bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness of an oral health curriculum in reducing dental caries increment and improving oral hygiene behaviour among schoolchildren of Ernakulam district in Kerala, India: study protocol for a cluster randomised trial
Authors: Das Hindol , Janakiram Chandrashekar , Ramanarayanan Venkitachalam , Karuveettil Vineetha , Kumar Vijay , Balachandran Parvathy , Varma Balagopal , John Denny
Published: February 2023

Introduction

Children’s learning abilities suffer when their oral health is compromised. Inadequate oral health can harm children’s quality of life, academic performance, and future success and achievements. Oral health problems may result in appetite loss, depression, increased inattentiveness, and distractibility from play and schoolwork, all of which can lower self-esteem and contribute to academic failure. An oral health curriculum, in addition to the standard school curriculum, may instil preventive oral hygiene behaviour in school students, enabling them to retain good oral health for the rest of their lives. Because most children attend school, the school setting is the most effective for promoting behavioural change in children. A ‘health-promoting school’ actively promotes health by enhancing its ability to serve as a healthy place to live, learn and work, bringing health and education together. Making every school a health-promoting school is one of the joint objectives of the WHO and UNICEF. The primary objective of this proposed study is to assess the effectiveness of an oral health curriculum intervention in reducing dental caries incidence and improving oral hygiene behaviour among high school children in grades 8–10 of the Ernakulam district in Kerala, India. If found to be effective in changing children’s behaviour in a positive way, an oral health curriculum may eventually be incorporated into the school health curriculum in the future. Classroom interventions can serve as a cost-effective tool to increase children’s oral health awareness.

Methods and analysis

This protocol presents a cluster randomised trial design. It is a parallel-group comparative trial with two arms having a 1:1 distribution—groups A and B with oral health curriculum intervention from a dental professional and a schoolteacher, respectively. High schools (grades 8–10) will be selected as clusters for the trial. The minimum cluster size is 20 students per school. The total sample size is 2000 high school children. Data will be collected at three time points, including baseline, after 1 year (mid-term) and 2 years (final), respectively. The outcome measures are Decayed, Missing and Filled Teeth Index; Oral Hygiene Index-Simplified; and knowledge, attitude and behaviour. Data collection will be done by clinical oral examination and questionnaire involving oral health-related knowledge, attitude and behaviour items.

Ethics and dissemination

Ethical approval was obtained from the Institutional Ethics Committee of Amrita Institute of Medical Sciences and Research Centre (dated 19 July 2022, no: IEC-AIMS-2022-ASD-179).

Trial registration number

Clinical Trial Registry of India (CTRI/2022/09/045410).
Comparison of clinical characteristics and outcomes of critically ill adults with SARS-CoV-2 infection during Delta and Omicron variant predominance periods: a single-hospital retrospective cohort study
Authors: Sankar Keerthana , Modi Neil , Polyak Alexander , Directo Michael P , Johnson Lily R , Kho Norling , Isonaka Sharon K , Pedraza Isabel , Chen Peter , Modes Matthew E
Published: February 2023

Introduction

Initial reports suggest the B.1.1.529 (Omicron) variant of SARS-CoV-2 causes less severe disease compared with the B.1.617.2 (Delta) variant, though more widespread vaccination contributed to these findings. Little is known about clinical characteristics and outcomes of patients with SARS-CoV-2 infection requiring intensive care during periods of Delta and Omicron variant predominance.

Aim

To examine and compare characteristics of critically ill adults with SARS-CoV-2 infection during periods of Delta and Omicron variant predominance.

Methods

We conducted a retrospective cohort study of critically ill adults with SARS-CoV-2 infection at one academic hospital in Los Angeles during Delta (15 July 2021–23 September 2021) and Omicron (21 December 2021–27 January 2022) predominance. Patient characteristics were compared between Delta-period and Omicron-period hospitalisations, overall and stratified by vaccination status.

Results

79 adults required intensive care during the Delta predominance period and 116 during the Omicron predominance period. We found similar proportions of intensive care unit admissions occurring in fully vaccinated patients between the two periods, despite Los Angeles County data revealing an almost 60% increase in the proportion of SARS-CoV-2 hospitalisations occurring in fully vaccinated persons. There was no difference in the need for invasive mechanical ventilation (IMV). Among those who required IMV, the median duration of IMV was shorter overall (Delta=18 days; Omicron=8 days; p=0.006) and among unvaccinated persons (Delta=19 days; Omicron=8.5 days; p=0.018). Among unvaccinated persons, the median intensive care unit length of stay was shorter (Delta=12 days; Omicron=5 days; p=0.037) during Omicron predominance. There was no difference in the proportion of patients who died while hospitalised.

Conclusions

In this single-hospital study, critically ill patients with SARS-CoV-2 infection experienced less severe respiratory disease during Omicron predominance, likely due to reduced variant-specific virulence. Vaccination likely reduced development of critical illness in adults with SARS-CoV-2 infection during Omicron predominance.
Distinct phenotypes of kidney transplant recipients aged 80 years or older in the USA by machine learning consensus clustering
Authors: Thongprayoon Charat , Jadlowiec Caroline C , Mao Shennen A , Mao Michael A , Leeaphorn Napat , Kaewput Wisit , Pattharanitima Pattharawin , Nissaisorakarn Pitchaphon , Cooper Matthew , Cheungpasitporn Wisit
Published: February 2023

Objectives

This study aimed to identify distinct clusters of very elderly kidney transplant recipients aged ≥80 and assess clinical outcomes among these unique clusters.

Design

Cohort study with machine learning (ML) consensus clustering approach.

Setting and participants

All very elderly (age ≥80 at time of transplant) kidney transplant recipients in the Organ Procurement and Transplantation Network/United Network for Organ Sharing database database from 2010 to 2019.

Main outcome measures

Distinct clusters of very elderly kidney transplant recipients and their post-transplant outcomes including death-censored graft failure, overall mortality and acute allograft rejection among the assigned clusters.

Results

Consensus cluster analysis was performed in 419 very elderly kidney transplant and identified three distinct clusters that best represented the clinical characteristics of very elderly kidney transplant recipients. Recipients in cluster 1 received standard Kidney Donor Profile Index (KDPI) non-extended criteria donor (ECD) kidneys from deceased donors. Recipients in cluster 2 received kidneys from older, hypertensive ECD deceased donors with a KDPI score ≥85%. Kidneys for cluster 2 patients had longer cold ischaemia time and the highest use of machine perfusion. Recipients in clusters 1 and 2 were more likely to be on dialysis at the time of transplant (88.3%, 89.4%). Recipients in cluster 3 were more likely to be preemptive (39%) or had a dialysis duration less than 1 year (24%). These recipients received living donor kidney transplants. Cluster 3 had the most favourable post-transplant outcomes. Compared with cluster 3, cluster 1 had comparable survival but higher death-censored graft failure, while cluster 2 had lower patient survival, higher death-censored graft failure and more acute rejection.

Conclusions

Our study used an unsupervised ML approach to cluster very elderly kidney transplant recipients into three clinically unique clusters with distinct post-transplant outcomes. These findings from an ML clustering approach provide additional understanding towards individualised medicine and opportunities to improve care for very elderly kidney transplant recipients.
Anticoagulation helps shrink giant venous lakes and arteriovenous fistulas in dural sinus malformation
Authors: Saliou Guillaume , Deiva Kumaran , Möhlenbruch Markus A , Lubicz Boris
Published: February 2023

Background

Dural sinus malformations (DSMs) associated with high flow arteriovenous shunts are a challenging disease in babies that can lead to severe neurological damage or death. We report our treatment strategy in seven consecutive DSMs.

Methods

We performed a retrospective analysis of seven consecutive patients from four centres, treated with transarterial embolization and anticoagulants.

Results

Mean clinical and imaging follow-up was 2.8 years (IQR1–31.8–5.3). At baseline, the median size of the dilated venous pouch (giant lake) was 35 mm (IQR1–324–41) that decreased to a normal or near normal venous collector diameter of median size 11.5 mm (IQR1–38.5–13.8). This was achieved after a median of two embolization sessions targeted on dural feeders (IQR1–31.5–2.5), leaving associated pial feeders untreated. There were no cerebral hemorrhagic complications during the anticoagulation treatment. Median percentage of shunt remaining after embolization was 30% (IQR1–312–30), which spontaneously decreased with anticoagulation and even after discontinuation of anticoagulation, in parallel with the reduction in diameter of the dilated sinus, up to healing (or near healing). At the last clinical assessment, the modified Rankin Scale score was 0 in four patients, 1 in one patient, and 3 in two patients.

Conclusions

Anticoagulants may help to potentiate transarterial embolization in DSMs in babies by decreasing venous dilatation and reducing the remaining arteriovenous shunt, particularly the pial feeders. We did not observe recurrence of arteriovenous shunts after treatment, especially during anticoagulation treatment. Further studies are needed to support our findings.
Tracheostomy in children is associated with neutrophilic airway inflammation
Authors: Powell Jason , Powell Steven , Mather Michael W , Beck Lauren , Nelson Andrew , Palmowski Pawel , Porter Andrew , Coxhead Jonathan , Hedley Ann , Scott Jonathan , Rostron Anthony J , Hellyer Thomas P , Zaidi Fatima , Davey Tracey , Garnett James P , Agbeko Rachel , Ward Chris , Stewart Christopher J , Taggart Clifford C , Brodlie Malcolm , Simpson A John
Published: February 2023

Background

Tracheostomies in children are associated with significant morbidity, poor quality of life, excess healthcare costs and excess mortality. The underlying mechanisms facilitating adverse respiratory outcomes in tracheostomised children are poorly understood. We aimed to characterise airway host defence in tracheostomised children using serial molecular analyses.

Methods

Tracheal aspirates, tracheal cytology brushings and nasal swabs were prospectively collected from children with a tracheostomy and controls. Transcriptomic, proteomic and metabolomic methods were applied to characterise the impact of tracheostomy on host immune response and the airway microbiome.

Results

Children followed up serially from the time of tracheostomy up to 3 months postprocedure (n=9) were studied. A further cohort of children with a long-term tracheostomy were also enrolled (n=24). Controls (n=13) comprised children without a tracheostomy undergoing bronchoscopy. Long-term tracheostomy was associated with airway neutrophilic inflammation, superoxide production and evidence of proteolysis when compared with controls. Reduced airway microbial diversity was established pre-tracheostomy and sustained thereafter.

Conclusions

Long-term childhood tracheostomy is associated with a inflammatory tracheal phenotype characterised by neutrophilic inflammation and the ongoing presence of potential respiratory pathogens. These findings suggest neutrophil recruitment and activation as potential exploratory targets in seeking to prevent recurrent airway complications in this vulnerable group of patients.
Passive tracer transport in peristaltic pumping of non-Newtonian blood flow: A mathematical model
Authors: Anwar Bég O. , Roy Ashis Kumar
Published: February 2023

The large time behavior of passive contaminant in non-Newtonian peristaltic blood flow in a two-dimensional (2D) channel (capillary) has been examined in this paper. The power-law model is employed in order to highlight the non-Newtonian blood characteristic. The study was conducted using the Reynolds decomposition technique, which converts a 2D transport problem into a 1D transport model in which species concentration can be decomposed into sectional average concentration and variation from its mean value. For flow velocity, the same decomposition method is used. This allows the derivation of the dispersion coefficient and convection coefficient. Using Fick’s law, the advection–diffusion equation is modified by replacing these coefficients by their corresponding average values and analytical solutions for the mean concentration are derived. In the absence of peristalsis effects ([Formula: see text]), i.e., for the straight rigid channel, the dispersion coefficient is invariant along the channel length. With increasing modulation (peristaltic wave) parameter, [Formula: see text], there is a strong elevation in advection coefficient in the initial half of the channel with a subsequent suppression in the second half of the channel, indicating that the location in the channel strongly influences advection characteristics. Advection coefficient is significantly elevated with increment in power-law rheological index (for shear-thinning fluids, [Formula: see text]) across the channel length and exhibits an oscillatory nature due to the peristaltic waves. In the shear-thickening range ([Formula: see text]), with progressive increase in n, an increment in peristaltic modulation parameter, [Formula: see text], induces a marked reduction in the axially average relative advection coefficient. Dispersion coefficient is initially boosted along the early section of the channel with increment in modulation parameter whereas further long the channel this trend is reversed. Increasing aspect ratio and Péclet number consistently boost dispersion coefficient along the entire channel length. The study provides a solid benchmark for further generalized simulations with computational fluid dynamics.
Differential-thermal analysis and a microscopic study of the effect of γ-radiation on CuTlSe2 single crystal
Authors: Madatov Rahim , Mamishova Rakshana , Abasova Adila , Alahverdiyev Shamsaddin
Published: February 2023

Herein, the X-ray phase analysis (XPA) and differential-thermal analysis (DTA) of the CuTlSe2 compound obtained by the Bridgman–Stockbarger method have been investigated. As a result of the study, the values of energy absorption and mass losses of CuTlSe2 single crystal have been estimated depending on the temperature given their change mechanisms. The surface morphology of single crystals of the ternary coppercopounds (Cu-Tl-X ([Formula: see text])) in the initial state, annealing and after exposure to gamma-radiation is studied by atomic force microscopy. It is shown that the surface relief undergoes modification in the absorbed dose region of [Formula: see text] 500[Formula: see text]krad.
A Review of the Use of 3D Printing Technology in Treatment of Scaphoid Fractures
Authors: LI Lily X. , KEDGLEY Angela E. , HORWITZ Maxim D.
Published: February 2023

Background: Three-dimensional (3D) printing technology is increasingly commercially viable for pre-surgical planning, intraoperative templating, jig creation and customised implant manufacture. The challenging nature of scaphoid fracture and nonunion surgery make it an obvious target. The aim of this review is to determine the use of 3D printed technologies in the treatment of scaphoid fractures.

Methods: This is a review of the Medline, Embase and Cochrane Library databases examining studies aimed at therapeutic use of 3D printing, also known as rapid prototyping or additive technology, in the treatment of scaphoid fractures. All studies published up to and including November 2020 were included in the search. Relevant data extracted included modality of use (as template/model/guide/prosthesis), operative time, accuracy of reduction, radiation exposure, follow-up duration, time to union, complications and study quality.

Results: A total of 649 articles were identified, of which 12 met the full inclusion criteria. Analysis of the articles showed that 3D printing techniques can be utilised in myriad ways to aid planning and delivery of scaphoid surgery. Percutaneous guides for Kirschner-wire (K-wire) fixation of non-displaced fractures can be created; custom guides can be printed to aid reduction of displaced or non-united fractures; patient-specific total prostheses may recreate near-normal carpal biomechanics and a simple model may help graft harvesting and positioning.

Conclusions: This review found that the use of 3D printed patient-specific models and templates in scaphoid surgery can improve accuracy and speed, and reduce radiation exposure. 3D printed prostheses may also restore near-normal carpal biomechanics without burning bridges for potential future procedures.

Level of Evidence: Level III (Therapeutic)
Bioventing revisited: efficacy of enhanced biodegradation for sites with mobile LNAPL
Authors: Smith Jonathon J. , Gaito Steven T. , Koons Brad W.
Published: February 2023

Bioventing is a remediation technology that enhances aerobic biodegradation of petroleum-affected soil in the vadose zone by introducing oxygen to the subsurface. Bioventing was historically considered effective for decreasing petroleum hydrocarbons concentrations in soil but discounted for sites where mobile light non-aqueous phase liquid (LNAPL) accumulated in wells. While the science behind bioventing has not changed, the conceptual understanding of LNAPL depletion processes and framework for evaluating the efficacy of LNAPL remediation technologies has changed markedly since the 1990s. This shift leads to a new perspective on the utility and effectiveness of bioventing compared to other LNAPL remedial alternatives.

A case study is used to illustrate that mass depletion by bioventing often outperforms hydraulic recovery over time. Biodegradation processes enhanced by bioventing deplete LNAPL constituents in mobile and residual LNAPL in the LNAPL smear zone, which means that bioventing can address a larger mass of LNAPL and may induce a beneficial composition change. Hydraulic LNAPL recovery technologies only access the mobile LNAPL and do not induce a composition change. Furthermore, for low LNAPL recoverability (transmissivity), bioventing typically uses less energy and produces less waste per unit mass of hydrocarbon removed than hydraulic recovery, making bioventing a more sustainable remedial technology.
Toward Interpretable Graph Tensor Convolution Neural Network for Code Semantics Embedding
Authors: Yang Jia , Fu Cai , Deng Fengyang , Wen Ming , Guo Xiaowei , Wan Chuanhao
Published: February 2023

Intelligent deep learning-based models have made significant progress for automated source code semantics embedding, and current research works mainly leverage natural language-based methods and graph-based methods. However, natural language-based methods do not capture the rich semantic structural information of source code, and graph-based methods do not utilize rich distant information of source code due to the high cost of message-passing steps.

In this article, we propose a novel interpretable model, called graph tensor convolution neural network (GTCN), to generate accurate code embedding, which is capable of comprehensively capturing the distant information of code sequences and rich code semantics structural information. First, we propose to utilize a high-dimensional tensor to integrate various heterogeneous code graphs with node sequence features, such as control flow, data flow. Second, inspired by the current advantages of graph-based deep learning and efficient tensor computations, we propose a novel interpretable graph tensor convolution neural network for learning accurate code semantic embedding from the code graph tensor. Finally, we evaluate three popular applications on the GTCN model: variable misuse detection, source code prediction, and vulnerability detection. Compared with current state-of-the-art methods, our model achieves higher scores with respect to the top-1 accuracy while costing less training time.
Nonphotic entrainment of central and peripheral circadian clocks in mice by scheduled voluntary exercise under constant darkness
Authors: Sato Ren Y. , Yamanaka Yujiro
Published: February 2023

In mammals, the central circadian pacemaker in the suprachiasmatic nucleus (SCN) entrains to an environmental light-dark (LD) cycle and organizes the temporal order of circadian rhythms in physiology and behavior. Previously, some studies have demonstrated that scheduled exercise could entrain the free-running behavior rhythm in nocturnal rodents. However, it remains unknown whether entrainment by scheduled exercise alters the internal temporal order of the behavioral circadian rhythms or clock gene expression in the SCN, extra-SCN brain regions, and peripheral organs when mice are entrained to the scheduled exercise under constant darkness (DD). In the present study, we examined circadian rhythms in locomotor activity and clock gene Per1 expression by bioluminescence reporter ( Per1-luc) in the SCN, arcuate nucleus (ARC), liver, and skeletal muscle of mice entrained to an LD cycle, mice free-running under DD, and mice entrained to daily exposure to a new cage with a running wheel (NCRW) under DD. All mice showed a steady-state entrainment of behavioral circadian rhythms to NCRW exposure under DD in parallel with shortening of the α when compared with that under DD. The temporal order of behavioral circadian rhythms and the Per1-luc rhythms in the SCN and peripheral tissues but not in the ARC were maintained in the mice entrained to the NCRW and LD cycles; in contrast, the temporal order was altered in the mice under DD. The present findings reveal that the SCN entrains to daily exercise, and daily exercise reorganizes the internal temporal order of behavioral circadian rhythms and clock gene expression in the SCN and peripheral tissues.
A Novel Study on Machine Learning Algorithm-Based Cardiovascular Disease Prediction
Authors: Khan Arsalan , Qureshi Moiz , Daniyal Muhammad , Tawiah Kassim
Published: February 2023

Cardiovascular disease (CVD) is a life-threatening disease rising considerably in the world. Early detection and prediction of CVD as well as other heart diseases might protect many lives. This requires tact clinical data analysis. The potential of predictive machine learning algorithms to develop the doctor’s perception is essential to all stakeholders in the health sector since it can augment the efforts of doctors to have a healthier climate for patient diagnosis and treatment. We used the machine learning (ML) algorithm to carry out a significant explanation for accurate prediction and decision making for CVD patients. Simple random sampling was used to select heart disease patients from the Khyber Teaching Hospital and Lady Reading Hospital, Pakistan. ML methods such as decision tree (DT), random forest (RF), logistic regression (LR), Naïve Bayes (NB), and support vector machine (SVM) were implemented for classification and prediction purposes for CVD patients in Pakistan. We performed exploratory analysis and experimental output analysis for all algorithms. We also estimated the confusion matrix and recursive operating characteristic curve for all algorithms. The performance of the proposed ML algorithm was estimated using numerous conditions to recognize the best suitable machine learning algorithm in the class of models. The RF algorithm had the highest accuracy of prediction, sensitivity, and recursive operative characteristic curve of 85.01%, 92.11%, and 87.73%, respectively, for CVD. It also had the least specificity and misclassification errors of 43.48% and 8.70%, respectively, for CVD. These results indicated that the RF algorithm is the most appropriate algorithm for CVD classification and prediction. Our proposed model can be implemented in all settings worldwide in the health sector for disease classification and prediction.
The Role of Microbiome in Psychiatric Diseases (Insomnia and Anxiety/Depression) with Microbiological Mechanisms
Authors: Niazi Madiha Khan , Hassan Farooq , Tufail Tabussam , ismail Muhammad Amjed , Riaz Khadija
Published: February 2023

More focus is being paid to the relationship between gastrointestinal microbiota and human health. The microbiota-gut-brain axis was created as a result of the intricate networks and connections between the gastrointestinal bacteria and the host, highlighting the significant impact that this environment may have on brain health and central nervous system problems. To communicate with the central nervous system, the gastrointestinal, autonomic, immune, neuroendocrine, and neuroendocrine systems engage in a bidirectional interaction with the microbiota. Through a number of neurological processes, including stimulation of the altered neurotransmitter function, hypothalamic-pituitary-adrenal axis, and immune system activity, changes in this network may have an impact on both health and sickness. Anxiety and sadness are two neuropsychiatric conditions that may be impacted by the microbiota-gut-brain axis, according to a recent study. Numerous host disorders, including obesity, diabetes, and inflammation, have already been related to alterations in the gut microbiota’s makeup. In this article, the effects of the gut microbiota on the functioning of the central nervous system are examined, with a focus on the symptoms of anxiety and depression. After examining how stress affects the autonomic, neuroendocrine, immunological, and neurotransmitter systems, modern gastrointestinal-based therapies stress the importance of the microbiome in the prevention and treatment of brain-based diseases including anxiety and depression.
Design and Development of Polymer-Based Optical Fiber Sensor for GAIT Analysis
Authors: Hema Mamidipaka , Suman Jami Venkata , Kumar Boddepalli Kiran , Haile Adisu
Published: February 2023

In the present scenario like COVID-19 pandemic, to maintain physical distance, the gait-based biometric is a must. Human gait identification is a very difficult process, but it is a suitable distance biometric that also gives good results at low resolution conditions even with face features that are not clear. This study describes the construction of a smart carpet that measures ground response force (GRF) and spatio-temporal gait parameters (STGP) using a polymer optical fiber sensor (POFS). The suggested carpet contains two light detection units for acquiring signals. Each unit obtains response from 10 nearby sensors. There are 20 intensity deviation sensors on a fiber. Light-emitting diodes (LED) are triggered successively, using the multiplexing approach that is being employed. Multiplexing is dependent on coupling among the LED and POFS sections. Results of walking experiments performed on the smart carpet suggested that certain parameters, including step length, stride length, cadence, and stance time, might be used to estimate the GRF and STGP. The results enable the detection of gait, including the swing phase, stance, stance length, and double supporting periods. The suggested carpet is dependable, reasonably priced equipment for gait acquisition in a variety of applications. Using the sensor data, gait recognition is performed using genetic algorithm (GA) and particle swarm optimization (PSO) technique. GA- and PSO-based gait template analyses are performed to extract the features with respect to the gait signals obtained from polymer optical gait sensors (POGS). The techniques used for classification of the obtained signals are random forest (RF) and support vector machine (SVM). The accuracy, sensitivity, and specificity results are obtained using SVM classifier and RF classifier. The results obtained using both classifiers are compared.
Also in Crayfish: How Phytase Inclusion Avoids Phytic Acid Effects on Hepatopancreas Enzymes of Redclaw Cherax quadricarinatus
Authors: Casaretto Matías E. , Stumpf Liane , Azcuy Rosendo L. , López Greco Laura S. , Colombatto Darío
Published: February 2023

This work aimed to evaluate the effects of dietary phytic acid on the enzymatic activities of the hepatopancreas of the redclaw crayfish, Cherax quadricarinatus. For this purpose, a completely randomized in vitro trial was conducted with three phytic acid levels (0.56, 1.68, and 2.80%) and three phytase doses (0, 250, and 500 PU/kg DM). Solubilized protein, reducing sugars, and soluble phosphorus showed significant responses to the interaction between phytic acid and phytase

p
<
0.001

. Only the main effects were detected on the released amino acids, in keeping with the main effects of alkaline protease activity, which are negatively affected by phytic acid

p
<
0.001

and improved by phytase inclusion

p
<
0.001

. Differences in released reducing sugars were attributed to a reduction in amylase activity by increased levels of phytic acid and not to cellulase activity, where only a negative trend of phytic acid was found

p

=

0.068

. Phytic acid depresses calcium availability, which would explain the decrease in amylase activity. A 500 PU/kg DM dose improved amino acid, reduced sugars, and phosphorus release. These in vitro results might have in vivo implications for the digestibility of proteins, minerals, and energy. Further investigations are required to determine the chelated calcium effect on redclaw amylase activity, molting, and survival.
Reverse Translation Identifies the Synergistic Role of Immune Checkpoint Blockade and IL15 to Enhance Immunotherapy of Ovarian Cancer
Authors: Felices Martin , Wesley Erin , Bendzick Laura E. , Kodal Behiye , Hopps Rachel , Grzywacz Bartosz , Hinderlie Peter , Miller Jeffrey S. , Geller Melissa A.
Published: February 2023

Immune checkpoint blockade (ICB) has changed the standard of care for many patients with cancer, yet no ICB is approved for ovarian cancer. We hypothesized that maintenance therapy with an IL15 “superagonist” (N-803) and ICB in combination could induce potent immune activation in ovarian cancer. Using flow cytometry, cytometry by time of flight analysis, and cytotoxicity assays, we analyzed patient samples from women with advanced epithelial ovarian cancer treated with N-803 for indications of PD-1/PD-L1 upregulation with this treatment. In addition, ICB and N-803 were evaluated in preclinical studies to determine the functional impact of combination therapy on natural killer (NK) cells in vitro and in vivo. We observed that N-803 stimulated initial NK-cell expansion in patient samples; however, proliferation was not sustained beyond 2 weeks despite continued treatment. This result was reverse translated back to the laboratory to determine the functional relevance of this finding. The addition of ICB with an antibody-dependent cellular cytotoxicity IgG1 antibody against PD-L1 (avelumab) or an IgG4 antibody against PD-1 (pembrolizumab) enhanced N-803 induced NK-cell function in vitro. Using models of human ovarian cancer and NK-cell adoptive transfer in mice, we showed enhanced antitumor control with N-803 and ICB, as well as a combination effect that enhanced NK-cell persistence and expansion in vivo. This work suggests that PD-1/PD-L1 blockade combined with IL15 signaling may overcome resistance to cytokine therapy in ovarian cancer.
Clinical Presentations, Management, and Factors Affecting Outcomes in Posterior Segment Open Globe Injuries: An Analysis of 2,360 Eyes
Authors: Dave Vivek Pravin , Das Anthony Vipin , Nayak Sameera , Panchal Bhavik , Kuhn Ferenc
Published: February 2023

Introduction: The aim of the study was to report the clinical presentations, management, and factors affecting the outcomes of posterior segment open globe injuries in 2,360 consecutive eyes. Methods: This was a retrospective, consecutive, non-comparative interventional case series. All cases with scleral and corneoscleral wounds presenting to these centers from January 2014 to January 2021 were included. The cases were defined according to the Birmingham Eye Traumatology Terminology system (BETTs) classification. The Ocular Trauma Score (OTS) was applied to the dataset. Results: Mean age of presentation was 36.63 ± 19.92 years (median 35 years). Penetrating trauma accounted for 70.92%, rupture for 18.6%, perforation for 4.60%, and IOFB in 5.88% eyes. In 76.60%, the location of injury involved zone 1 extending till zone 2, while in 23.40% it involved zone 2 and/or zone 3. Vision at presentation was logMAR 3.03 ± 0.99 and at the last visit was logMAR 2.47 ± 1.42 (p < 0.0001). Time interval between presentation to the treatment center and globe repair was 13.93 ± 19.56 h (median 7.60 h). Favorable functional outcomes were seen in 29.20% eyes and favorable anatomic outcomes in 66.90%. Decreasing age at presentation, penetrating injury instead of rupture or perforating injury, a higher OTS, absence of corneal involvement, absence of retinal detachment at presentation, and absence of concurrent orbital fracture were associated with a favorable functional outcome (>20/200). Final visual acuity in logMAR correlated with the OTS value calculated at presentation. Conclusions: In the absence of retinal detachment and orbital fracture, posterior open globe injuries typically have a favorable functional outcome. OTS correlated with the final visual acuity.
To Get the Most out of the Least: BRAF Molecular Evaluation in Melanoma Metastases on Cell Suspension from Fine Needle Aspiration Cytology Needle Rinses
Authors: Ronchi Andrea , Montella Marco , Carraturo Emma , Clery Eduardo , Zito Marino Federica , Amato Martina , Argenziano Giuseppe , Moscarella Elvira , Brancaccio Gabriella , Troiani Teresa , Alfano Pasquale , Alfano Roberto , Franco Renato , Cozzolino Immacolata
Published: February 2023

Introduction: Cytological samples from cutaneous melanoma (CM) metastases may be the only biomaterial available for diagnostic and predictive purpose in the clinical practice. BRAF evaluation from cytological samples actually implies the loss of one or more diagnostic smears, or the execution of one or more passes to obtain dedicated cytological samples. We tested BRAF molecular evaluation in CM metastases on cell suspension obtained from fine needle aspiration cytology (FNAC) needle rinses. Methods: Forty-two patients with lymph node enlargements and a previous CM were enrolled. Patients were submitted to FNAC, and direct smears and cell-block were prepared for diagnostic purpose. The needle was carefully flushed in a vial containing 350 μL of nuclease-free water and a cell suspension was obtained for BRAF molecular evaluation. Molecular evaluation was also performed on histological samples for statistics. Results: The series included 35 CM metastases and 7 reactive lymphadenopathies. Three cases resulted inadequate and adequacy was 92.9%. BRAF V600E/Ec mutations were found in 7 out of 32 (21.9%) CM metastases cases. BRAF mutations other than V600E/Ec were found in 2 out of 32 (6.25%) cases. Sensitivity, specificity, positive predictive value, and negative predictive value resulted 100%. Conclusion: BRAF molecular evaluation in CM metastases on cell suspension obtained from FNAC needle rinses is a time-sparing and accurate technique allowing to spare biomaterial in the clinical setting.
Compromised Adult Height in Females with Non-Classical Congenital Adrenal Hyperplasia Diagnosed in Childhood
Authors: Bello Rachel , Lazar Liora , Phillip Moshe , de Vries Liat
Published: February 2023

Introduction: Data on adult height (AHt) in individuals with non-classical congenital adrenal hyperplasia (NCCAH) are inconsistent. Methods: We conducted a retrospective study of 109 females diagnosed with NCCAH at age <18 years who reached AHt. We studied AHt compared to target height (THt) and the correlation of AHt with clinical parameters. Results: The mean age at diagnosis was 9.7 ± 4.4 years; the mean follow-up was 10.9 ± 6.3 years. Hydrocortisone treatment (11.0 ± 5.0 mg/m2) was initiated at age 9.7 ± 4.0 years. Bone age was more advanced in girls who presented with central precocious puberty or early puberty (CPP/EP) (n = 43) than with timely puberty. AHt-standard deviation score (SDS) was lower than Ht-SDS at diagnosis (−0.8 ± 1.0 vs. +0.2 ± 1.3; p < 0.001) and −0.3 SDS shorter than THt (p < 0.001). Height, weight, and body mass index-SDS at last visits were similar between patients treated with glucocorticoids (n = 92) and those never treated (n = 17). AHt was comparable between patients with timely puberty and with CPP/EP, with no difference between those treated or not by GnRH analogue. AHt was similar between patients who were fully pubertal (Tanner 5), pre-pubertal (Tanner 1), and pubertal (Tanner 2-4) at diagnosis (158.0 ± 7.6, 158.1 ± 6.1, and 157.5 ± 6.5, respectively; p = 0.9). AHt-SDS was correlated with THt (R = 0.67, p < 0.001) and Ht-SDS at diagnosis (R = 0.7, p < 0.001) but not with age at diagnosis (R = −0.05, p = 0.6), the extent of bone age advancement (R = −0.04, p = 0.72), glucocorticoid treatment duration (R = −0.11, p = 0.34), or dose (R = −0.04, p = 0.70). Conclusion: AHt of females diagnosed with NCCAH in childhood was lower than their THt. Glucocorticoid treatment duration and dose, pubertal status at diagnosis, and having CPP or EP were not correlated with AHt.
Clinicopathological Features of Gitelman Syndrome with Proteinuria and Renal Dysfunction
Authors: Zhang Lei , Peng Xiaoyan , Zhao Bingbin , Xia Peng , Wen Yubing , Ye Wei , Li Xuemei , Li Xuewang , Ye Wenling , Cheng Hong , Chen Limeng
Published: February 2023

Introduction: Gitelman syndrome (GS) is a rare renal tubular salt-wasting disorder. Besides kidney electrolyte loss, proteinuria and renal dysfunction were also observed. However, their incidence, risk factors, pathological features, and prognosis were unclear. Methods: We retrospectively reviewed 116 GS patients and analyzed their clinical, genetic, and pathological characteristics. We also systematically reviewed articles on GS with proteinuria and renal dysfunction. Results: Twenty-three GS patients had proteinuria (69.6%) and renal dysfunction (43.5%) with a mean age of 35.3 ± 13.2 years, and 65.2% were male. Compared to patients without proteinuria or renal dysfunction, these patients had elevated plasma angiotensin II level (440.2 ± 351.7 vs. 253.2 ± 187.4 pg/mL, p = 0.031) and three times higher incidence of diabetes. The renal pathology of nine biopsied patients indicated hypertrophy of the juxtaglomerular apparatus (100%), chronic tubulointerstitial changes (66.7%), intrarenal vascular changes (66.7%), and glomerulopathy (55.6%). More extensive renin staining was observed in patients with GS than in the control group with glomerular minor lesion (p < 0.001). During a median of 85 months (range, 11–205 months) of follow-up for 19 out of the 23 GS-renal patients, the renal function was generally stable, except one died of cancer and one developed end-stage renal disease because of concomitant membranous nephropathy and IgA nephropathy. Conclusion: Proteinuria and renal dysfunction were more common than expected and might indicate glomerulopathy and vascular lesions besides a tubulointerstitial injury in GS. Renal function may maintain stable with effective therapy in most cases.
One Heartbeat Away from a Prediction Model for Cardiovascular Diseases in Patients with Chronic Kidney Disease: A Systematic Review
Authors: Smit Leanne C.M. , Bots Michiel L. , van der Leeuw Joep , Damen Johanna A.A.G. , Blankestijn Peter J. , Verhaar Marianne C. , Vernooij Robin W.M.
Published: February 2023

Introduction: Patients with chronic kidney disease (CKD) have a high risk of cardiovascular disease (CVD). Prediction models, combining clinical and laboratory characteristics, are commonly used to estimate an individual’s CVD risk. However, these models are not specifically developed for patients with CKD and may therefore be less accurate. In this review, we aim to give an overview of CVD prognostic studies available, and their methodological quality, specifically for patients with CKD. Methods: MEDLINE was searched for papers reporting CVD prognostic studies in patients with CKD published between 2012 and 2021. Characteristics regarding patients, study design, outcome measurement, and prediction models were compared between included studies. The risk of bias of studies reporting on prognostic factors or the development/validation of a prediction model was assessed with, respectively, the QUIPS and PROBAST tool. Results: In total, 134 studies were included, of which 123 studies tested the incremental value of one or more predictors to existing models or common risk factors, while only 11 studies reported on the development or validation of a prediction model. Substantial heterogeneity in cohort and study characteristics, such as sample size, event rate, and definition of outcome measurements, was observed across studies. The most common predictors were age (87%), sex (75%), diabetes (70%), and estimated glomerular filtration rate (69%). Most of the studies on prognostic factors have methodological shortcomings, mostly due to a lack of reporting on clinical and methodological information. Of the 11 studies on prediction models, six developed and internally validated a model and four externally validated existing or developed models. Only one study on prognostic models showed a low risk of bias and high applicability. Conclusion: A large quantity of prognostic studies has been published, yet their usefulness remains unclear due to incomplete presentation, and lack of external validation of prognostic models. Our review can be used to select the most appropriate prognostic model depending on the patient population, outcome, and risk of bias. Future collaborative efforts should aim at improving existing models by externally validating them, evaluating the addition of new predictors, and assessment of the clinical impact. Registration: We have registered the protocol of our systematic review on PROSPERO (CRD42021228043).
Exploring the Relationship Between Efpeglenatide Dose and Cardiovascular Outcomes in Type 2 Diabetes: Insights From the AMPLITUDE-O Trial
Authors: Gerstein Hertzel C. , Li Zhuoru , Ramasundarahettige Chinthanie , Baek Seungjae , Branch Kelley R.H. , Del Prato Stefano , Lam Carolyn S.P. , Lopes Renato D. , Pratley Richard , Rosenstock Julio , Sattar Naveed
Published: February 2023

Background:

In the AMPLITUDE-O (Effect of Efpeglenatide on Cardiovascular Outcomes) cardiovascular outcomes trial, adding either 4 mg or 6 mg weekly of the glucagon-like peptide-1 receptor agonist efpeglenatide to usual care reduced major adverse cardiovascular events (MACE) in people with type 2 diabetes at high cardiovascular risk. Whether these benefits are dose related remains uncertain.

Methods:

Participants were randomly assigned in a 1:1:1 ratio to placebo, 4 mg or 6 mg of efpeglenatide. The effect of 6 mg versus placebo and of 4 mg versus placebo on MACE (a nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular or unknown causes) and on all the secondary composite cardiovascular and kidney outcomes was assessed. A dose-response relationship was assessed using the log-rank test and χ
2
statistic for trend.

Results:

During a median follow-up of 1.8 years, MACE occurred in 125 (9.2%) participants assigned to placebo, 84 (6.2%) participants assigned to 6 mg of efpeglenatide (hazard ratio [HR], 0.65 [95% CI, 0.5–0.86];
P
=0.0027), and 105 (7.7%) assigned to 4 mg of efpeglenatide (HR, 0.82 [95% CI, 0.63–1.06];
P
=0.14). Participants receiving high-dose efpeglenatide also experienced fewer secondary outcomes, including the composite of MACE, coronary revascularization, or hospitalization for unstable angina (HR, 0.73 for 6 mg,
P
=0.011; HR, 0.85 for 4 mg,
P
=0.17), a kidney composite outcome comprising sustained new macroalbuminuria, a ≥40% decline in estimated glomerular filtration rate or renal failure (HR, 0.63 for 6 mg,
P
<0.0001; HR, 0.73 for 4 mg,
P
=0.0009), MACE or any death (HR, 0.67 for 6 mg,
P
=0.0021; HR, 0.81 for 4 mg,
P
=0.08), a kidney function outcome comprising a sustained ≥40% decline in estimated glomerular filtration rate, renal failure, or death (HR, 0.61 for 6 mg,
P
=0.0072; HR, 0.97 for 4 mg,
P
=0.83), and the composite of MACE, any death, heart failure hospitalization, or the kidney function outcome (HR, 0.63 for 6 mg,
P
=0.0002; HR, 0.81 for 4 mg,
P
=0.067). A clear dose-response was noted for all primary and secondary outcomes (all
P
for trend ≤0.018).

Conclusions:

The graded salutary relationship between efpeglenatide dose and cardiovascular outcomes suggests that titrating efpeglenatide and potentially other glucagon-like peptide-1 receptor agonists to high doses may maximize their cardiovascular and renal benefits.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03496298.
‘Overcoming Modernity’, Overcoming What?: ‘Modernity’ in Wartime Japan and its Implication
Authors: Ichijo Atsuko
Published: February 2023

The Overcoming Modernity symposium that took place in wartime Japan (in summer 1942) gained notoriety in the postwar period, as a centrepiece of wartime propaganda justifying and legitimising Japanese military actions across Asia. While the published proceedings of the symposium were not as widely read as its postwar notoriety suggests, the phrase ‘overcoming modernity’ certainly captured the zeitgeist of the time in which ‘modernity’ was questioned, debated and contested. The efforts to examine ‘modernity’ in the first half of the twentieth century in Japan were led by a group of philosophers and intellectuals often referred to as the Kyoto School of philosophy because the school mainly drew its members from the Philosophy Department of the Imperial University of Kyoto, but their efforts were not made in isolation. Questioning of modernity in the form of western civilisation had been gathering pace in the West since the end of the nineteenth century, which the members of the Kyoto School were all well aware of. This naturally leads to a few questions: What did the Kyoto School mean by ‘modernity’ in this intellectual climate? Does their ‘modernity’ justify their claim to have overcome modernity? The paper explores what the wartime Japanese intellectuals including the members of the Kyoto School understood as modernity and what they suggested as a way of overcoming it by examining two sets of symposia that took place between 1941 and 1942: the Overcoming Modernity symposium (1942) and the Chūōkōron symposia (1941–42). This examination has implications for theoretical debates on modernity, in particular, on the strengths of the multiple modernities thesis.