bluuebunny/crossref_metadata_2025 huggingface dataset:
Niche differentiation among facultative filter feeders: Insights from invasive Ponto-Caspian mysids
Authors: Borza Péter , Rani Varsha , Vad Csaba F
Published: July 2023

The degree of dietary specialization has a fundamental impact on the ecological function and interactions of suspension feeders. While niche differentiation by food particle size is common among obligate suspension feeders, its role is not evident in facultative ones. In this study, we aimed at providing new insights on the matter by focusing on sympatric mysid species. As mysids use different mechanisms for raptorial and filter-feeding, they represent a more adequate model system than for example, the more extensively studied copepods. We made morphological measurements on the 4 coexisting invasive Ponto-Caspian mysid species to determine the areas and mesh sizes of their filters. We also quantified their clearance rates on the microalga Cryptomonas sp. in a laboratory experiment to reveal how morphological differences manifest in their overall filtering capacity. We found relatively small but consistent differences in the primary filter area among the species, indicating that morphological constraints due to the enclosed position of the setae might limit the possibility for differentiation. The primary filter mesh sizes were small in all 4 species (0.69–2.73 μm) with moderate but consistent intraspecific differences, suggesting that the benefit of being able to capture small particles might outweigh the pressure for differentiation. The observed clearance rates were in accordance with the morphological characteristics of the species, highlighting that auxiliary filters (present in one of the species, Limnomysis benedeni) are needed to increase filtering capacity considerably. Our study confirmed that food particle size can contribute to the niche differentiation of facultative filter feeders, but also indicated that they can tolerate a higher overlap than obligate ones. The observed differences were related to the habitat preferences and predatory potentials of the species, suggesting that complementarity among the different niche axes might further facilitate their coexistence.
Vegetarian and vegan diets: benefits and drawbacks
Authors: Wang Tian , Masedunskas Andrius , Willett Walter C , Fontana Luigi
Published: July 2023

Plant-based diets have become increasingly popular thanks to their purported health benefits and more recently for their positive environmental impact. Prospective studies suggest that consuming vegetarian diets is associated with a reduced risk of developing cardiovascular disease (CVD), diabetes, hypertension, dementia, and cancer. Data from randomized clinical trials have confirmed a protective effect of vegetarian diets for the prevention of diabetes and reductions in weight, blood pressure, glycosylated haemoglobin and low-density lipoprotein cholesterol, but to date, no data are available for cardiovascular event rates and cognitive impairment, and there are very limited data for cancer. Moreover, not all plant-based foods are equally healthy. Unhealthy vegetarian diets poor in specific nutrients (vitamin B12, iron, zinc, and calcium) and/or rich in highly processed and refined foods increase morbidity and mortality. Further mechanistic studies are desirable to understand whether the advantages of healthy, minimally processed vegetarian diets represent an all-or-nothing phenomenon and whether consuming primarily plant-based diets containing small quantities of animal products (e.g. pesco-vegetarian or Mediterranean diets) has beneficial, detrimental, or neutral effects on cardiometabolic health outcomes. Further, mechanistic studies are warranted to enhance our understanding about healthy plant-based food patterns and the biological mechanisms linking dietary factors, CVD, and other metabolic diseases.
First molecular detection of Entamoeba gingivalis subtypes in individuals from Turkey
Authors: Örsten Serra , Şahin Cem , Yılmaz Engin , Akyön Yakut
Published: July 2023

Entamoeba gingivalis is a parasitic protozoan that colonizes the human oral cavity and there are two subtypes (ST1 and ST2) that have been identified to date. However, there are no reports on the molecular detection or characterization of E. gingivalis in Turkey. The objective of this study was to detect the presence of E. gingivalis in Turkish healthy individuals and those with periodontal disease and to subtype the isolates using molecular techniques. Samples from the oral cavity of 94 individuals were taken and the presence of E. gingivalis was determined by PCR using primers for SsrRNA and the amplicons were then confirmed by DNA sequencing. Each participant completed a questionnaire that included demographic data, habits and lifestyle, as well as health status. The presence of E. gingivalis was detected in a total of 19 samples (11 patients and eight healthy individuals). Molecular characterization determined that 12 samples belonged to ST1 and seven samples belonged to ST2. The presence of E. gingivalis was higher in patients with periodontal disease than in healthy individuals, and this association was statistically significant (P < .05). This study constitutes the first report of molecular detection and subtyping of E. gingivalis in Turkey.
Safety and Monitoring of Inflammatory Bowel Disease Advanced Therapies
Authors: Bhat Shubha , Click Benjamin , Regueiro Miguel
Published: July 2023

The recent approval of new medications with novel mechanisms of action and emergence of updated safety information for existing therapies has changed the treatment landscape of inflammatory bowel disease (IBD). These advances led to unique adverse effect profiles and identification of new safety signals, resulting in the evolution of the safety, monitoring, and positioning of IBD therapies. In this updated review, we (1) examine the existing and updated safety data of monoclonal antibodies and small molecules for IBD, with a focus on recently Food and Drug Administration (FDA)-approved therapies, and (2) propose risk stratification and assessment considerations prior to and during IBD treatment.
Algebraic Automatic Continued Fractions in Characteristic 2
Authors: Hu Yining
Published: July 2023

We present two families of automatic sequences that define algebraic continued fractions in characteristic $2$. The period-doubling sequence belongs to the first family $\mathcal {P}$, and its sum modulo $2$, the Thue–Morse sequence, belongs to the second family $\mathcal {G}$. The family $\mathcal {G}$ contains all the iterated sums of sequences from the $\mathcal {P}$ and more.
Aiding War: Foreign Aid and the Intensity of Violent Armed Conflict
Authors: Findley Michael , Young Joseph K , Strandow Daniel , Cat Olgahan
Published: July 2023

Does foreign aid reduce violence during ongoing wars? In the policy community, there has been growing optimism about the prospect for aid to improve conflict-affected and fragile areas. We investigate whether foreign aid decreases, or even increases, violence during ongoing armed conflict. We advance a theoretical argument that concentrated foreign assistance allocated during ongoing armed conflicts increases military fatalities but decreases civilian fatalities. Using geographically coded data on all sub-Saharan African countries in conflict between 1989 and 2008, within a matching frontier design and supplemented by instrumental variable analysis, we find strong substantive and statistical support for our expectations about military conflict intensity though less support for the expectations about civilian fatalities. The paper provides novel insights about the effects of concentrated aid on military versus civilian conflict intensity, characterizes the effects at a sub-national level, and expands the spatial-temporal period of the analysis. We also probe the plausibility of the causal mechanism using interview evidence drawn from ex-commanders of the Lord’s Resistance Army and generals of the Ugandan People’s Defence Forces in northern Uganda. The paper offers both academic and policy insights, including that foreign aid allocated during ongoing wars may be more problematic than it is helpful.
Pathogenic and transmissional potentials of a Chromobacterium haemolyticum isolate from a hydroponic farm
Authors: Zwe Ye Htut , Li Dan
Published: July 2023

Aims

This study aims to investigate the in vitro pathogenicity of Chromobacterium haemolyticum strain WI5 toward the intestinal tract, its resistance to water treatments, and its potential for foodborne transmission through leafy greens produced in hydroponic systems.

Methods and results

C. haemolyticum WI5 caused cytopathic effects in human colon cells HCT116 and exhibited an 8.2-fold higher cell attachment compared to Salmonella serotype Typhimurium. It showed comparable resistance to sodium hypochlorite (NaOCl) and ultraviolet (UV) treatments as Escherichia coli O157: H7 and Pseudomonas aeruginosa but was more susceptible to desiccation. On lettuce, C. haemolyticum WI5 failed to persist, with counts decreasing below the detection limit (≥4 log reductions) after 3 and 2 days at 4 and 25°C, respectively.

Conclusions

C. haemolyticum WI5 demonstrated considerable virulence features and high in vitro pathogenicity toward the intestinal tract. NaOCl and UV treatments were effective in disinfecting C. haemolyticum in water. Due to its high susceptibility to desiccation and poor survivability on lettuce, the foodborne transmission potential of C. haemolyticum is considered limited.
Evaluation of the Roche MagNA Pure 96 nucleic acid extraction platform for the SPF10 line probe assay system
Authors: Peng Siying , Yin Jian , Liu Yiwei , Bi Zhaofeng , Wu Ting , Qiao Youlin
Published: July 2023

Objective

To evaluate the MagNA Pure 96 (MP96) nucleic acid extraction system as an alternative for cervical specimen processing for human papillomavirus (HPV) genotyping detection by reverse hybridization line probe assay (LiPA-25), compared to the well-established extraction system MagNA Pure LC 2.0 (MPLC).

Methods and results

A total of 200 cervical samples preserved in ThinPrepCyt® solution were extracted by MP96 and MPLC, respectively, and then purified nucleic acids were amplified using the SPF10 PCR primer set. Amplification products were subjected to SPF10-DNA enzyme immunoassay (DEIA) and LiPA-25. The concordance between different extraction methods in this study was reflected in the comparison of the results of the DEIA and LiPA-25. Agreement of HPV-positive results (DEIA) was 97.5% (Kappa = 0.932). Pair-wise analyses of either HPV grouping (any HPV genotypes, any high-risk HPV genotypes, any low-risk HPV genotypes, any nonavalent vaccine-targeted HPV, and any non-vaccine-targeted oncogenic HPV genotypes) identified >95% agreement (all Kappa > 0.900). For the two extraction methods, there was no statistical difference (chi-square test: P = 0.690) for single versus multiple genotypes, and concordant, compatible, and discordant genotypes were observed in 87.0%, 9.5%, and 3.5% of 200 samples, respectively.

Conclusion

HPV genotyping results of the MPLC system and the MP96 system showed a high degree of concordance. Combined with the advantages of high-throughput and anti-contamination of MP96, the MP96 extraction system could be more suitable for the testing of samples in future studies.
Inferring cancer disease response from radiology reports using large language models with data augmentation and prompting
Authors: Tan Ryan Shea Ying Cong , Lin Qian , Low Guat Hwa , Lin Ruixi , Goh Tzer Chew , Chang Christopher Chu En , Lee Fung Fung , Chan Wei Yin , Tan Wei Chong , Tey Han Jieh , Leong Fun Loon , Tan Hong Qi , Nei Wen Long , Chay Wen Yee , Tai David Wai Meng , Lai Gillianne Geet Yi , Cheng Lionel Tim-Ee , Wong Fuh Yong , Chua Matthew Chin Heng , Chua Melvin Lee Kiang , Tan Daniel Shao Weng , Thng Choon Hua , Tan Iain Bee Huat , Ng Hwee Tou
Published: July 2023

Objective

To assess large language models on their ability to accurately infer cancer disease response from free-text radiology reports.

Materials and Methods

We assembled 10 602 computed tomography reports from cancer patients seen at a single institution. All reports were classified into: no evidence of disease, partial response, stable disease, or progressive disease. We applied transformer models, a bidirectional long short-term memory model, a convolutional neural network model, and conventional machine learning methods to this task. Data augmentation using sentence permutation with consistency loss as well as prompt-based fine-tuning were used on the best-performing models. Models were validated on a hold-out test set and an external validation set based on Response Evaluation Criteria in Solid Tumors (RECIST) classifications.

Results

The best-performing model was the GatorTron transformer which achieved an accuracy of 0.8916 on the test set and 0.8919 on the RECIST validation set. Data augmentation further improved the accuracy to 0.8976. Prompt-based fine-tuning did not further improve accuracy but was able to reduce the number of training reports to 500 while still achieving good performance.

Discussion

These models could be used by researchers to derive progression-free survival in large datasets. It may also serve as a decision support tool by providing clinicians an automated second opinion of disease response.

Conclusions

Large clinical language models demonstrate potential to infer cancer disease response from radiology reports at scale. Data augmentation techniques are useful to further improve performance. Prompt-based fine-tuning can significantly reduce the size of the training dataset.
Beta-Binomial Statistical Model for Validation Studies of Analytes with a Binary Response
Authors: LaBudde Robert A , Wehling Paul
Published: July 2023

Background

The probability of detection (POD) model has had widespread application for statistically analyzing single and multiple collaborator validations studies with binary outcome data for a wide range of analytes over the last decade.

Objective

The POD model is placed on a firm theoretical foundation, and extended to a more generalized beta-binomial model.

Methods

The POD model is revisited and embedded in the beta-binomial model. This generalization includes collaborator reproducibility as a specific parameter. The new model includes only two distributional parameters: the overall across-collaborator probability of detection (LPOD) and the intraclass correlation of collaborators (ICC), measuring irreproducibility. Differences between methods are measured by the difference in LPOD values, denoted dLPOD.

Results

Accurate statistical estimators and confidence intervals are provided with validation by simulation. This new beta-binomial model will be applicable to a full range of candidate methods giving binary qualitative results, including microbiological, toxin, allergen, biothreat, and botanical analytes.

Conclusions

The new beta-binomial model provides easy equivalence tests to show the study clearly demonstrates (with 95% confidence) that the method differences and collaborator reproducibility are acceptable.

Highlights

The validation system for qualitative binary methods using probability of detection (POD) of an analyte as the parameter of interest has been modified and further validated.
Topology optimization via machine learning and deep learning: a review
Authors: Shin Seungyeon , Shin Dongju , Kang Namwoo
Published: July 2023

Topology optimization (TO) is a method of deriving an optimal design that satisfies a given load and boundary conditions within a design domain. This method enables effective design without initial design, but has been limited in use due to high computational costs. At the same time, machine learning (ML) methodology including deep learning has made great progress in the 21st century, and accordingly, many studies have been conducted to enable effective and rapid optimization by applying ML to TO. Therefore, this study reviews and analyzes previous research on ML-based TO (MLTO). Two different perspectives of MLTO are used to review studies: (i) TO and (ii) ML perspectives. The TO perspective addresses “why” to use ML for TO, while the ML perspective addresses “how” to apply ML to TO. In addition, the limitations of current MLTO research and future research directions are examined.
Micrococcus spp. as a promising source for drug discovery: A review
Authors: Tizabi Daniela , Hill Russell T
Published: July 2023

Historically, bacteria of the phylum, Actinobacteria have been a very prominent source of bioactive compounds for drug discovery. Among the actinobacterial genera, Micrococcus has not generally been prioritized in the search for novel drugs. The bacteria in this genus are known to have very small genomes (generally < 3 Mb). Actinobacteria with small genomes seldom contain the well-characterized biosynthetic gene clusters such as those encoding polyketide synthases and nonribosomal peptide synthetases that current genome mining algorithms are optimized to detect. Nevertheless, there are many reports of substantial pharmaceutically relevant bioactivity of Micrococcus extracts. On the other hand, there are remarkably few descriptions of fully characterized and structurally elucidated bioactive compounds from Micrococcus spp. This review provides a comprehensive summary of the bioactivity of Micrococcus spp. that encompasses antibacterial, antifungal, cytotoxic, antioxidant, and anti-inflammatory activities. This review uncovers the considerable biosynthetic potential of this genus and highlights the need for a re-examination of these bioactive strains, with a particular emphasis on marine isolates, because of their potent bioactivity and high potential for encoding unique molecular scaffolds.
Policy options to facilitate cancer genomic variant data sharing: outcomes of a modified policy Delphi
Authors: Robinson Jill O , Daoud Amira , Geary Janis , Rahimzadeh Vasiliki , Bollinger Juli , Guerrini Christi J , Cook-Deegan Robert , McGuire Amy L , Majumder Mary A
Published: July 2023

Sharing cancer gene variant and relevant clinical data could accelerate progress in cancer genomics. However, data sharing is currently impeded by issues related to financial sustainability, equity, incentives, privacy and security, and data quality. Evidence-based policy options to facilitate data sharing in these domains, and ultimately improve interpretation of cancer-associated genomic variants, are therefore needed. We conducted a modified policy Delphi with expert stakeholders that involved generating, evaluating, and ranking potential policy options to address these issues, with a focus on the US context. We found policy options in the financial sustainability domain were highly ranked, particularly stable funding for trusted entities. However, some Delphi panelists noted that the culture of public research funding has favored short-term grants. Panelists favored policy options focused on action by funders, which had the highest overall total scores that combined effectiveness and feasibility ratings and priority ranking within domains. Panelists also endorsed some policy options connected to actors such as journals, but they were more skeptical of policy options connected to legislative actors and data resources. These findings are critical inputs for policy makers as they consider policies to enable sharing of cancer gene variant data to improve health.
Estimating default probabilities for no- and low-default portfolios: parameter specification via floor constraints
Authors: Blümke Oliver
Published: July 2023

For low- and no-default portfolios, financial institutions are confronted with the problem to estimate default probabilities for credit ratings for which no default was observed. The Bayesian approach offers a solution but brings the problem of the parameter assignment of the prior distribution. Sequential Bayesian updating allows to settle the question of the location parameter or mean of the prior distribution. This article proposes to use floor constraints to determine the scale or standard deviation parameter of the prior distribution. The floor constraint can also be used to determine the free parameter γ in the Pluto–Tasche approach.
Ageing and quenching through the Ageing Diagram – II. Physical characterization of galaxies
Authors: Corcho-Caballero Pablo , Ascasibar Yago , Cortese Luca , Sánchez Sebastián F , López-Sánchez Ángel R , Fraser-McKelvie Amelia , Zafar Tayyaba
Published: July 2023

The connection between quenching mechanisms, which rapidly turn star-forming systems into quiescent, and the properties of the galaxy population remains difficult to discern. In this work we investigate the physical properties of MaNGA and SAMI galaxies at different stages of their star formation history. Specifically, we compare galaxies with signatures of recent quenching (Quenched) – $\rm H \, \alpha$ in absorption and low Dn(4000) – with the rest of the low star-forming and active population (Retired and Ageing, respectively). The analysis is performed in terms of characteristics such as the total stellar mass, half-light radius, velocity-to-dispersion ratio, metallicity, and environment. We find that the Ageing population comprises a heterogeneous mixture of galaxies, preferentially late-type systems, with diverse physical properties. Retired galaxies, formerly Ageing or Quenched systems, are dominated by early-type high-mass galaxies found both at low and dense environments. Most importantly, we find that recently quenched galaxies are consistent with a population of compact low-mass satellite systems, with higher metallicities than their Ageing analogues. We argue that this is compatible with being quenched after undergoing a star-burst phase induced by environmental processes (e.g. ram pressure). However, we also detect a non-negligible fraction of field central galaxies likely quenched by internal processes. This study highlights that, in order to constrain the mechanisms driving galaxy evolution, it is crucial to distinguish between old (Retired) and recently quenched galaxies, thus requiring at least two estimates of the specific star formation rate over different time-scales.
Detecting the H i power spectrum in the post-reionization Universe with SKA-Low
Authors: Chen Zhaoting , Chapman Emma , Wolz Laura , Mazumder Aishrila
Published: July 2023

We present a survey strategy to detect the neutral hydrogen (H i) power spectrum at 5 < z < 6 using the SKA-Low radio telescope in presence of foregrounds and instrumental effects. We simulate observations of the inherently weak H i signal post-reionization with varying levels of noise and contamination with foreground amplitudes equivalent to residuals after sky model subtraction. We find that blind signal separation methods on imaged data are required in order to recover the H i signal at large cosmological scales. Comparing different methods of foreground cleaning, we find that Gaussian Process Regression (GPR) performs better than Principle Component Analysis (PCA), with the key difference being that GPR uses smooth kernels for the total data covariance. The integration time of one field needs to be larger than ∼250 h to provide large enough signal-to-noise ratio (SNR) to accurately model the data covariance for foreground cleaning. Images within the primary beam field-of-view give measurements of the H i power spectrum at scales $k\sim 0.02\, {\rm Mpc^{-1}}-0.3\, {\rm Mpc^{-1} }$ with SNR ∼2–5 in Δ[log(k/Mpc−1)] = 0.25 bins assuming an integration time of 600 h. Systematic effects, which introduce small-scale fluctuations across frequency channels, need to be ≲ 5 × 10−5 to enable unbiased measurements outside the foreground wedge. Our results provide an important validation towards using the SKA-Low array for measuring the H i power spectrum in the post-reionization Universe.
SCOTCH − search for clandestine optically thick compact H iis
Authors: Patel A L , Urquhart J S , Yang A Y , Moore T J T , Menten K M , Thompson M A , Hoare M G , Irabor T , Breen S L , Smith M D
Published: July 2023

This study uses archival high-frequency continuum data to expand the search for Hypercompact H ii regions and determine the conditions at which they appear, as this stage high mass star formation is short-lived and rare. We use 23 GHz continuum data taken towards methanol masers, which are an excellent signpost for very young embedded high-mass protostars. We have searched for high-frequency, optically thick radio sources to identify HC H ii region candidates. The data cover 128 fields that include 141 methanol masers identified by the Methanol Multibeam (MMB) survey. We have detected 68 high-frequency radio sources and conducted a multiwavelength analysis to determine their nature. This has identified 49 H ii regions, 47 of which are embedded in dense clumps fourteen of which do not have a 5 GHz radio counterpart. We have identified 13 methanol maser sites that are coincident with radio sources that have a steep positive spectral index. The majority of these are not detected in the mid-infrared and have been classified as protostellar or young stellar objects in the literature and we therefore consider to be good HC H ii region candidates, however, further work and higher resolution data are needed to confirm these candidates.
Analysis of the possible satellite contamination in LAMOST-MRS spectra
Authors: Kovalev Mikhail , Hainaut Olivier R , Chen Xuefei , Han Zhanwen
Published: July 2023

We present the detection of false positive double-lined spectroscopic binaries candidates using medium-resolution survey spectra from the one time-domain field of Large Sky Area Multi-Object Fibre Spectroscopic Telescope data release 10. The secondary component in all these binaries has near zero radial velocity and solar-like spectral lines. Highly likely this is light from the semitransparent clouds illuminated by the full Moon. However we also suspect that partially this contamination can be caused by a solar light reflected from the surface of low-orbital artificial satellites launched in the beginning of 2022. We found several possible contaminant candidates using archival orbital data. We propose measures to reduce risk of such contamination for the future observations and methods to find it in archived ones.
The Weighted Toxicity Score: Confirmation of a Simple Metric to Communicate Toxicity in Randomized Trials of Systemic Cancer Therapy
Authors: Jordan Jacob , Maki Robert G
Published: July 2023

Introduction

FDA’s Project Optimus was developed in part to better identify appropriate dose and schedule of cancer therapeutics. The tabular method to summarize patients’ maximum toxicity in a clinical trial does not allow for ready comparison to the treatment’s benefit. In this manuscript, we apply a simple tool, the weighted toxicity score (WTS), to trials involving lung cancer immunotherapy and chemotherapy, as well as those cited in a recent publication as examples of trials that represent successful reduction of the appropriate dose of anti-cancer agents.

Methods

PubMed was queried for randomized controlled trials of therapy involving immune checkpoint inhibitors in lung cancer. Trial data from studies highlighting initial success with dose adjustments after FDA approval also were assembled and analyzed according to the WTS procedure described previously, compared to clinical outcomes data.

Results

The WTS provided, with the clinical outcome(s), a data pair that leads to easy interpretation of the expected benefit versus relative toxicity of studies involving immunotherapy or chemoimmunotherapy in lung cancers. The WTS was consistent with the conclusions of the primary studies, helping to quantitate the toxicity difference between treatments in a previously unavailable way.

Conclusion

The WTS provides a tool to show the cost in toxicity of therapy in a randomized clinical trial, with applicability to studies involving chemotherapy, immunotherapy, or kinase-directed therapy. Inclusion of a running tally of WTS during conduct of a trial could serve as one means to adjust dosing or to provide feedback during data safety monitoring of a clinical trial.
Denosumab in Giant Cell Rich Tumors of Bone: An Open-Label Multicenter Phase II Study
Authors: Lipplaa Astrid , Schreuder Willem H , Pichardo Sarina E C , Gelderblom Hans
Published: July 2023

Background

Since giant cell tumors of bone (GCTB) and other giant cell rich tumors of bone (GCRTB) share the histological presence of osteoclastic giant cells and expression of RANK/RANKL, we hypothesized that GCRTB will respond similarly to denosumab as GCTB. The primary objective of this study was to determine the efficacy of denosumab in patients with GCRTB that have recurred or require morbid surgery.

Methods

In this open-label, multicenter, phase II trial, patients with GCRTB were included (June 2018-March 2020). Recruitment was stopped because of low accrual. Patients received denosumab (120 mg) subcutaneously (SC) on day 1 of every 4-week cycle with a loading dose of 120 mg SC on days 8 and 15.

Results

Three patients were enrolled. One withdrew consent before start of study. The remaining patients had central giant cell granuloma of the jawbone (CGCG). Median treatment duration was 15 cycles (range 12-18). In both subjects, improvement in ossification of lesions was seen. Median follow-up was 28.5 months (range 20-37). One patient developed a recurrence for which surgery was performed.

Conclusion

Due to critical emerging real-world data of denosumab in GCRTBs, the study was prematurely stopped and not supportive of use of denosumab for this indication. (ClinicalTrials.gov Identifier: NCT03605199).
National digital health legislation: lessons and recommendations
Authors: Venkatasubramanian Akarsh , Patnaik Amar
Published: July 2023

All Member States of the United Nations have committed to achieve the UN Sustainable Development Goals (SDGs) and Universal Health Coverage (UHC), but several policy and system challenges remain unaddressed. Technology innovation and digital health have the potential to find equitable, sustainable and rights-based solutions to many of these issues, but must be coupled with effective and appropriate national legislation. In the backdrop of today's global digital health landscape, this manuscript explores the urgent need for the national legislation on digital health and recommends a way forward for legislators to meaningfully address this need. It also presents direction for global and national stakeholders to coordinate their efforts towards supporting countries to enable meaningful digital health transformations. The recommendations below are informed by perspectives from international organizations, national parliaments, policy think tanks and civil society.
Establishment and validation of a calibration curve for dicentric chromosome induced by 6MV X-ray
Authors: Kosarnia Morteza , Bahreyni-Toossi Mohammad-Taghi , Gholamhosseinian Hamid , Dolat Elham , Fakour-Mollaee Parisa , Azimian Hosein
Published: July 2023

Radiation during radiotherapy and nuclear accidents is currently one of the biggest concerns for the international community. Biological dosimetry examines the amount of damage caused by radiation at the cellular level by quantifying a radiation biomarker. In particular, the dicentric chromosome assay is a biodosimetric technique that can quantify radiation damage by correlating radiation dose exposure with the frequency of dicentric chromosomes in the peripheral lymphocytes extracted from exposed individuals. This study aims to present of the reference dose–response calibration curve for biodosimetry laboratory of Mashhad University of Medical Sciences (north-east of Iran). In all, 40 samples of peripheral blood from four healthy volunteers were irradiated at doses of 0–5 Gray in a customised water phantom using a 6 MV X-rays at dose rate of 2 Gy/min from a linear accelerator. The irradiated samples were cultured and analysed according to the International Atomic Energy Agency Cytogenetic Dosimetry Protocol (2011) with some modifications. Linear-quadratic model curve fitting and further statistical analysis were done using Chromosome Aberration Calculation Software Version 2.0 and Dose Estimate (Version 5.2). The curve equation obtained was ${Y}_{dic}=0.0533{D}^2+0.0231D+0.0001$ and was in the range of other studies. Validation of the calibration curve was done by estimating the dose of blind samples.
Effects of Substance Use and Antisocial Personality on Neuroimaging-Based Machine Learning Prediction of Schizophrenia
Authors: Taipale Matias , Tiihonen Jari , Korhonen Juuso , Popovic David , Vaurio Olli , Lähteenvuo Markku , Lieslehto Johannes
Published: July 2023

Background and hypothesis

Neuroimaging-based machine learning (ML) algorithms have the potential to aid the clinical diagnosis of schizophrenia. However, literature on the effect of prevalent comorbidities such as substance use disorder (SUD) and antisocial personality (ASPD) on these models’ performance has remained unexplored. We investigated whether the presence of SUD or ASPD affects the performance of neuroimaging-based ML models trained to discern patients with schizophrenia (SCH) from controls.

Study design

We trained an ML model on structural MRI data from public datasets to distinguish between SCH and controls (SCH = 347, controls = 341). We then investigated the model’s performance in two independent samples of individuals undergoing forensic psychiatric examination: sample 1 was used for sensitivity analysis to discern ASPD (N = 52) from SCH (N = 66), and sample 2 was used for specificity analysis to discern ASPD (N = 26) from controls (N = 25). Both samples included individuals with SUD.

Study results

In sample 1, 94.4% of SCH with comorbid ASPD and SUD were classified as SCH, followed by patients with SCH + SUD (78.8% classified as SCH) and patients with SCH (60.0% classified as SCH). The model failed to discern SCH without comorbidities from ASPD + SUD (AUC = 0.562, 95%CI = 0.400–0.723). In sample 2, the model’s specificity to predict controls was 84.0%. In both samples, about half of the ASPD + SUD were misclassified as SCH. Data-driven functional characterization revealed associations between the classification as SCH and cognition-related brain regions.

Conclusion

Altogether, ASPD and SUD appear to have effects on ML prediction performance, which potentially results from converging cognition-related brain abnormalities between SCH, ASPD, and SUD.
Increased hippocampal efficiency is associated with greater headache frequency in adolescents with chronic headache
Authors: Cobos Karen L , Long Xiangyu , Lebel Catherine , Rasic Nivez , Noel Melanie , Miller Jillian Vinall
Published: July 2023

Adults with chronic headache have altered brain hippocampal efficiency networks. Less is known about the mechanisms underlying chronic headache in youth. Twenty-nine youth with chronic headache (10–18 years), and twenty-nine healthy, age- and sex-matched controls tracked their headache attacks daily for one-month period. Following this, they underwent a resting state functional magnetic resonance imaging (rs-fMRI) scan and self-reported on their pubertal status, PTSD, anxiety, and depression symptoms. Graph-based topological analyses of brain networks, rendering hippocampal efficiency values were performed. T-tests were used to compare hippocampal efficiency metrics between patients and controls. Linear regression was used to examine significant hippocampal efficiency metrics in relation to headache frequency in patients, controlling for age, sex, PTSD, pubertal status, anxiety, and depression symptoms.

Patients had higher right hippocampal global efficiency, shorter right hippocampal path length, and higher right hippocampal clustering coefficient compared to controls (P < 0.05). Higher right hippocampal global efficiency, shorter right hippocampal path length, and higher right hippocampal clustering coefficients were positively associated with greater headache frequency (P < 0.05). The hippocampus is largely involved in memory formation and retrieval, and this data provides additional support for previous findings demonstrating the importance of the hippocampus and pain memories for the chronification of pain.
Comparison of the Analgesic Efficacy between Arthroscopically Placed Continuous Suprascapular Nerve Block and Ultrasound-guided Continuous Superior Trunk Block: A Double-blinded Randomized Controlled Trial
Authors: Kim Ha-Jung , Koh Kyoung Hwan , Park Ji In , Kim Yeon Ju , Kim Min-Ju , Kim Hyojune , Kim Hyungtae , Ro Young-Jin , Koh Won Uk
Published: July 2023

Background

Single-shot suprascapular nerve block and superior trunk block have been reported to provide a noninferior analgesic effect after shoulder surgery with a lesser incidence of hemidiaphragmatic paresis compared with interscalene brachial plexus block. This study hypothesized that continuous suprascapular nerve block provides noninferior analgesia with minimal effects on diaphragmatic movement compared with continuous superior trunk block in patients undergoing arthroscopic shoulder surgery.

Methods

100 patients were randomized undergoing arthroscopic shoulder surgery between December 2020 and October 2021 into continuous suprascapular nerve block and continuous superior trunk block groups. Before the surgery, patients received either a single-shot superior trunk block or subomohyoid suprascapular nerve block. Thereafter, a superior trunk catheter was inserted by anesthesiologists in patients in the continuous superior trunk block group, and a posterior suprascapular nerve catheter was inserted with arthroscopic assistance during the surgery by surgeon in the continuous suprascapular nerve block group. The primary outcome was the postoperative pain score at postoperative 24 h, and the incidence of hemidiaphragmatic paresis was also compared.

Results

Overall, 98 patients were included in the final analysis. The worst and resting pain scores at postoperative 24 h in the continuous suprascapular nerve block group were inferior compared with those in the continuous superior trunk block group in the test with a noninferiority margin of 1 (worst pain score: mean difference, 0.9; 95% CI, 0.1 to 1.7; resting pain score: mean difference, 0.5; 95% CI, 0.0 to 1.0). However, the continuous suprascapular nerve block group had a significantly lower incidence of hemidiaphragmatic paresis at postoperative 24 h than the continuous superior trunk block group.

Conclusions

Continuous suprascapular nerve block provides statistically inferior analgesia compared to the continuous superior trunk block; however, the continuous suprascapular nerve block had a minimal effect on the phrenic nerve function.

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Blood Pressure Management Goals in Critically Ill Aneurysmal Subarachnoid Hemorrhage Patients in Australia and New Zealand
Authors: Betteridge Toby , Finnis Mark , Cohen Jeremy , Delaney Anthony , Young Paul , Udy Andrew ,   for the PROMOTE-SAH Investigators
Published: July 2023

Introduction:

Blood pressure (BP) management is common in patients with aneurysmal subarachnoid hemorrhage (SAH) admitted to an intensive care unit. However, the practice patterns of BP management (timing, dose, and duration) have not been studied locally.

Methods:

This post hoc analysis explored BP management goals (defined as the setting of a minimum systolic BP target or application of induced hypertension) in patients enrolled into the PROMOTE-SAH study in eleven neurosurgical centers in Australia and New Zealand. The primary outcome was ‘dead or disabled’ (modified Rankin Score ≥4) at 6 months, with the hypothesis being that setting BP management goals would be associated with improved outcomes.

Results:

BP management goals were recorded in 266 of 357 (75%) patients, of which 149 were recorded as receiving induced hypertension for delayed cerebral ischemia (DCI) or vasospasm on 738 (19%) study days. In patients with a minimum systolic BP goal recorded (on 2067 d), the indication for the BP management goal was vasospasm or DCI on 651 (32%) days; no indication for BP management goals was documented on 1416 (69%) days. Crude analysis demonstrated an association between setting BP management goals and reduced death or disability (P=0.03), but this association was not significant after adjustment for the presence of DCI or vasospasm and clustered by the site.

Conclusions:

BP management goals are commonly ‘prescribed’ to aSAH patients admitted to an intensive care unit in Australia and New Zealand, but BP management goal setting was not associated with improved outcomes in the adjusted analysis.
Posteromedial Surgical Approach for Fixation of Haraguchi Type 2B Posterior Malleolar Fracture
Authors: Solasz Sara , Ganta Abhishek , Konda Sanjit R.
Published: July 2023

A case of a 26-year-old man with a displaced medial malleolus fracture with extension into the posteromedial aspect of the posterior malleolus is presented. A CT scan of the ankle is obtained demonstrating a Haraguchi type 2B posterior malleolus fracture with a posteromedial and posterolateral fragment. The posteromedial fragment extends into the posterior colliculus of the medial malleolus and has a subchondral impaction fracture. There is also a 1 × 1 cm piece of the articular surface of the posterior malleolus that has flipped 90 degrees and lodged itself between the posterolateral fracture fragment. This video overview and case presentation demonstrates a posteromedial approach with fixation strategy for the posterior malleolus.
High Nonunion and Amputations Rates with either Early Intramedullary Nail Removal versus Retention for Tibial Shaft Fracture Related Infections
Authors: Jones Jenna , Ngo Daniel , Cardon Morgan , Mullis Brian , Weaver Bree , Slaven James E. , McCaskey Meghan , Mir Hassan , Warner Stephen , Achor Timothy , Natoli Roman M.
Published: July 2023

Objectives:

To compare debridement, antibiotics, and implant retention (DAIR) and intramedullary nail (IMN) removal with subsequent strategy for fracture stabilization in the treatment of tibia fracture related infections (FRIs) occurring within 90 days of initial IMN placement.

Design:

Retrospective case-control

Setting:

Four academic, level 1 trauma centers

Patients:

66 patients that subsequently received unplanned operative treatment for FRI diagnosed within 90 days of initial tibia IMN

Intervention:

DAIR versus IMN removal pathways

Main Outcome Measurements:

Fracture union

Results:

Twenty-eight patients (42.4%) were treated with DAIR and 38 (57.6%) via IMN removal with subsequent strategy for fracture stabilization. Mean follow-up was 16.3 months. At final follow-up, ultimate bone healing was achieved in 75.8% (47/62), whereas 24.2% (15/62) had persistent nonunion or amputation. No significant difference was seen in ultimate bone healing (p=.216) comparing DAIR and IMN removal. Factors associated with persistent nonunion or amputation were time from injury to initial IMN (p<.001), McPherson systemic host grade B (p=.046), as well as increasing open fracture grade, with Gustilo-Anderson IIIB/IIIC fractures being the worst (p=.009). Fewer surgeries following initial FRI treatment were positively associated with ultimate bone healing (p=.029).

Conclusions:

Treatment of FRI within 90 days of tibial IMN with either DAIR or IMN removal with subsequent strategy for fracture stabilization results in a high rate, nearly 1 in 4, of persistent nonunion or amputation, with neither appearing superior for improving bone healing outcomes.

Level of Evidence:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Familial Analysis of Nonunion in a Genealogic Population Database Demonstrates No Evidence of Heritable Risk
Authors: Kantor Adam H. , O’Neill Dillon C. , Steffenson Lillia N. , Meeks Huong D. , Fraser Alison M. , Marchand Lucas M. , Haller Justin M.
Published: July 2023

OBJECTIVE:

To determine if there is evidence of heritable risk for nonunion using a large, state-wide population database.

DESIGN:

Database

SETTING:

Level 1 Trauma Center

POPULATION:

All Utah residents from 1996 – 2021 that sustained a long bone fracture and their family members.

OUTCOMES:

The primary outcome was nonunion and the prevalence of nonunion among the patients’ first-, second-, and third-degree relatives. The secondary objective was to identify demographic, injury, and socioeconomic risk factors associated with nonunion.

RESULTS:

In total, 150,263 fractures and 6,577 (4.4%) nonunions were identified. This was highly refined to a 1:3 matched cohort of 4,667 nonunions of 13,981 fractures for familial clustering analysis. Cox proportional hazards did not demonstrate excessive risk of nonunion amongst first- (p = 0.863), second- (p = 0.509), and third-degree relatives (p = 0.252). Further analysis of the entire cohort demonstrated male sex (RR = 1.15; p < 0.001), Medicaid enrollment (RR = 2.64; p < 0.001), open fracture (RR = 2.53; p < 0.001), age group 41-60 (RR = 1.43; p < 0.001), a history of obesity (RR = 1.20; p < 0.001) were independent risk factors for nonunion.

CONCLUSIONS:

Our results demonstrate no evidence of heritable risk for nonunion. Independent risk factors for nonunion were male sex, Medicaid enrollment, open fracture, middle age, and a history of obesity. While it is important to identify modifiable and non-modifiable risk factors, these results continue to support that the risk of nonunion is multifactorial, relating to injury characteristics, operative techniques, and patient specific risk factors.

Level of Evidence:

Level III. See Instructions for Authors for a complete description of levels of evidence.
Updating the Evidence: Systematic Literature Review of Risk Factors and Strategies for Prevention, Diagnosis, and Treatment of Surgical Site Infection After Pediatric Scoliosis Surgery
Authors: Gupta Arjun , Badin Daniel , Leland Christopher R. , Vitale Michael G. , Sponseller Paul D.
Published: July 2023

Background:

Surgical site infection (SSI) is a major potential complication following pediatric spinal deformity surgery that is associated with significant morbidity and increased costs. Despite this, SSI rates remain high and variable across institutions, in part due to a lack of up-to-date, comprehensive prevention, and treatment protocols. Furthermore, few attempts have been made to review the optimal diagnostic modalities and treatment strategies for SSI following scoliosis surgery. The aim of this study was to systematically review current literature on risk factors for SSI in pediatric patients undergoing scoliosis surgery, as well as strategies for prevention, diagnosis, and treatment.

Methods:

On January 19, 2022, a systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies reporting risk factors for acute, deep SSI (<90 d) or strategies for prevention, diagnosis, or treatment of SSI following pediatric scoliosis surgery were included. Each included article was assigned a level of evidence rating based on study design and quality. Extracted findings were organized into risk factors, preventive strategies, diagnostic modalities, and treatment options and each piece of evidence was graded based on quality, quantity, and consistency of underlying data.

Results:

A total of 77 studies met the inclusion criteria and were included in this systematic review, of which 2 were categorized as Level I, 3 as Level II, 64 as Level III, and 8 as Level IV. From these studies, a total of 29 pieces of evidence (grade C or higher) regarding SSI risk factors, prevention, diagnosis, or treatment were synthesized.

Conclusions:

We present an updated review of published evidence for defining high-risk patients and preventing, diagnosing, and treating SSI after pediatric scoliosis surgery. The collated evidence presented herein may help limit variability in practice and decrease the incidence of SSI in pediatric spine surgery.

Level of Evidence:

Level III—systematic review.