bluuebunny/crossref_metadata_2025 huggingface dataset:
Computational physiological models for individualised mechanical ventilation: a systematic literature review focussing on quality, availability, and clinical readiness
Authors: Warnaar R. S. P. , Mulder M. P. , Fresiello L. , Cornet A. D. , Heunks L. M. A. , Donker D. W. , Oppersma E.
Published: July 2023

Background

Individualised optimisation of mechanical ventilation (MV) remains cumbersome in modern intensive care medicine. Computerised, model-based support systems could help in tailoring MV settings to the complex interactions between MV and the individual patient's pathophysiology. Therefore, we critically appraised the current literature on computational physiological models (CPMs) for individualised MV in the ICU with a focus on quality, availability, and clinical readiness.

Methods

A systematic literature search was conducted on 13 February 2023 in MEDLINE ALL, Embase, Scopus and Web of Science to identify original research articles describing CPMs for individualised MV in the ICU. The modelled physiological phenomena, clinical applications, and level of readiness were extracted. The quality of model design reporting and validation was assessed based on American Society of Mechanical Engineers (ASME) standards.

Results

Out of 6,333 unique publications, 149 publications were included. CPMs emerged since the 1970s with increasing levels of readiness. A total of 131 articles (88%) modelled lung mechanics, mainly for lung-protective ventilation. Gas exchange (n = 38, 26%) and gas homeostasis (n = 36, 24%) models had mainly applications in controlling oxygenation and ventilation. Respiratory muscle function models for diaphragm-protective ventilation emerged recently (n = 3, 2%). Three randomised controlled trials were initiated, applying the Beacon and CURE Soft models for gas exchange and PEEP optimisation. Overall, model design and quality were reported unsatisfactory in 93% and 21% of the articles, respectively.

Conclusion

CPMs are advancing towards clinical application as an explainable tool to optimise individualised MV. To promote clinical application, dedicated standards for quality assessment and model reporting are essential.

Trial registration number PROSPERO—CRD42022301715. Registered 05 February, 2022.
Development and validation of the creatinine clearance predictor machine learning models in critically ill adults
Authors: Huang Chao-Yuan , Güiza Fabian , Wouters Pieter , Mebis Liese , Carra Giorgia , Gunst Jan , Meersseman Philippe , Casaer Michael , Van den Berghe Greet , De Vlieger Greet , Meyfroidt Geert
Published: July 2023

Background

In critically ill patients, measured creatinine clearance (CrCl) is the most reliable method to evaluate glomerular filtration rate in routine clinical practice and may vary subsequently on a day-to-day basis. We developed and externally validated models to predict CrCl one day ahead and compared them with a reference reflecting current clinical practice.

Methods

A gradient boosting method (GBM) machine-learning algorithm was used to develop the models on data from 2825 patients from the EPaNIC multicenter randomized controlled trial database. We externally validated the models on 9576 patients from the University Hospitals Leuven, included in the M@tric database. Three models were developed: a “Core” model based on demographic, admission diagnosis, and daily laboratory results; a “Core + BGA” model adding blood gas analysis results; and a “Core + BGA + Monitoring” model also including high-resolution monitoring data. Model performance was evaluated against the actual CrCl by mean absolute error (MAE) and root-mean-square error (RMSE).

Results

All three developed models showed smaller prediction errors than the reference. Assuming the same CrCl of the day of prediction showed 20.6 (95% CI 20.3–20.9) ml/min MAE and 40.1 (95% CI 37.9–42.3) ml/min RMSE in the external validation cohort, while the developed model having the smallest RMSE (the Core + BGA + Monitoring model) had 18.1 (95% CI 17.9–18.3) ml/min MAE and 28.9 (95% CI 28–29.7) ml/min RMSE.

Conclusions

Prediction models based on routinely collected clinical data in the ICU were able to accurately predict next-day CrCl. These models could be useful for hydrophilic drug dosage adjustment or stratification of patients at risk.

Trial registration. Not applicable.
A study of the interaction space of two lactate dehydrogenase isoforms (LDHA and LDHB) and some of their inhibitors using proteochemometrics modeling
Authors: Damavandi Sedigheh , Shiri Fereshteh , Emamjomeh Abbasali , Pirhadi Somayeh , Beyzaei Hamid
Published: July 2023

Lactate dehydrogenase (LDH) is a tetramer enzyme that converts pyruvate to lactate reversibly. This enzyme becomes important because it is associated with diseases such as cancers, heart disease, liver problems, and most importantly, corona disease. As a system-based method, proteochemometrics does not require knowledge of the protein's three-dimensional structure, but rather depends on the amino acid sequence and protein descriptors. Here, we applied this methodology to model a set of LDHA and LDHB isoenzyme inhibitors. To implement the proteochemetrics method, the camb package in the R Studio Server programming environment was used. The activity of 312 compounds of LDHA and LDHB isoenzyme inhibitors from the valid Binding DB database was retrieved. The proteochemometrics method was applied to three machine learning algorithms gradient amplification model, random forest, and support vector machine as regression methods to find the best model. Through the combination of different models into an ensemble (greedy and stacking optimization), we explored the possibility of improving the performance of models. For the RF best ensemble model of inhibitors of LDHA and LDHB isoenzymes, and were 0.66 and 0.62, respectively. LDH inhibitory activation is influenced by Morgan fingerprints and topological structure descriptors.
MiR-3976 regulates HCT-8 cell apoptosis and parasite burden by targeting BCL2A1 in response to Cryptosporidium parvum infection
Authors: Li Juanfeng , Sun Lulu , Xie Fujie , Shao Tianren , Wu Shanbo , Li Xiaoying , Zhang Longxian , Wang Rongjun
Published: July 2023

Background

Cryptosporidium is second only to rotavirus as a cause of moderate-to-severe diarrhea in young children. There are currently no fully effective drug treatments or vaccines for cryptosporidiosis. MicroRNAs (miRNAs) are involved in regulating the innate immune response to Cryptosporidium parvum infection. In this study, we investigated the role and mechanism of miR-3976 in regulating HCT-8 cell apoptosis induced by C. parvum infection.

Methods

Expression levels of miR-3976 and C. parvum burden were estimated using real-time quantitative polymerase chain reaction (RT-qPCR) and cell apoptosis was detected by flow cytometry. The interaction between miR-3976 and B-cell lymphoma 2-related protein A1 (BCL2A1) was studied by luciferase reporter assay, RT-qPCR, and western blotting.

Results

Expression levels of miR-3976 were decreased at 8 and 12 h post-infection (hpi) but increased at 24 and 48 hpi. Upregulation of miR-3976 promoted cell apoptosis and inhibited the parasite burden in HCT-8 cells after C. parvum infection. Luciferase reporter assay indicated that BCL2A1 was a target gene of miR-3976. Co-transfection with miR-3976 and a BCL2A1 overexpression vector revealed that miR-3976 targeted BCL2A1 and suppressed cell apoptosis and promoted the parasite burden in HCT-8 cells.

Conclusions

The present data indicated that miR-3976 regulated cell apoptosis and parasite burden in HCT-8 cells by targeting BCL2A1 following C. parvum infection. Future study should determine the role of miR-3976 in hosts’ anti-C. parvum immunity in vivo.

Graphical Abstract
Metabolomics analysis reveals changes related to pseudocyst formation induced by iron depletion in Trichomonas vaginalis
Authors: Cheng Wei-Hung , Huang Po-Jung , Lee Chi-Ching , Yeh Yuan-Ming , Ong Seow-Chin , Lin Rose , Ku Fu-Man , Chiu Cheng-Hsun , Tang Petrus
Published: July 2023

Background

Iron is an essential element for cellular functions, such as energy metabolism. Trichomonas vaginalis, a human urogenital tract pathogen, is capable of surviving in the environment without sufficient iron supplementation. Pseudocysts (cyst-like structures) are an environmentally tolerated stage of this parasite while encountering undesired conditions, including iron deficiency. We previously demonstrated that iron deficiency induces more active glycolysis but a drastic downregulation of hydrogenosomal energy metabolic enzymes. Therefore, the metabolic direction of the end product of glycolysis is still controversial.

Methods

In the present work, we conducted an LC‒MS-based metabolomics analysis to obtain accurate insights into the enzymatic events of T. vaginalis under iron-depleted (ID) conditions.

Results

First, we showed the possible digestion of glycogen, cellulose polymerization, and accumulation of raffinose family oligosaccharides (RFOs). Second, a medium-chain fatty acid (MCFA), capric acid, was elevated, whereas most detected C18 fatty acids were reduced significantly. Third, amino acids were mostly reduced, especially alanine, glutamate, and serine. Thirty-three dipeptides showed significant accumulation in ID cells, which was probably associated with the decrease in amino acids. Our results indicated that glycogen was metabolized as the carbon source, and the structural component cellulose was synthesized at same time. The decrease in C18 fatty acids implied possible incorporation in the membranous compartment for pseudocyst formation. The decrease in amino acids accompanied by an increase in dipeptides implied incomplete proteolysis. These enzymatic reactions (alanine dehydrogenase, glutamate dehydrogenase, and threonine dehydratase) were likely involved in ammonia release.

Conclusion

These findings highlighted the possible glycogen utilization, cellulose biosynthesis, and fatty acid incorporation in pseudocyst formation as well as NO precursor ammonia production induced by iron-depleted stress.

Graphical Abstract
Effect of bromocriptine on glycemic control, risk of cardiovascular diseases and weight in patients with type 2 diabetes: a systematic review
Authors: Birhan Mulualem Tesfaye , Ayele Teklie Mengie , Abebe Fikire Wondimu , Dgnew Fiseha Nigussie
Published: July 2023

Background

Type 2 diabetes (T2DM) patients, including those in good glycemic control, have an increased risk of cardiovascular disease (CVD). Maintaining good glycemic control with drugs may reduce long-term CVD risk. Bromocriptine has been in clinical use for over 30 years, but the utility of bromocriptine in the treatment of diabetes patients has been proposed more recently.

Objective

To summarize the available data regarding the effect of bromocriptine in T2DM management.

Method

A systematic literature search was conducted in the electronic databases, including Google Scholar, PubMed, Medline, and Science Direct, to locate studies that meet the objectives of this systematic review. Additional articles were included by conducting direct Google searches of the references cited by eligible articles located by the database search. The following search terms were used on PubMed “bromocriptine OR dopamine agonist AND diabetes mellitus OR hyperglycemia OR obese”.

Result

Eight studies were included in the final analysis. 6210 of the 9391 study participants received bromocriptine treatment, while 3183 received a placebo. The studies demonstrated that patients who took bromocriptine treatment had significantly reduced blood glucose and BMI, which is the main cardiovascular risk factor in T2DM patients.

Conclusion

Based on this systematic review, bromocriptine may be used for T2DM treatment for its cardiovascular risk reduction effect, especially body weight reduction. However, advanced study designs might be warranted.
Epigenetic marks associated with gestational diabetes mellitus across two time points during pregnancy
Authors: Linares-Pineda Teresa , Peña-Montero Nerea , Fragoso-Bargas Nicolás , Gutiérrez-Repiso Carolina , Lima-Rubio Fuensanta , Suarez-Arana María , Sánchez-Pozo Antonio , Tinahones Francisco J. , Molina-Vega María , Picón-César María José , Sommer Christine , Morcillo Sonsoles
Published: July 2023

An adverse intrauterine or periconceptional environment, such as hyperglycemia during pregnancy, can affect the DNA methylation pattern both in mothers and their offspring. In this study, we explored the epigenetic profile in maternal peripheral blood samples through pregnancy to find potential epigenetic biomarkers for gestational diabetes mellitus (GDM), as well as candidate genes involved in GDM development. We performed an epigenome-wide association study in maternal peripheral blood samples in 32 pregnant women (16 with GDM and 16 non-GDM) at pregnancy week 24–28 and 36–38. Biochemical, anthropometric, and obstetrical variables were collected from all the participants. The main results were validated in an independent cohort with different ethnic origin (European = 307; South Asians = 165). Two hundred and seventy-two CpGs sites remained significantly different between GDM and non-GDM pregnant women across two time points during pregnancy. The significant CpG sites were related to pathways associated with type I diabetes mellitus, insulin resistance and secretion. Cg01459453 (SELP gene) was the most differentiated in the GDM group versus non-GDM (73.6 vs. 60.9, p = 1.06E−11; FDR = 7.87E−06). Three CpG sites (cg01459453, cg15329406, and cg04095097) were able to discriminate between GDM cases and controls (AUC = 1; p = 1.26E−09). Three differentially methylated positions (DMPs) were replicated in an independent cohort. To conclude, epigenetic marks during pregnancy differed between GDM cases and controls suggesting a role for these genes in GDM development. Three CpGs were able to discriminate GDM and non-GDM groups with high specificity and sensitivity, which may be biomarker candidates for diagnosis or prediction of GDM.
Fifty years of artisan entrepreneurship: a systematic literature review
Authors: Hasanah Uswatun , Sukoco Badri Munir , Supriharyanti Elisabeth , Wu Wann-Yih
Published: July 2023

Culturally based products and businesses have become increasingly common, drawing attention to artisan entrepreneurship. A small number of studies have comprehensively reviewed artisan entrepreneurship in terms of its antecedents and consequences, as is examined in this study. Specifically, this research looked at the factors that contribute to successful artisan entrepreneurship, managing environmental dynamism, markets, and institutional pressures. This study focuses on developing antecedents and consequences that may be used as a reference for the development of artisan entrepreneurship. A systematic literature review was conducted on 72 papers from the last 50 years from the first quartile of the Scopus database. This study identified that environmental, social, organizational, and individual factors could determine the development of artisan entrepreneurship and have consequences on social, organizational, and individual levels. This framework may aid artisan entrepreneurship and stakeholders in identifying the factors needed in the development of artisan entrepreneurship. The main elements of the resulting research agenda include suggestions for theory development, methodology, antecedents, and consequences.
The emerging roles of SUMOylation in the tumor microenvironment and therapeutic implications
Authors: Gu Yunru , Fang Yuan , Wu Xi , Xu Tingting , Hu Tong , Xu Yangyue , Ma Pei , Wang Qiang , Shu Yongqian
Published: July 2023

Tumor initiation, progression, and response to therapies depend to a great extent on interactions between malignant cells and the tumor microenvironment (TME), which denotes the cancerous/non-cancerous cells, cytokines, chemokines, and various other factors around tumors. Cancer cells as well as stroma cells can not only obtain adaption to the TME but also sculpt their microenvironment through a series of signaling pathways. The post-translational modification (PTM) of eukaryotic cells by small ubiquitin-related modifier (SUMO) proteins is now recognized as a key flexible pathway. Proteins involved in tumorigenesis guiding several biological processes including chromatin organization, DNA repair, transcription, protein trafficking, and signal conduction rely on SUMOylation. The purpose of this review is to explore the role that SUMOylation plays in the TME formation and reprogramming, emphasize the importance of targeting SUMOylation to intervene in the TME and discuss the potential of SUMOylation inhibitors (SUMOi) in ameliorating tumor prognosis.
Oxygen-loaded microbubble-mediated sonoperfusion and oxygenation for neuroprotection after ischemic stroke reperfusion
Authors: Ho Yi-Ju , Cheng Hsiang-Lung , Liao Lun-De , Lin Yu-Chun , Tsai Hong-Chieh , Yeh Chih-Kuang
Published: July 2023

Background

Ischemic stroke-reperfusion (S/R) injury is a crucial issue in the protection of brain function after thrombolysis. The vasodilation induced by ultrasound (US)-stimulated microbubble cavitation has been applied to reduce S/R injury through sonoperfusion. The present study uses oxygen-loaded microbubbles (OMBs) with US stimulation to provide sonoperfusion and local oxygen therapy for the reduction of brain infarct size and neuroprotection after S/R.

Methods

The murine S/R model was established by photodynamic thrombosis and thrombolysis at the remote branch of the anterior cerebral artery. In vivo blood flow, partial oxygen pressure (pO
2
), and brain infarct staining were examined to analyze the validity of the animal model and OMB treatment results. The animal behaviors and measurement of the brain infarct area were used to evaluate long-term recovery of brain function.

Results

The percentage of blood flow was 45 ± 3%, 70 ± 3%, and 86 ± 2% after 60 min stroke, 20 min reperfusion, and 10 min OMB treatment, respectively, demonstrating sonoperfusion, and the corresponding pO
2
level was 60 ± 1%, 76 ± 2%, and 79 ± 4%, showing reoxygenation. After 14 days of treatment, a 87 ± 3% reduction in brain infarction and recovery of limb coordination were observed in S/R mice. The expression of NF-κB, HIF-1α, IL-1β, and MMP-9 was inhibited and that of eNOS, BDNF, Bcl2, and IL-10 was enhanced, indicating activation of anti-inflammatory and anti-apoptosis responses and neuroprotection. Our study demonstrated that OMB treatment combines the beneficial effects of sonoperfusion and local oxygen therapy to reduce brain infarction and activate neuroprotection to prevent S/R injury.

Graphical Abstract
Cracking the code: unveiling the specific and shared mechanisms behind musculoskeletal interventions
Authors: McDevitt Amy W. , O’Halloran Bryan , Cook Chad E.
Published: July 2023

Background

Mechanisms reflect the steps or processes through which an intervention unfolds and produces change in a specified outcome variable. Mechanisms are responsible for determining “how treatments work” which has emerged as a critical question for both developing theory and enhancing treatment efficacy. Studies that evaluate “how” treatments work, not just “if” treatments work are of considerable importance.

Discussion

Specific and shared mechanisms research is a promising approach which aims to improve patient outcomes by tailoring treatments to the specific needs of each patient. Mechanisms research is an underexplored area of research requiring a unique research design.

Conclusion

Although mechanisms research is still in its infancy, prioritizing the study of the mechanisms behind manual therapy interventions can provide valuable insight into optimizing patient outcomes.
Comparison of survival for super high-flux hemodialysis (SHF-HD) with high albumin leakage versus online hemodiafiltration or SHF-HD with low albumin leakage: the SUPERB study
Authors: Okada Kazuyoshi , Tashiro Manabu , Michiwaki Hiroyuki , Inoue Tomoko , Shima Hisato , Minakuchi Jun , Kawashima Shu
Published: July 2023

Background

Survival is equivalent between super high-flux hemodialysis (SHF-HD) and online hemodiafiltration (OHDF) with similar albumin leakage. According to the 2013 Japanese dialyzer performance classification, survival on HD is optimal when a type II dialyzer (β2-microglobulin clearance ≥ 70 mL/min) is used. Here, we investigated whether survival could be improved by SHF-HD using a type II-b dialyzer (sieving coefficient for albumin ≥ 0.03) with high albumin leakage compared with OHDF or SHF-HD using a type II-a dialyzer (sieving coefficient for albumin < 0.03) with low albumin leakage.

Methods

This 3-year retrospective observational propensity score-matched study included 738 patients receiving SHF-HD (n = 310) or OHDF (n = 428) with a type II dialyzer at our institution between April 1 and July 1, 2017. Three-year all-cause mortality was compared for SHF-HD with high estimated albumin leakage (EAL) versus OHDF and SHF-HD with low EAL. Kaplan–Meier survival curves were compared using the log-rank test and hazard ratios were calculated by Cox regression analysis.

Results

Mortality in SHF-HD with high EAL was significantly lower than OHDF with low EAL (each n = 52 after matching; P = 0.007, log-rank test). All the dialyzers used a polyethersulfone (PES) membrane, whereas none of the hemodiafilters had a PES membrane. In SHF-HD, mortality was significantly lower when EAL was ≥ 3.0 g/session than when EAL was < 3.0 g/session (each n = 115 after matching, P = 0.004, log-rank test) and when the dialyzer used was type II-b rather than type II-a (each n = 133 after matching, P = 0.001, log-rank test).

Conclusions

These findings suggest that survival is better on SHF-HD using a type II-b dialyzer with high albumin leakage than on OHDF with low albumin leakage or SHF-HD using a type II-a dialyzers. The PES used in the type II-b dialyzer may also have a beneficial effect on survival.
Clinical impact of 99mTc-MAA SPECT/CT-based personalized predictive dosimetry in selective internal radiotherapy: a real-life single-center experience in unresectable HCC patients
Authors: Bucalau Ana-Maria , Collette Benoît , Tancredi Illario , Vouche Michael , Pezzullo Martina , Bouziotis Jason , Moreno-Reyes Rodrigo , Trotta Nicola , Levillain Hugo , Van Laethem Jean Luc , Verset Gontran
Published: July 2023

Background

Recent data demonstrated that personalized dosimetry-based selective internal radiotherapy (SIRT) is associated with better outcome for unresectable hepatocellular carcinoma (HCC).

Aim

We aim to evaluate the contribution of personalized predictive dosimetry (performed with Simplicity90® software) in our population of HCC patients by comparing them to our historical cohort whose activity was determined by standard dosimetry.

Methods

This is a retrospective, single-center study conducted between February 2016 and December 2020 that included patients with HCC who received SIRT after simulation based on either standard dosimetry (group A) or, as of December 2017, on personalized dosimetry (group B). Primary endpoints were best overall response (BOR) and objective response rate (ORR) evaluated by mRECIST at 3 months. Safety and toxicity profiles were evaluated at 1- and 3-months post-treatment. For group A we compared the activity to be administered determined a posteriori using Simplicit90Y® and the activity actually administered determined by the standard approach.

Results

Between February 2016 and December 2020, 66 patients received 69 simulations leading to 40 treatments. The median follow-up time was equal for both groups, 21 months (range 3–55) in group A and 21 months (range 4–39) in group B. The per patient analysis revealed a significant benefit of personalized predictive dosimetry in terms of better overall response at 3 months (80% vs. 33.3%, p = 0.007) and at 6 months (77.8% vs. 22.2%, p = 0.06). This trend was found in the analysis by nodule with a response rate according to mRECIST of 87.5% for personalized dosimetry versus 68.4% for standard dosimetry at 3 months, p = 0.24. Only one grade 3 biological toxicity (hyperbilirubinemia) was noted in group A. The comparison between the administered activity and the recommended activity recalculated a posteriori using Simplicit90Y® showed that the vast majority of patients who progressed (83.33%) received less activity than that recommended by the personalized approach or an inadequate distribution of the administered activity.

Conclusions

Our study aligns to recent literature and confirms that the use of personalized dosimetry allows a better selection of HCC patients who can benefit from SIRT, and consequently, improves the effectiveness of this treatment.
Insight of suicide in Iraq: a coroner’s report
Authors: Younis Maha Sulaiman , John Ann
Published: July 2023

Background

Suicide is a serious public health problems worldwide. Although suicide rates in the eastern Medetranian region are lower than western countries, increasing incidences is reported. This study aims to explore the demographic, clinical characteristics, and associated variables of people died by suicide in Iraq through a limited retrospective sample symbolized as biopsy.

Methods

The retrospective analysis included the electronic records of a hundred cases of suicide saved in the archives of the Medico-Legal Directory in Baghdad. Data were extracted from the legal investigation which included police investigations, family reports, and post-mortem reports. Simple descriptive satstistical analyses of the selected data was conducted.

Results

It estimated through this study that the crude rate of suicide was 1.75 per 100,000 population which is higher than 1.09/10,000, previously reported by the Iraq national study of suicide 2016. Most cases occurred in ≤ 29 years old, Muslims, city dwellers, and middle-class people aged 29 years or less. The prevalence of suicide was significantly associated with unemployment, good education, and income. The most common methods used were self-burning, gunshot, hanging, and jumping from heights. The reason for taking their own life was unknown for half of the sample. Depression was relatively common, while other mental disorders were of low rate or unrecognized. Family conflicts and environmental stressors were considered as motives.

Conclusions

This study exemplifies suicide patterns where young age, female gender, and violent methods are represented more than before, reflecting the impact of environmental and personal stressors and may be related to violence and the post-conflict situation initiated by the 2003 war. Little is known about suicide architecture due to stigma and poor surveillance system. A multidisciplinary suicide prevention strategy is crucial to implement in Iraq’s health service. Large-scale studies are called to cover the data gap.
Performative driven form finding in the early design stage
Authors: Elgohary Soha Mohamed , Abdin Ahmed Reda , Mohamed Raghad Mofeed
Published: July 2023

One of the most crucial factors architects should consider in building energy performance design is the energy consumption of residential buildings, particularly in megacities such as Cairo. Oxman classifies that a five-paradigmatic design model can help architects generate building forms. In this study, the authors aimed to develop a form-driven design framework based on a generative design model based on shape grammar that allows architects to generate building forms based on rules, which generate the building through variables that act as genes in the fitness function. The results indicate a significant framework that can help architects select the optimum building form that saves energy by enhancing daylight penetration and thermal and cooling loads on a building. Furthermore, after optimizing radiation and cooling load metrics, the form generated significant block and balcony arrangements, enhancing the shading in the eastern, western, and southern facades. In addition, the northern façade has been developed without block projections or balconies. Finally, the optimum window-to-wall ratio generated to balance spatial daylight autonomy (SDA) and annual sunlight exposure (ASE) lighting metrics for the north facade is 60% and for the southern, western, and eastern facades 10%.
Excluding autism or excluding everything? The problem of broad definitions in the England and Wales Draft Mental Health Bill
Authors: Beazley Peter
Published: July 2023

The recent Draft Mental Health Bill for England and Wales proposes changes to the Mental Health Act 1983 which will include, for the first time, a legal definition of autism. This article explores the specific potential issue that the definition, owing to its breadth, potentially encompasses a number of conditions other than autism, consequently leaving the definitionally dependent concept of ‘psychiatric disorder’ significantly narrowed in scope. The potential implications of this – primarily the concern that a range of other conditions and presentations could be unintentionally excluded from the scope of the civil powers in the Mental Health Act – are discussed.
Childhood attention-deficit hyperactivity disorder problems and mid-life cardiovascular risk: prospective population cohort study
Authors: Thapar Ajay K. , Riglin Lucy , Blakey Rachel , Collishaw Stephan , Davey Smith George , Stergiakouli Evie , Tilling Kate , Thapar Anita
Published: July 2023

Background

It is well-known that childhood attention-deficit hyperactivity disorder (ADHD) is associated with later adverse mental health and social outcomes. Patient-based studies suggest that ADHD may be associated with later cardiovascular disease (CVD) but the focus of preventive interventions is unclear. It is unknown whether ADHD leads to established cardiovascular risk factors because so few cohort studies measure ADHD and also follow up to an age where CVD risk is evident.

Aims

To examine associations between childhood ADHD problems and directly measured CVD risk factors at ages 44/45 years in a UK population-based cohort study (National Child Development Study) of individuals born in 1958.

Method

Childhood ADHD problems were defined by elevated ratings on both the parent Rutter A scale and a teacher-rated questionnaire at age 7 years. Outcomes were known cardiovascular risk factors (blood pressure, lipid measurements, body mass index and smoking) at the age 44/45 biomedical assessment.

Results

Of the 8016 individuals assessed both during childhood and at the biomedical assessment 3.0% were categorised as having childhood ADHD problems. ADHD problems were associated with higher body mass index (B = 0.92 kg/m2, s.d. = 0.27–1.56), systolic (3.5 mmHg, s.d. = 1.4–5.6) and diastolic (2.2 mmHg, s.d. = 0.8–3.6) blood pressure, triglyceride levels (0.24 mol/l, s.d. = 0.02–0.46) and being a current smoker (odds ratio OR = 1.6, s.d. = 1.2–2.1) but not with LDL cholesterol.

Conclusions

Childhood ADHD problems predicted multiple cardiovascular risk factors by mid-life. These findings, when taken together with previously observed associations with cardiovascular disease in registries, suggest that individuals with ADHD could benefit from cardiovascular risk monitoring, given these risk factors are modifiable with timely intervention.
Taking It to the States: Adapting Information Blocking Legislation to Oncology
Authors: Gerber David E.
Published: July 2023

Oncologists have successfully pushed for new state laws on how we release life-changing test results
Tumor Mutational Burden in Real-World Patients With Pancreatic Cancer: Genomic Alterations and Predictive Value for Immune Checkpoint Inhibitor Effectiveness
Authors: Quintanilha Julia C.F. , Storandt Michael H. , Graf Ryon P. , Li Gerald , Keller Rachel , Lin Douglas I. , Ross Jeffrey S. , Huang Richard S.P. , Schrock Alexa B. , Oxnard Geoffrey R. , Chakrabarti Sakti , Mahipal Amit
Published: July 2023

PURPOSE

Pancreatic ductal adenocarcinoma (PDAC) is largely considered a nonimmunogenic malignancy; however, approximately 1%, of patients may have tumors with deficient mismatch repair, high microsatellite instability, or high tumor mutational burden (TMB ≥10 mutations/Mb), which may be predictive of response to immune checkpoint inhibitor (ICI) therapy. We sought to analyze outcomes of patients with high-TMB and pathogenic genomic alterations observed in this population.

METHODS

This study included patients with PDAC who underwent comprehensive genomic profiling (CGP) at Foundation Medicine (Cambridge, MA). Clinical data were obtained from a US-wide real-world clinicogenomic pancreatic database. We report genomic alterations in those with high and low TMB, and compare outcomes on the basis of receipt of single-agent ICI or therapy regimens not containing ICI.

RESULTS

We evaluated 21,932 patients with PDAC who had tissue CGP data available, including 21,639 (98.7%) with low-TMB and 293 (1.3%) with high-TMB. Among patients with high-TMB, a greater number of alterations were observed in BRCA2, BRAF, PALB2, and genes of the mismatch repair pathway, whereas fewer alterations were observed in KRAS. Among patients who received an ICI (n = 51), those with high-TMB had more favorable median overall survival when compared with the low-TMB subset (25.7 v 5.2 months; hazard ratio, 0.32; 95% CI, 0.11 to 0.91; P = .034).

CONCLUSION

Longer survival was observed in patients with high-TMB receiving ICI compared with those with low-TMB. This supports the role of high-TMB as a predictive biomarker for efficacy of ICI therapy in PDAC. Additionally, we report higher rates of BRAF and BRCA2 mutations and lower rates of KRAS mutation among patients with PDAC and high-TMB, which to our knowledge, is a novel finding.
Inverse projection of axisymmetric orientation distributions
Authors: Kloza Philipp A. , Elliott James A.
Published: July 2023

We show that the projection of an axisymmetric three-dimensional orientation distribution to two dimensions can be cast into an Abel transform. Based on this correspondence, we derive an exact integral inverse, which allows for the quantification of three-dimensional uniaxial alignment of rod-like units from two-dimensional sliced images, thus providing an alternative to X-ray or tomographic analysis. A matrix representation of the projection and its inverse is derived, providing a direct relationship between two- and three-dimensional order parameters for both polar and non-polar systems.
Thermodynamic properties of substrate-induced graphene superlattice in homogeneous magnetic field
Authors: Prajapati Vivek , Deo Nivedita
Published: July 2023

In this article we study the thermodynamic properties of a

substrate-induced graphene superlattice in the presence of uniform magnetic field B. We derive an expression for the partition function of the system with uniform magnetic field B using the zeta function approach and find all related thermodynamic functions such as Helmholtz free energy, total energy, specific heat capacity and entropy for three cases related to the sublattice potential. We also show that the Dulong-Petit law is verified for all cases in the high-temperature limit. These results may shed light on the study of graphene superlattices in the developement of thermo-electric devices.
Glucagon-Like Peptide-1 Receptor Agonists Across the Spectrum of Heart Failure
Authors: Ferreira João Pedro , Sharma Abhinav , Butler Javed , Packer Milton , Zannad Faiez , Vasques-Nóvoa Francisco , Leite-Moreira Adelino , Neves João Sérgio
Published: July 2023

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been used to reduce body weight in overweight or people with obesity and to improve glycemic control and cardiovascular outcomes among people with type 2 diabetes (T2D) and a high cardiovascular risk. However, the effects of GLP-1 RAs may be modified by the presence of heart failure (HF). In this review, we summarize the evidence for the use of GLP-1 RA across a patient's risk with a particular focus on HF. After a careful review of the literature, we challenge the current views about the use of GLP-1 RAs and suggest performing active HF screening (with directed clinical history, physical examination, an echocardiogram, and natriuretic peptides) before initiating a GLP-1 RA. After HF screening, we suggest GLP-1 RA treatment decisions as follows: (1) in people with T2D without HF, GLP-1 RAs should be used for reducing the risk of myocardial infarction and stroke, with a possible effect to reduce the risk of HF hospitalizations; (2) in patients with HF and preserved ejection fraction, GLP-1 RAs do not reduce HF hospitalizations but may reduce atherosclerotic events, and their use may be considered in an individualized manner; and (3) in patients with HF and reduced ejection fraction, the use of GLP-1 RAs warrants caution due to potential risk of worsening HF events and arrhythmias, pending risk–benefit data from further studies.
SeriousMaricasand Their Male Concubines: Seeking Trans History and Intimacy in Argentine Police and Prison Records, 1921–1945
Authors: Fernández-Galeano Javier , Yarfitz Mir
Published: July 2023

State, legal, and medical experts in early twentieth-century Argentina conflated what would today be distinguished as same-sex attraction and trans or nonbinary gender experience. An urban subculture of self-styled maricas was pathologized by criminologists and occasionally targeted by police. Scholarship on these subjects has often focused on medical and cultural representation, situating maricas in the genealogy of homosexuality. This article brings insights from trans studies to several microhistories from police and prison archives in Rosario and Buenos Aires in order to focus on sociocultural practices. In their courtship rituals, romantic and sexual relationships, and household roles, Emilia, Dora, and La Lita engaged both respectability and sexual playfulness as modes of feminine expression.
Development of a Randomized Trial Comparing ICP-Monitor–Based Management of Severe Pediatric Traumatic Brain Injury to Management Based on Imaging and Clinical Examination Without ICP Monitoring–Study Protocol
Authors: Chesnut Randall , Temkin Nancy , Pridgeon James , Sulzbacher Stephen , Lujan Silvia , Videtta Walter , Moya-Barquín Luis , Chaddock Kelley , Bonow Robert , Petroni Gustavo , Guadagnoli Nahuel , Hendrickson Peter , Ramírez Cortez Grimaldo , Carreazo Nilton Yhuri , Vargas Aymituma Alcides , Anchante Daniel , Caqui Patrick , Ramírez Alberto , Munaico Abanto Manuel , Ortiz Chicchon Manuel , Cenzano Ramos José , Mazate-Mazariegos Analy , Castro Darce María del Carmen , Sierra Morales Roberto , Brol Lopez Pedro , Menendez Willy , Posadas Gutierrez Sofía , Kevin Vicente , Mazariegos Andrea , de Leon Elie , Rodas Barrios Rodolfo Enrique , Rodríguez Sandra , Flores Sandra , Alvarado Ovidio , Guzman Flores Luis José , Moisa Martinez Melvin , Gonzalez Pablo
Published: July 2023

BACKGROUND AND OBJECTIVES:

Traumatic brain injury (TBI) is a major global public health problem. It is a leading cause of death and disability in children and adolescents worldwide. Although increased intracranial pressure (ICP) is common and associated with death and poor outcome after pediatric TBI, the efficacy of current ICP-based management remains controversial. We intend to provide Class I evidence testing the efficacy of a protocol based on current ICP monitor–based management vs care based on imaging and clinical examination without ICP monitoring in pediatric severe TBI.

METHODS:

A phase III, multicenter, parallel-group, randomized superiority trial performed in intensive care units in Central and South America to determine the impact on 6-month outcome of children aged 1–12 years with severe TBI (age-appropriate Glasgow Coma Scale score ≤8) randomized to ICP-based or non-ICP–based management.

EXPECTED OUTCOMES:

Primary outcome is 6-month Pediatric Quality of Life. Secondary outcomes are 3-month Pediatric Quality of Life, mortality, 3-month and 6-month Pediatric extended Glasgow Outcome Score, intensive care unit length of stay, and number of interventions focused on treating measured or suspected intracranial hypertension.

DISCUSSION:

This is not a study of the value of knowing the ICP in sTBI. This research question is protocol-based. We are investigating the added value of protocolized ICP management to treatment based on imaging and clinical examination in the global population of severe pediatric TBI. Demonstrating efficacy should standardize ICP monitoring in severe pediatric TBI. Alternate results should prompt reassessment of how and in which patients ICP data should be applied in neurotrauma care.
Endothelin-1 as predictor of major adverse cardiovascular events in chronic coronary syndrome patients undergoing coronary intervention
Authors: Wasyanto Trisulo , Yasa Ahmad , Ayu Nimas
Published: July 2023

Background: Major adverse cardiovascular events (MACE) are predicted to be low in chronic coronary syndrome (CCS) patients who have undergone percutaneous coronary intervention (PCI). Endothelin-1 has been considered a pro inflammatory biomarker and suggested as a novel prognostic indicator in CCS. The objective of this research was to prove endothelin- 1 as predictor of MACE within 1-year evaluation in CCS patients undergoing PCI.

Methods: This research was an analytic observational study with a cohort design. The participants were CCS patients who had undergone PCI. Endotelin-1 levels were checked before the patient underwent PCI. Occurrences of MACE were observed within 1 year. The comparison between normally distributed continuous data was performed with a T-test, and the Mann–Whitney test was used for not normally distributed data. A comparison between categorical data was performed with the Chi-square test. The cut-off point of endothelin-1 levels to predict MACE was analyzed by receiver operating characteristics (ROC).

Results: Participants in this study were 63 patients. Six patients experienced MACE within 1 year (9.5%) and 57 patients were included in the non-MACE group (90.5%). Mann Whitney T test showed there were significance differences in endothelin-1 levels from the two groups (p=0.022). The ROC curve showed cut off point the endothelin-1 is 4.07 ng/dl with a sensitivity of 83.3%, specificity of 75.4% and accuracy of 76.2% for the occurrence of MACE. Based on the area under curve (AUC) value and the accuracy of this study, endothelin-1 was able to detect MACE within 1 year of follow-up.

Conclusions: Endothelin-1 can be used as predictor of MACE within 1-year evaluation in CCS patients undergoing coronary intervention.
Prevalence and risk factors associated with dysglycemia among overweight and obese Palestinian children in the Hebron governorate
Authors: Abu Al-Halawa Diala , Vicuna Polo Stephanny , Qasrawi Radwan
Published: July 2023

Background: The prevalence of dysglycemia among adolescents and younger children has been rising, yet health professionals are still unaware of the significance of this problem. According to the Palestinian Ministry of Health (MOH) records, most diabetic children under the age of 20 in Palestine are classified as type I; nonetheless, very limited data are available for policymakers to frame cost-effective screening programs. This study aims to determine the prevalence of dysglycemia in a sample of obese and overweight Palestinian children, identify risk factors associated with dysglycemia, and examine risk factors variance by gender.

Methods: A cross-sectional sample of observed obese and overweight children was selected from public schools in the Hebron governorate. Informed consent, physical examination, anthropometric, and laboratory tests (Blood Glucose Level (BGL) and fasting BGL ) were performed on a sample of 511 students (44.6% boys and 55.4% girls) aged 13–18-years (13-15 years =46.2% and 16-18 years =53.8%).

Results: The prevalence of confirmed overweight and obese cases was 73.2%, and dysglycemia prevalence among the confirmed cases was 3.7% (5.3% boys and 2.5% girls). The BMI classifications of the prediabetic children indicated that 42.1% were overweight and 31.1% were obese. Furthermore, 6.7% reported hypertension (both systolic and diastolic hypertension).

Conclusions: The results of this study provide valuable information about the rising problem of dysglycemia among Palestinian children and underlines the need for rapid screening programs and protocols for early detection and classification of the disease, leading to initiation of early prevention and treatment plans.
Quantification of microbial risk associated with fecal exposure in a nomadic lifestyle; case study of Turbi ward, Marsabit County
Authors: Jaro Batula , Wandili Sarah , Gakii Grace , Karani Caroline
Published: July 2023

Background: Water, Sanitation and Hygiene (WASH) is the cornerstone for health and growth at all stages of life in helping to maintain health and increase in life span. Poor sanitation as lead to disease causing microorganisms such as E. coli to be on the rise. This study aimed to determine water and milk contamination of E. coli from nomadic community.

Methods: A cross-sectional study was conducted on water and milk samples using most probable number method to determine contamination as a result of poor sanitation in this community.

Results: The dominant exposure pathway in this study was water pathway with high E. coli positivity, 20% (n=50) for dam water sampled, 20% (n=50) for pan and borehole feed water tanks 20% (n=50). Dam water sources analyzed had presence of 1.05 x1107CFU/ml and pan water sources 1.93x104 CFU/ml, which is above acceptable E. coli level in water for consumption is (10-40 CFU/ml)    

Conclusions: Microbial contamination noted from this study indicates that there is poor sanitation in nomadic lifestyle. This study reaffirms the need for elaborate sanitation model tailored to the need of pastoralist community to reduce perennial faucal contamination of water sources for the community of Turbi ward. Elaborate sanitation model tailored to the need of pastoralist community to reduce perennial fecal contamination of water sources for the community of Turbi ward.
Development of Communication Skills of Second-Graders: Features of the Implementation of the Requirements of the Federal State Educational Standard of Primary General Education
Authors: Romanova V.
Published: July 2023

The article analyzes the difficulties in implementing the updated versions of the Federal State Educational Standard for Primary General Education and the Federal Educational Program for Primary General Education. The problem of developing the communicative skills of second-graders is considered, the ways of teaching younger students to communicate in the dialogue mode are updated. As a priority, it is proposed to use forms of joint activities that meet the requirements of the updated program documents. It is noted the need for the gradual formation in children of the ability to listen to the interlocutor and perceive information to complete educational tasks. Tasks for second-graders are offered, which help students understand the importance of mastering communication skills in the process of studying the Russian language course.
A dialética da liberdade econômica e dos direitos sociais no marco da indústria 5.0.
Authors: Nahas Thereza Christina
Published: July 2023

O direito do trabalho vive uma fratura resultante de mudanças econômicas e sociais. A tecnologia tem impactado fortemente as relações de trabalho e incidido de modo incisivo na movimentação de trabalhadores e em suas aspirações e expectativas que já não se amoldam ao tradicional contrato de trabalho. As atuais configurações das empresas devem levar em conta o ser humano e devem ter objetivos que vão além do lucro, sendo essencial que desempenhem um papel fundamental no desenvolvimento social e na melhoria de qualidade de vida do trabalhador, independentemente da natureza do vínculo contratual que com ele estabeleça. E absolutamente necessário que o direito do trabalho possa viabilizar o entrosamento e o diálogo entre o social e o econômico. A essência do direito do trabalho seve voltar-se a aproximação da classe trabalhadora e empregador independente do grau de subordinação ou independência que caracterize a relação de trabalho. É chegada a hora de olhar criticamente os fatos que causaram a rachadura do direito do trabalho e construir uma ciência de aproximação e não de afastamento entre as partes do contrato de trabalho, em importar a natureza do vínculo que mantenham. A tecnologia deve permitir essa aproximação e ser aplicada para melhorar a condição humana.