors: Tambwe Mgeni Mohamed , Kibondo Ummi Abdul , Odufuwa Olukayode Ganiu , Moore Jason , Mpelepele Ahmed , Mashauri Rajabu , Saddler Adam , Moore Sarah Jane
Published: April 2023

Background

The human landing catch (HLC) method, in which human volunteers collect mosquitoes that land on them before they can bite, is used to quantify human exposure to mosquito vectors of disease. Comparing HLCs in the presence and absence of interventions such as repellents is often used to measure protective efficacy (PE). Some repellents have multiple actions, including feeding inhibition, whereby mosquitoes may be unable to bite even if they land on a host. A comparison was made between the PE of the volatile pyrethroid spatial repellent (VPSR) transfluthrin determined using a landing method (HLC) and a biting method (allowing the mosquitoes that landed to blood-feed) to evaluate whether HLC is a suitable method for the estimation of the personal PE of a VPSR.

Methods

A fully balanced, two-arm crossover design study was conducted using a 6 × 6 × 2-m netted cage within a semi-field system. Hessian strips (4 m × 0.1 m) treated with a 5-, 10-, 15-, or 20-g dose of transfluthrin were evaluated against a paired negative control for three strains of laboratory-reared Anopheles and Aedes aegypti mosquitoes. Six replicates were performed per dose using either the landing or the biting method. The number of recaptured mosquitoes was analysed by negative binomial regression, and the PEs calculated using the two methods were compared by Bland–Altman plots.

Results

For Anopheles, fewer mosquitoes blood-fed in the biting arm than landed in the landing arm (incidence rate ratio = 0.87, 95% confidence interval 0.81–0.93, P < 0.001). For Ae. aegypti, biting was overestimated by around 37% with the landing method (incidence rate ratio = 0.63, 95% confidence interval 0.57–0.70, P = 0.001). However, the PEs calculated for each method were in close agreement when tested by the Bland Altman plot.

Conclusions

The HLC method led to underestimation of mosquito feeding inhibition as a mode of action of transfluthrin, and there were species- and dose-dependent differences in the relationship between landing and biting. However, the estimated PEs were similar between the two methods. The results of this study indicate that HLC can be used as a proxy for personal PE for the evaluation of a VPSR, especially when the difficulties associated with enumerating blood-fed mosquitoes in a field setting are taken into consideration.

Graphical Abstract
Dysfunction in parkin aggravates inflammatory bone erosion by reinforcing osteoclast activity
Authors: Kim Eun-Young , Kim Ji-Eun , Kim Young-Eun , Choi Bongkun , Sohn Dong Hyun , Park Si-On , Chung Yeon-Ho , Kim Yongsub , Robinson William H. , Kim Yong-Gil , Chang Eun-Ju
Published: April 2023

Background

Parkin dysfunction associated with the progression of parkinsonism contributes to a progressive systemic skeletal disease characterized by low bone mineral density. However, the role of parkin in bone remodeling has not yet been elucidated in detail.

Result

We observed that decreased parkin in monocytes is linked to osteoclastic bone-resorbing activity. siRNA-mediated knockdown of parkin significantly enhanced the bone-resorbing activity of osteoclasts (OCs) on dentin without any changes in osteoblast differentiation. Moreover, Parkin-deficient mice exhibited an osteoporotic phenotype with a lower bone volume accompanied by increased OC-mediated bone-resorbing capacity displaying increased acetylation of α-tubulin compared to wild-type (WT) mice. Notably, compared to WT mice, the Parkin-deficient mice displayed increased susceptibility to inflammatory arthritis, reflected by a higher arthritis score and a marked bone loss after arthritis induction using K/BxN serum transfer, but not ovariectomy-induced bone loss. Intriguingly, parkin colocalized with microtubules and parkin-depleted-osteoclast precursor cells (Parkin−/− OCPs) displayed augmented ERK-dependent acetylation of α-tubulin due to failure of interaction with histone deacetylase 6 (HDAC6), which was promoted by IL-1β signaling. The ectopic expression of parkin in Parkin−/− OCPs limited the increase in dentin resorption induced by IL-1β, accompanied by the reduced acetylation of α-tubulin and diminished cathepsin K activity.

Conclusion

These results indicate that a deficiency in the function of parkin caused by a decrease in parkin expression in OCPs under the inflammatory condition may enhance inflammatory bone erosion by altering microtubule dynamics to maintain OC activity.
Dimethyl itaconate is effective in host-directed antimicrobial responses against mycobacterial infections through multifaceted innate immune pathways
Authors: Kim Young Jae , Park Eun-Jin , Lee Sang-Hee , Silwal Prashanta , Kim Jin Kyung , Yang Jeong Seong , Whang Jake , Jang Jichan , Kim Jin-Man , Jo Eun-Kyeong
Published: April 2023

Background

Itaconate, a crucial immunometabolite, plays a critical role in linking immune and metabolic functions to influence host defense and inflammation. Due to its polar structure, the esterified cell-permeable derivatives of itaconate are being developed to provide therapeutic opportunities in infectious and inflammatory diseases. Yet, it remains largely uncharacterized whether itaconate derivatives have potentials in promoting host-directed therapeutics (HDT) against mycobacterial infections. Here, we report dimethyl itaconate (DMI) as the promising candidate for HDT against both Mycobacterium tuberculosis (Mtb) and nontuberculous mycobacteria by orchestrating multiple innate immune programs.

Results

DMI per se has low bactericidal activity against Mtb, M. bovis Bacillus Calmette–Guérin (BCG), and M. avium (Mav). However, DMI robustly activated intracellular elimination of multiple mycobacterial strains (Mtb, BCG, Mav, and even to multidrug-resistant Mtb) in macrophages and in vivo. DMI significantly suppressed the production of interleukin-6 and -10, whereas it enhanced autophagy and phagosomal maturation, during Mtb infection. DMI-mediated autophagy partly contributed to antimicrobial host defenses in macrophages. Moreover, DMI significantly downregulated the activation of signal transducer and activator of transcription 3 signaling during infection with Mtb, BCG, and Mav.

Conclusion

Together, DMI has potent anti-mycobacterial activities in macrophages and in vivo through promoting multifaceted ways for innate host defenses. DMI may bring light to new candidate for HDT against Mtb and nontuberculous mycobacteria, both of which infections are often intractable with antibiotic resistance.
Sexual dimorphism in chronic respiratory diseases
Authors: Reddy Karosham Diren , Oliver Brian Gregory George
Published: April 2023

Sex differences in susceptibility, severity, and progression are prevalent for various diseases in multiple organ systems. This phenomenon is particularly apparent in respiratory diseases. Asthma demonstrates an age-dependent pattern of sexual dimorphism. However, marked differences between males and females exist in other pervasive conditions such as chronic obstructive pulmonary disease (COPD) and lung cancer. The sex hormones estrogen and testosterone are commonly considered the primary factors causing sexual dimorphism in disease. However, how they contribute to differences in disease onset between males and females remains undefined. The sex chromosomes are an under-investigated fundamental form of sexual dimorphism. Recent studies highlight key X and Y-chromosome-linked genes that regulate vital cell processes and can contribute to disease-relevant mechanisms. This review summarises patterns of sex differences in asthma, COPD and lung cancer, highlighting physiological mechanisms causing the observed dimorphism. We also describe the role of the sex hormones and present candidate genes on the sex chromosomes as potential factors contributing to sexual dimorphism in disease.
New stochastic fractional integral and related inequalities of Jensen–Mercer and Hermite–Hadamard–Mercer type for convex stochastic processes
Authors: Jarad Fahd , Sahoo Soubhagya Kumar , Nisar Kottakkaran Sooppy , Treanţă Savin , Emadifar Homan , Botmart Thongchai
Published: April 2023

In this investigation, we unfold the Jensen–Mercer ($\mathtt{J-M}$

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) inequality for convex stochastic processes via a new fractional integral operator. The incorporation of convex stochastic processes, the $\mathtt{J-M}$

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inequality and a fractional integral operator having an exponential kernel brings a new direction to the theory of inequalities. With this in mind, estimations of Hermite–Hadamard–Mercer ($\mathtt{H-H-M}$

H
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M

)-type fractional inequalities involving convex stochastic processes are presented. In the context of the new fractional integral operator, we also investigate a novel identity for differentiable mappings. Then, a new related $\mathtt{H-H-M}$

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-type inequality is presented using this identity as an auxiliary result. Applications to special means and matrices are also presented. These findings are particularly appealing from the perspective of optimization, as they provide a larger context to analyze optimization and mathematical programming problems.