bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic performance of PET/CT in the detection of liver metastases in well-differentiated NETs
Authors: Grawe Freba , Rosenberger Natalie , Ingenerf Maria , Beyer Leonie , Eschbach Ralf , Todica Andrei , Seidensticker Ricarda , Schmid-Tannwald Christine , Cyran Clemens C. , Ricke Jens , Bartenstein Peter , Auernhammer Christoph. J. , Ruebenthaler Johannes , Fabritius Matthias P.
Published: April 2023

Background

The aim of this retrospective study was to compare the diagnostic accuracy of somatostatin receptor (SSR)-PET/CT to liver MRI as reference standard in the evaluation of hepatic involvement in neuroendocrine tumors (NET).

Methods

An institutional database was screened for “SSR” imaging studies between 2006 and 2021. 1000 NET Patients (grade 1/2) with 2383 SSR-PET/CT studies and matching liver MRI in an interval of +3 months were identified. Medical reports of SSR-PET/CT and MRI were retrospectively evaluated regarding hepatic involvement and either confirmed by both or observed in MRI but not in SSR-PET/CT (false-negative) or in SSR-PET but not in MRI (false-positive).

Results

Metastatic hepatic involvement was reported in 1650 (69.2%) of the total 2383 SSR-PET/CT imaging studies, whereas MRI detected hepatic involvement in 1685 (70.7%) cases. There were 51 (2.1%) false-negative and 16 (0.7%) false-positive cases. In case of discrepant reports, MRI and PET/CT were reviewed side by side for consensus reading. SSR-PET/CT demonstrated a sensitivity of 97.0% (95%CI: 96.0%, 97.7%), a specificity of 97.7% (95%CI: 96.3%, 98.7%), a PPV of 99.0% (95%CI: 98.4%, 99.4%) and NPV of 93.0% (95%CI: 91.0, 94.8%) in identifying hepatic involvement. The most frequent reason for false-negative results was the small size of lesions with the majority < 0.6 cm.

Conclusion

This study confirms the high diagnostic accuracy of SSR-PET/CT in the detection of hepatic involvement in NET patients based on a patient-based analysis of metastatic hepatic involvement with a high sensitivity and specificity using liver MRI imaging as reference standard. However, one should be aware of possible pitfalls when a single imaging method is used in evaluating neuroendocrine liver metastases in patients.
Artificial intelligence in higher education: the state of the field
Authors: Crompton Helen , Burke Diane
Published: April 2023

This systematic review provides unique findings with an up-to-date examination of artificial intelligence (AI) in higher education (HE) from 2016 to 2022. Using PRISMA principles and protocol, 138 articles were identified for a full examination. Using a priori, and grounded coding, the data from the 138 articles were extracted, analyzed, and coded. The findings of this study show that in 2021 and 2022, publications rose nearly two to three times the number of previous years. With this rapid rise in the number of AIEd HE publications, new trends have emerged. The findings show that research was conducted in six of the seven continents of the world. The trend has shifted from the US to China leading in the number of publications. Another new trend is in the researcher affiliation as prior studies showed a lack of researchers from departments of education. This has now changed to be the most dominant department. Undergraduate students were the most studied students at 72%. Similar to the findings of other studies, language learning was the most common subject domain. This included writing, reading, and vocabulary acquisition. In examination of who the AIEd was intended for 72% of the studies focused on students, 17% instructors, and 11% managers. In answering the overarching question of how AIEd was used in HE, grounded coding was used. Five usage codes emerged from the data: (1) Assessment/Evaluation, (2) Predicting, (3) AI Assistant, (4) Intelligent Tutoring System (ITS), and (5) Managing Student Learning. This systematic review revealed gaps in the literature to be used as a springboard for future researchers, including new tools, such as Chat GPT.
EEG spectral and connectivity parameters as cognitive biomarkers in Parkinson disease
Authors: Elkholy Mostafa M. , Aboubakr Hossam H. , Abd ElMonem Noha A. , Soliman Rasha H. , Masoud Mohammed M.
Published: April 2023

Background

Cognitive decline is a common presentation of Parkinson’s disease (PD) and a continued search exists for a reliable biomarker for early identification and management of this clinical problem. The objective of this study is to select the most useful biomarker in assessment of PD-related cognitive decline. This cross-sectional study included 47 patients with PD and 47 matched healthy controls. All participants were assessed by quantitative electroencephalography (QEEG) spectral (relative power and background peak frequency) and connectivity measures (coherence and phase lag degree), in addition to clinical evaluation using Unified Parkinson’s Disease Rating Scale (UPDRS)and Modified Hoehn and Yahr staging scale and neuropsychological assessment of the patients using Montreal Cognitive Assessment (MoCA).

Results

PD patients showed significantly higher relative power in all frequency bands over the right temporal region with no significant changes in peak frequency, coherence and phase lag degree compared to healthy controls. PD patients with impaired cognition (MoCA < 26) had significantly lower global relative power, more marked in alpha and beta frequency bands compared to PD patients with normal cognition. Alpha and beta relative power in frontal and temporal regions showed significant correlation with different cognitive domains of MoCA score.

Conclusions

QEEG measures especially spectral relative power could be used as adjunct to neuropsychological assessment in evaluation of PD-related cognitive decline.
Effect of levetiracetam and valproate on late-onset post-traumatic seizures
Authors: Wang Yanli , Wang Yiqi , Wang Huifang , Du Xiaoping , Miao Jie , Tao James X. , Sun Meizhen
Published: April 2023

Background

To compare the preventive effects of levetiracetam and valproate on late-onset post-traumatic seizures in patients with traumatic brain injury (TBI).

Methods

A total of 95 patients with TBI were recruited from 2017 to 2020. They were randomized into three groups: levetiracetam (LEV) group (n = 30) receiving LEV treatment (500 mg, bid, po); valproate group (n = 32) receiving sodium valproate (500 mg/d, once daily, po); and control group (n = 33) receiving no anti-seizure medication. LEV and valproate were given to corresponding groups within seven days after TBI, and the administration lasted for one month. The incidence of epilepsy and adverse events were evaluated at 7 days and 12 months post-TBI.

Results

The cumulative incidences of late post-traumatic seizures at the 12-month follow-up in the LEV, valproate, and control groups were 3.33%, 12.50% and 15.63%, respectively. The cumulative incidence of late post-traumatic seizures in the LEV group was significantly lower than those in the valproate and control groups (P < 0.05). The cumulative incidence of late post-traumatic seizure in the valproate group was not significantly different from that in the control group (P > 0.05).

Conclusions

LEV can reduce the cumulative incidence of late post-traumatic seizures, whereas valproate can not.
Ultra-high birefringence with tuneable double zero chromatic dispersion-PCF: a theoretical analysis
Authors: Akowuah Emmanuel Kofi , Agbemabiese Patrick Atsu , Amoah Alexander Kwasi
Published: April 2023

This work presents photonic crystal fibres made up of four hexagonal shape of four rings. Four structures have been designed and configured. The structures show improvement in optical properties consecutively to achieve the optimum configuration. The full vectorial finite-element method is adopted for this work. COMSOL Multiphysics is used for the simulation. The results show a birefringence of 1.308 × 10−2 at 1.55 µm and tuneable double zero dispersion at wavelengths of 0.99 µm and 1.8 µm for x-polarisation mode. Also, the chromatic dispersion of − 24.062 ps/km nm and nonlinear coefficient of 30.32 W−1 km−1 are obtained at a telecommunication wavelength of 1.55 µm. The proposed photonic crystal fibre can be beneficial in nonlinear and supercontinuum applications since photonic crystal fibres of double zero dispersion demonstrate higher power spectral densities than single zero dispersion.
Seismic physical modeling study for a shale oil reservoir with complex lithofacies and meter-scale structures
Authors: Ding Pinbo , Zhang Feng , Chai Yibo , Luo Pingping , Gao Liangliang
Published: April 2023

Shale oil reservoirs usually have various lithofacies with complex spatial patterns. Seismic reflections usually reveal the combination of sets of thin mud shales with various lithofacies. The seismic response characteristics of the lithofacies and the differences in seismic response of different lithofacies are still unclear, making the reservoir description difficult. The complex tectonic structures, diverse lithofacies, thin interlayers, fractures with various length scales, and various fracture development zones in the shale oil reservoir have placed very high demands on the design and construction method during the physical modeling of the shale oil reservoir. Facing these challenges, a physical modeling study on shale oil reservoirs with complex lithofacies and meter-scale structures is conducted. The target is the shale oil reservoir of the [Formula: see text] subsegment in the Jiyang depression. The complex physical model of a shale oil reservoir, with the thin stratigraphic layers and the complicated lithofacies and fracture patterns to date, has been designed and constructed in a laboratory. In total, 25 combinations of materials have been developed to simulate various lithofacies with different elastic parameters, and the error of the wave velocity simulation is less than 2.35%. The simulation of 1 m thick interlayers and the construction method for seismic physical models with meter-scale geologic structures has been realized. The quality control analysis finds that the simulation accuracy of small-scale geologic structure, complex lithofacies, and fractures is relatively reliable. Based on the physical model of the shale oil reservoir, high-density and wide-azimuth seismic data are acquired. Preliminary data processing and analysis find that the model layers have clear reflection characteristics, providing reliable data for the next step of seismic characteristics analysis of complex lithofacies shale oil reservoirs. The methodology has improved the capacity of seismic physical modeling to simulate complex oil and gas reservoirs, enabling the seismic physical simulation method to be applied in analyzing the commonly observed complex lithofacies, fractures, and meter-scale structures in unconventional oil and gas reservoirs.
Expanding the Reach and Grasp of Lung Cancer Screening
Authors: Osarogiagbon Raymond U. , Yang Pan-Chyr , Sequist Lecia V.
Published: April 2023

Low-dose computer tomographic (LDCT) lung cancer screening reduces lung cancer–specific and all-cause mortality among high-risk individuals, but implementation has been challenging. Despite health insurance coverage for lung cancer screening in the United States since 2015, fewer than 10% of eligible persons have participated; striking geographic, racial, and socioeconomic disparities were already evident, especially in the populations at greatest risk of lung cancer and, therefore, most likely to benefit from screening; and adherence to subsequent testing is significantly lower than that reported in clinical trials, potentially reducing the realized benefit. Lung cancer screening is a covered health care benefit in very few countries. Obtaining the full population-level benefit of lung cancer screening will require improved participation of already eligible persons (the grasp of screening) and improved eligibility criteria that more closely match up with the full spectrum of persons at risk (the reach of screening), irrespective of smoking history. We used the socioecological framework of health care to systematically review implementation barriers to lung cancer screening and discuss multilevel solutions. We also discussed guideline-concordant management of incidentally detected lung nodules as a complementary approach to early lung cancer detection that can extend the reach and strengthen the grasp of screening. Furthermore, we discussed ongoing efforts in Asia to explore the possibility of LDCT screening in populations in whom lung cancer risk is relatively independent of smoking. Finally, we summarized innovative technological solutions, including biomarker selection and artificial intelligence strategies, to improve the safety, effectiveness, and cost-effectiveness of lung cancer screening in diverse populations.
Survival of Patients With Neuroblastoma After Assignment to Reduced Therapy Because of the 12- to 18-Month Change in Age Cutoff in Children's Oncology Group Risk Stratification
Authors: Bender Hannah G. , Irwin Meredith S. , Hogarty Michael D. , Castleberry Robert , Maris John M. , Kao Pei-Chi , Zhang Fan F. , Naranjo Arlene , Cohn Susan L. , London Wendy B.
Published: April 2023

PURPOSE

In 2006, Children's Oncology Group (COG) reclassified subgroups of toddlers diagnosed with neuroblastoma from high-risk to intermediate-risk, when the age cutoff for high-risk assignment was raised from 365 days (12 months) to 547 days (18 months). The primary aim of this retrospective study was to determine if excellent outcome was maintained after assigned reduction of therapy.

PATIENTS AND METHODS

Children <3 years old at diagnosis, enrolled on a COG biology study from 1990 to 2018, were eligible (n = 9,189). Assigned therapy was reduced for two cohorts of interest on the basis of the age cutoff change: 365-546 days old with International Neuroblastoma Staging System (INSS) stage 4, MYCN not amplified ( MYCN-NA), favorable International Neuroblastoma Pathology Classification (INPC), hyperdiploid tumors (12-18mo/Stage4/FavBiology), and 365-546 days old with INSS stage 3, MYCN-NA, and unfavorable INPC tumors (12-18mo/Stage3/ MYCN-NA/Unfav). Log-rank tests compared event-free survival (EFS) and overall survival (OS) curves.

RESULTS

For 12-18mo/Stage4/FavBiology, 5-year EFS/OS (± SE) before (≤2006; n = 40) versus after (>2006; n = 55) assigned reduction in therapy was similar: 89% ± 5.1%/89% ± 5.1% versus 87% ± 4.6%/94% ± 3.2% ( P = .7; P = .4, respectively). For 12-18mo/Stage3/ MYCN-NA/Unfav, the 5-year EFS and OS were both 100%, before (n = 6) and after (n = 4) 2006. The 12-18mo/Stage4/FavBiology plus 12-18mo/Stage3/ MYCN-NA/Unfav classified as high-risk ≤2006 had an EFS/OS of 91% ± 4.4%/91% ± 4.5% versus 38% ± 1.3%/43% ± 1.3% for all other high-risk patients <3 years old ( P < .0001; P < .0001, respectively). The 12-18mo/Stage4/FavBiology plus 12-18mo/Stage3/ MYCN-NA/Unfav classified as intermediate-risk >2006 had an EFS/OS of 88% ± 4.3%/95% ± 2.9% versus 88% ± 0.9%/95% ± 0.6% for all other intermediate-risk patients <3 years old ( P = .87; P = .85, respectively).

CONCLUSION

Excellent outcome was maintained among subsets of toddlers with neuroblastoma assigned to reduced treatment after reclassification of risk group from high to intermediate on the basis of new age cutoffs. Importantly, as documented in prior trials, intermediate-risk therapy is not associated with the degree of acute toxicity and late effects commonly observed with high-risk regimens.
Acting on Actionable Mutations in Metastatic Prostate Cancer
Authors: Marshall Catherine H.
Published: April 2023

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology , to patients seen in their own clinical practice.

Approximately a quarter of men with metastatic castration-resistant prostate cancer have genomic alterations within the homologous recombination repair pathway with poly (ADP-ribose) polymerase (PARP) inhibitors as corresponding treatment options. How to incorporate genomic information and associated therapeutic options into treatment decision making and sequencing of therapies in prostate cancer remains challenging. Men with BRCA2 alterations seem to derive the most benefit from PARP inhibitors, and although early treatment in combination with standard therapies has not yet shown an overall survival benefit, there may be other benefits to incorporating PARP inhibitors early for some men.
False Onsager relations
Authors: Campisi Michele
Published: April 2023

Recent research suggests that when a system has a “false time-reversal violation” the Onsager reciprocity relations hold despite the presence of a magnetic field. The purpose of this work is to clarify that the Onsager relations may well be violated in the presence of a “false time-reversal violation”: that rather guarantees the validity of distinct relations, which we dub “false Onsager relations”. We also point out that for quantum systems “false time-reversal violation” is omnipresent and comment that, per se, this has in general no consequence in regard to the validity of Onsager relations, or the more general non-equilibrium fluctuation relations, in the presence of a magnetic field. Our arguments are illustrated with the Heisenberg model of a magnet in an external magnetic field.
Carbohydrate Intake and Oral Glucose Tolerance Test Results in the Postpartum Period
Authors: Rosenberg Emily A , Seely Ellen W , James Kaitlyn , Soffer Marti D , Nelson Stacey , Nicklas Jacinda M , Powe Camille E
Published: April 2023

Context

The American Diabetes Association (ADA) recommends a 3-day preparatory diet prior to a diagnostic oral glucose tolerance test (OGTT), a test often recommended in postpartum individuals with a history of gestational diabetes (GDM).

Objective

Evaluate the relationship between carbohydrate intake and OGTT glucose in 2 cohorts of postpartum individuals.

Methods

We performed analyses of postpartum individuals from 2 prospective studies with recent GDM (Balance after Baby Intervention, BABI, n = 177) or risk factors for GDM (Study of Pregnancy Regulation of INsulin and Glucose, SPRING, n = 104) .We measured carbohydrate intake using 24-hour dietary recalls (SPRING) or Food Frequency Questionnaire (BABI) and performed 2-hour 75-g OGTTs. The main outcome measure was 120-minute post-OGTT glucose.

Results

There was no relationship between carbohydrate intake and 120-minute post-OGTT glucose level in either study population (SPRING: β = 0.03, [−5.5, 5.5] mg/dL, P = .99; BABI: β = −3.1, [−9.5, 3.4] mg/dL, P = .35). Adding breastfeeding status to the model did not change results (SPRING β = −0.14, [−5.7, 5.5] mg/dL, P = .95; BABI β = −3.9, [−10.4, 2.7] mg/dL, P = .25). There was, however, an inverse relationship between glycemic index and 120-minute post OGTT glucose (BABI: β = −1.1, [−2.2, −0.03] mg/dL, P = .04).

Conclusion

Carbohydrate intake is not associated with post-OGTT glucose levels among postpartum individuals. Dietary preparation prior to the OGTT may not be necessary in this population.
Neonatal and Early Infancy Features of Patients With Inactivating PTH/PTHrP Signaling Disorders/Pseudohypoparathyroidism
Authors: Del Sindaco Giulia , Berkenou Jugurtha , Pagnano Angela , Rothenbuhler Anya , Arosio Maura , Mantovani Giovanna , Linglart Agnès
Published: April 2023

Background

Pseudohypoparathyroidism (PHP) and related disorders newly referred to as inactivating PTH/PTHrP signaling disorders (iPPSD) are rare endocrine diseases. Many clinical features including obesity, neurocognitive impairment, brachydactyly, short stature, parathyroid hormone (PTH) resistance, and resistance to other hormones such as thyroid-stimulating hormone (TSH) have been well described, yet they refer mainly to the full development of the disease during late childhood and adulthood.

Objective

A significant delay in diagnosis has been reported; therefore, our objective is to increase awareness on neonatal and early infancy presentation of the diseases. To do so, we analyzed a large cohort of iPPSD/PHP patients.

Methods

We included 136 patients diagnosed with iPPSD/PHP. We retrospectively collected data on birth and investigated the rate of neonatal complications occurring in each iPPSD/PHP category within the first month of life.

Results

Overall 36% of patients presented at least one neonatal complication, far more than the general population; when considering only the patients with iPPSD2/PHP1A, it reached 47% of the patients. Neonatal hypoglycemia and transient respiratory distress appeared significantly frequent in this latter group, ie, 10.5% and 18.4%, respectively. The presence of neonatal features was associated with earlier resistance to TSH (P < 0.001) and with the development of neurocognitive impairment (P = 0.02) or constipation (P = 0.04) later in life.

Conclusion

Our findings suggest that iPPSD/PHP and especially iPPSD2/PHP1A newborns require specific care at birth because of an increased risk of neonatal complications. These complications may predict a more severe course of the disease; however, they are unspecific which likely explains the diagnostic delay.
An Increase in Plasma Sodium Levels Is Associated With an Increase in Osteoblast Function in Chronic SIAD
Authors: Monnerat Sophie , Refardt Julie , Potasso Laura , Meier Christian , Christ-Crain Mirjam
Published: April 2023

Context

Hyponatremia is associated with increased risk for osteoporosis. Preclinical studies in untreated hyponatremia suggest osteoclast upregulation, whereas a clinical study showed improved osteoblast function after hyponatremia normalization in hospitalized patients with syndrome of inappropriate antidiuresis (SIAD).

Objective

This work aimed to investigate the effect of an increase in sodium on bone turnover, that is, the ratio of the osteoblast marker procollagen type 1 N-terminal propeptide (P1NP) to the osteoclast marker cross-linked C-terminal telopeptide of type 1 collagen (CTX), in outpatients with chronic SIAD.

Methods

A predefined secondary analysis was conducted of the 2-month double-blind, crossover, placebo-controlled SANDx Trial (NCT03202667) performed from December 2017 to August 2021. Participants included 11 outpatients with chronic SIAD: 6 women, median age 73 years, who received a 4-week treatment with 25-mg empagliflozin or placebo. Main outcome measures included the relationship between the change in bone formation index (BFI), defined as P1NP/CTX, and the change in plasma sodium levels.

Results

Changes in sodium were positively correlated with changes in BFI and P1NP (BFI: ρ=.55; P < .001; P1NP: ρ=.45; P = .004) but not with CTX (P = .184) and osteocalcin (P = .149). A sodium increase of 1 mmol/l was associated with an increase of 5.21 in BFI (95% CI, 1.41-9.00; P = .013) and with an increase of 1.48 µg/l in P1NP (95% CI, .26-2.62; P = .03). The effect of sodium change on bone markers was independent of the study medication empagliflozin.

Conclusion

An increase in plasma sodium levels in outpatients with chronic hyponatremia due to SIAD, even when mild, was associated with an increase in bone formation index (P1NP/CTX) triggered by an increase in P1NP, a surrogate marker of osteoblast function.
GIPC3 couples to MYO6 and PDZ domain proteins, and shapes the hair cell apical region
Authors: Chatterjee Paroma , Morgan Clive P. , Krey Jocelyn F. , Benson Connor , Goldsmith Jennifer , Bateschell Michael , Ricci Anthony J. , Barr-Gillespie Peter G.
Published: April 2023

GIPC3 has been implicated in auditory function. Here, we establish that GIPC3 is initially localized to the cytoplasm of inner and outer hair cells of the cochlea and then is increasingly concentrated in cuticular plates and at cell junctions during postnatal development. Early postnatal Gipc3KO/KO mice had mostly normal mechanotransduction currents, but had no auditory brainstem response at 1 month of age. Cuticular plates of Gipc3KO/KO hair cells did not flatten during development as did those of controls; moreover, hair bundles were squeezed along the cochlear axis in mutant hair cells. Junctions between inner hair cells and adjacent inner phalangeal cells were also severely disrupted in Gipc3KO/KO cochleas. GIPC3 bound directly to MYO6, and the loss of MYO6 led to altered distribution of GIPC3. Immunoaffinity purification of GIPC3 from chicken inner ear extracts identified co-precipitating proteins associated with adherens junctions, intermediate filament networks and the cuticular plate. Several of immunoprecipitated proteins contained GIPC family consensus PDZ-binding motifs (PBMs), including MYO18A, which bound directly to the PDZ domain of GIPC3. We propose that GIPC3 and MYO6 couple to PBMs of cytoskeletal and cell junction proteins to shape the cuticular plate.
Changes in Immature Reticulocytes Aid the Indirect Detection of Microdose Recombinant Erythropoietin Use in Men and Women
Authors: BREENFELDT ANDERSEN ANDREAS , BEJDER JACOB , BONNE THOMAS CHRISTIAN , GRAAE JONATHAN , SEIER SØREN , NORDSBORG NIKOLAI BAASTRUP
Published: April 2023

Purpose

We investigated whether immature reticulocyte fraction (IRF) and the immature reticulocytes to red blood cells ratio (IR/RBC) are sensitive and specific biomarkers for microdose recombinant human erythropoietin (rHuEPO) and whether the inclusion of reticulocyte percentage (RET%) and the algorithm “abnormal blood profile score (ABPS)” increased the athlete biological passport (ABP) sensitivity compared with hemoglobin concentration ([Hb]) and the OFF-hr score ([Hb]–60 × √RET%).

Methods

Forty-eight (♀ = 24, ♂ = 24) participants completed a 2-wk baseline period followed by a 4-wk intervention period with three weekly intravenous injections of 9 IU·kg−1·bw−1 epoetin β (♀ = 12, ♂ = 12) or saline (0.9% NaCl, ♀ = 12, ♂ = 12) and a 10-d follow-up. Blood samples were collected weekly during baseline and intervention as well as 3, 5, and 10 d after treatment.

Results

The rHuEPO treatment increased [Hb] (time–treatment, P < 0.001), RET% (time–treatment, P < 0.001), IRF (time–treatment, P < 0.001) and IR/RBC (time–treatment, P < 0.001). IRF and IR/RBC were up to ~58% (P < 0.001) and ~141% (P < 0.001) higher compared with placebo, and calculated thresholds provided a peak sensitivity across timepoints of 58% and 54% with ~98% specificity, respectively. To achieve >99% specificity for IRF and IR/RBC, sensitivity was reduced to 46% and 50%, respectively. Across all timepoints, the addition of RET% and ABPS to the ABP increased sensitivity from 29% to 46%. Identification of true-positive outliers obtained via the ABP and IRF and IR/RBC increased sensitivity across all timepoints to 79%.

Conclusions

In summary, IRF, IR/RBC, RET% and ABPS are sensitive and specific biomarkers for microdose rHuEPO in both men and women and complement the ABP.
The lung cancers: staging and response, CT, 18F-FDG PET/CT, MRI, DWI: review and new perspectives
Authors: Owens Cara , Hindocha Sumeet , Lee Richard , Millard Thomas , Sharma Bhupinder
Published: April 2023

Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer deaths in both sexes combined. Recent years have seen major advances in the diagnostic and treatment options for patients with non-small-cell lung cancer (NSCLC), including the routine use of 2-deoxy-2[18F]-fluoro-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) in staging and response evaluation, minimally invasive endoscopic biopsy, targeted radiotherapy, minimally invasive surgery, and molecular and immunotherapies.

In this review, the central roles of CT and 18F-FDG PET/CT in staging and response in both NSCLC and malignant pleural mesothelioma (MPM) are critically assessed. The Tumour Node Metastases (TNM-8) staging systems for NSCLC and MPM are presented with critical appraisal of the strengths and pitfalls of imaging. Overviews of the Response Evaluation Criteria in Solid Tumours (RECIST 1.1) for NSCLC and the modified RECIST criteria for MPM are provided, together with discussion of the benefits and limitations of these anatomical-based tools. Metabolic response assessment (not evaluated by RECIST 1.1) will be explored. We introduce the Positron Emission Tomography Response Criteria in Solid Tumours (PERCIST 1.0) to include its advantages and challenges. The limitations of both anatomical and metabolic assessment criteria when applied to NSCLC treated with immunotherapy and the important concept of pseudoprogression are addressed with reference to immune RECIST (iRECIST).

Separate consideration is given to the diagnosis and follow up of solitary pulmonary nodules with reference to the British Thoracic Society guidelines and Fleischner guidelines and use of the Brock (CT-based) and Herder (addition of 18F-FDG PET/CT) models for assessing malignant potential. We discuss how these models inform decisions by the multidisciplinary team, including referral of suspicious nodules for non-surgical management in patients unsuitable for surgery. We briefly outline current lung screening systems being used in the UK, Europe and North America.

Emerging roles for MRI in lung cancer imaging are reviewed. The use of whole-body MRI in diagnosing and staging NSCLC is discussed with reference to the recent multicentre Streamline L trial. The potential use of diffusion-weighted MRI to distinguish tumour from radiotherapy-induced lung toxicity is discussed. We briefly summarise the new PET-CT radiotracers being developed to evaluate specific aspects of cancer biology, other than glucose uptake. Finally, we describe how CT, MRI and 18F-FDG PET/CT are moving from primarily diagnostic tools for lung cancer towards having utility in prognostication and personalised medicine with the agency of artificial intelligence.
The genome sequence of the Diamond-back Marble, Eudemis profundana (Denis & Schiffermüller, 1775)
Authors: Boyes Douglas , Hammond James ,   University of Oxford and Wytham Woods Genome Acquisition Lab,   Darwin Tree of Life Barcoding collective,   Wellcome Sanger Institute Tree of Life programme,   Wellcome Sanger Institute Scientific Operations: DNA Pipelines collective,   Tree of Life Core Informatics collective,   Darwin Tree of Life Consortium
Published: April 2023

We present a genome assembly from an individual male Eudemis profundana (the Diamond-back Marble; Arthropoda; Insecta; Lepidoptera; Tortricidae). The genome sequence is 691.3 megabases in span. Most of the assembly is scaffolded into 28 chromosomal pseudomolecules, including the Z sex chromosome. The mitochondrial genome has also been assembled and is 16.5 kilobases in length.
SMA Therapy in Poland: New Hopes and Challenges
Authors: Welian Iwona , Gendek Karolina , Jastrzębska Ilona , Maliszewska Karolina , Chrościńska-Krawczyk Magdalena
Published: April 2023

Abstract: Spinal muscular atrophy (SMA) is a genetically inherited disease whose symptoms appear in children at a fairly early age. The main cause of the disease is a mutation of the SMN1 gene, which causes the lack of production of SMN This results in the disappearance of motoneurons, which consequently leads to the disappearance of the patient's ability to move and his death. An important element of coping with the disease is its early detection in newborn screening, because the earlier we start the drug, the greater the chance that the patient will maintain motor efficiency. The article describes treatment options for children in Poland, i. e. the use of such drugs as Nusinersen, which increases the amount of SMN protein, gene therapy Onasemnogen aeparvovec, which increases the amount of SMN gene, Ridisplam, which increases the amount of SMN protein, and salbutamol, which helps patients to breathe. The article also provides information about new drug therapies for the treatment of SMA and the stage of clinical trials at which they are currently being developed. It is important to look for new solutions in the treatment of SMA.

Objective: To familiarize the readers of the article with the problems of SMA treatment in Poland, as well as to broaden their knowledge of new available drugs for the treatment of this disease.
Marketplace Leakage
Authors: Hagiu Andrei , Wright Julian
Published: April 2023

A key issue for the design of online marketplaces is addressing leakage. Buyers may use the marketplace to discover a seller or to obtain certain conveniences, but the seller may then want to take transactions off the marketplace to avoid transaction fees. Assuming buyers are heterogenous in their switching cost or inconvenience cost of purchasing directly, we provide a model in which there is partial leakage in equilibrium. We use the model to analyze the trade-offs associated with different strategies the marketplace can use to attenuate the effects of leakage: investing in transaction benefits, limiting communication, charging referral fees, using price-parity clauses, introducing seller competition on the marketplace, and hiding sellers that try to induce too much leakage.

This paper was accepted by Joshua Gans, business strategy.

Supplemental Material: The online appendix is available at https://doi.org/10.1287/mnsc.2023.4757 .
Multimodal Vaccine Distribution Network Design with Drones
Authors: Enayati Shakiba , Li Haitao , Campbell James F. , Pan Deng
Published: April 2023

Childhood vaccines play a vital role in social welfare, but in hard-to-reach regions, poor transportation, and a weak cold chain limit vaccine availability. This opens the door for the use of vaccine delivery by drones (uncrewed aerial vehicles, or UAVs) with their fast transportation and reliance on little or no infrastructure. In this paper, we study the problem of strategic multimodal vaccine distribution, which simultaneously determines the locations of local distribution centers, drone bases, and drone relay stations, while obeying the cold chain time limit and drone range. Two mathematical optimization models with complementary strengths are developed. The first model considers the vaccine travel time at the aggregate level with a compact formulation, but it can be too conservative in meeting the cold chain time limit. The second model is based on the layered network framework to track the vaccine flow and travel time associated with each origin-destination (OD) pair. It allows the number of transshipments and the number of drone stops in a vaccine flow path to be limited, which reflects practical operations and can be computationally advantageous. Both models are applied for vaccine distribution network design with two types of drones in Vanuatu as a case study. Solutions with drones using our parameter settings are shown to generate large savings, with differentiated roles for large and small drones. To generalize the empirical findings and examine the performance of our models, we conduct comprehensive computational experiments to assess the sensitivity of optimal solutions and performance metrics to key problem parameters.

History: This paper has been accepted for the Transportation Science Special Issue on Emerging Topics in Transportation Science and Logistics.

Funding: This work was supported by the Association for Supply Chain Management (ASCM) and the University of Missouri Research Board (UMSL Award 0059109).

Supplemental Material: The online supplement is available at https://doi.org/10.1287/trsc.2023.1205 .
A new algorithm for the management of diabetic foot ulcer: recommendations from Central and Eastern Europe
Authors: Bem Robert , Chadwick Paul , Cvjetko Ivan , Koliba Miroslav , Kokeny Zoltan , Lipinski Przemyslaw , Mrozikiewicz-Rakowska Beata , Rozsos Istvan , Wegrzynowski Adam
Published: April 2023

There is wide regional variation in clinical practice and access to treatment for patients with diabetic foot ulcer (DFU) from countries in Central and Eastern Europe (CEE). A treatment algorithm that reflects current treatment practices while providing a common framework may facilitate best practice in DFU management and improve outcomes across the CEE region. Following a series of regional advisory board meetings with experts from Poland, the Czech Republic, Hungary and Croatia, we present consensus recommendations for the management of DFU and outline the key features of a unified algorithm for dissemination and use as a quick tool in clinical practice in CEE. The algorithm should be accessible to specialists as well as non-specialist clinicians and should incorporate: patient screening; checkpoints for assessment and referral; triggers of treatment change; and strategies for infection control, wound bed preparation and offloading. Among adjunctive treatments in DFU, there is a clear role for topical oxygen therapy, which can be used concomitantly with most existing treatment regimens in hard-to-heal wounds following standard of care. Countries from CEE face a number of challenges in the management of DFU. It is hoped that such an algorithm will help standardise the approach to DFU management and overcome some of these challenges. Ultimately, a regionwide treatment algorithm in CEE has the potential to improve clinical outcomes and save limbs.
Evidence of bacterial biofilms within acute wounds: a systematic review
Authors: Patenall Bethany L , Ridgley Joanne D , Jenkins A Toby A , Young Amber E
Published: April 2023

Objective:

The prevalence and role of biofilm formation in acute wounds has seldom been investigated. Understanding the presence of biofilm in acute wounds would allow earlier, biofilm-targeted management, thus decreasing the morbidity and mortality associated with wound infection, improving patient experience and potentially reducing healthcare costs. The purpose of this study was to summarise the evidence for biofilm formation within acute wounds.

Method:

We conducted a systematic literature review for studies which reported evidence of bacterial biofilm formation in acute wounds. An electronic search of four databases was carried out, without restrictions on date. The search terms included ‘bacteria’, ‘biofilm’, ‘acute’ and ‘wound’.

Results:

A total of 13 studies met the inclusion criteria. Of the studies, 69.2% showed evidence of biofilm formation within 14 days of acute wound formation, with 38.5% showing evidence of biofilm 48 hours after wound formed.

Conclusion:

The evidence from this review suggests that biofilm formation plays a greater role within acute wounds than previously considered.
Effect of supplements/intensive nutrition on pressure ulcer healing: a multicentre, randomised controlled study
Authors: Banks Merrilyn D , Webster Joan , Bauer Judy , Dwyer Kathleen , Pelecanos Anita , MacDermott Paula , Nevin Amy , Coleman Kerrie , Campbell Jill , Hickling Donna , Byrnes Angela , Capra Sandra
Published: April 2023

Objective:

To investigate the effectiveness of an intensive nutrition intervention or use of wound healing supplements compared with standard nutritional care in pressure ulcer (PU) healing in hospitalised patients.

Method:

Adult patients with a Stage II or greater PU and predicted length of stay (LOS) of at least seven days were eligible for inclusion in this pragmatic, multicentre, randomised controlled trial (RCT). Patients with a PU were randomised to receive either: standard nutritional care (n=46); intensive nutritional care delivered by a dietitian (n=42); or standard care plus provision of a wound healing nutritional formula (n=43). Relevant nutritional and PU parameters were collected at baseline and then weekly or until discharge.

Results:

Of the 546 patients screened, 131 were included in the study. Participant mean age was 66.1±16.9 years, 75 (57.2%) were male and 50 (38.5%) were malnourished at recruitment. Median length of stay was 14 (IQR: 7–25) days and 62 (46.7%) had ≥2 PUs at the time of recruitment. Median change from baseline to day 14 in PU area was –0.75cm2 (IQR: –2.9_–0.03) and mean overall change in Pressure Ulcer Scale for Healing (PUSH) score was –2.9 (SD 3.2). Being in the nutrition intervention group was not a predictor of change in PUSH score, when adjusted for PU stage or location on recruitment (p=0.28); it was not a predictor of PU area at day 14, when adjusted for PU stage or area on recruitment (p=0.89) or PU stage and PUSH score on recruitment (p=0.91), nor a predictor of time to heal.

Conclusion:

This study failed to confirm a significant positive impact on PU healing of use of an intensive nutrition intervention or wound healing supplements in hospitalised patients. Further research that focuses on practical mechanisms to meet protein and energy requirements is needed to guide practice.
Wound pH and temperature as predictors of healing: an observational study
Authors: Derwin Rosemarie , Patton Declan , Strapp Helen , Moore Zena
Published: April 2023

Objective:

The aim of this study was to measure wound pH, wound temperature and wound size together to gain further understanding of their impact as predictors of wound healing outcomes.

Method:

This study employed a quantitative non-comparative, prospective, descriptive observational design. Participants with both acute and hard-to-heal (chronic) wounds were observed weekly for four weeks. Wound pH was measured using pH indicator strips, wound temperature was measured using an infrared camera and wound size was measured using the ruler method.

Results:

Most of the 97 participants (65%, n=63) were male; participant's ages ranged between 18 and 77 years (mean: 42±17.10. Most of the wounds observed were surgical 60%, (n=58) and 72% (n=70) of the wounds were classified as acute, with 28% (n=27) classified as hard-to-heal wounds. At baseline, there was no significant difference in pH between acute and hard-to-heal wounds; overall the mean pH was 8.34±0.32, mean temperature was 32.86±1.78°C) and mean wound area was 910.50±1132.30mm2. In week 4, mean pH was 7.71±1.11, mean temperature was 31.90±1.76°C and mean wound area was 339.90±511.70mm2. Over the study follow-up period, wound pH ranged from 5–9, from week 1 to week 4, mean pH reduced by 0.63 units from 8.34 to 7.71. Furthermore, there was a mean 3% reduction in wound temperature and a mean 62% reduction in wound size.

Conclusion:

The study demonstrated that a reduction in pH and temperature was associated with increased wound healing as evidenced by a corresponding reduction in wound size. Thus, measuring pH and temperature in clinical practice may provide clinically meaningful data pertaining to wound status.
The short-term prognosis of diabetic foot ulceration is independent of nutritional status at admission
Authors: Feron Florine , Amouyal Chloé , Hartemann Agnès , Van Georges Ha , Bourron Olivier , Dierick-Gallet Anne , Michaux Caroline , Santos Maude Dos , Baudot Magali , Devaux Gaelle , Taboureau Olivier , Andreelli Fabrizio
Published: April 2023

Diabetic foot ulcers are one of the complications of diabetes. Malnutrition is one of the risk factors for wounds but, on the other hand, diabetic foot ulceration may promote malnutrition. In this single-centre retrospective study we evaluated the frequency of malnutrition at first admission and the severity of foot ulceration. We demonstrated that malnutrition at admission correlated with duration of hospitalisation and with death rate rather than with the risk of amputation. Our data challenged the concept that protein-energy deficiency may worsen the prognosis of diabetic foot ulcers. Nevertheless, it is still important to screen nutritional status at baseline and during the follow-up in order to start specific nutritional support therapy as soon as possible in order to reduce morbidity/mortality related to malnutrition.
Evaluation of functional outcome of calcaneal fractures using Essex-Lopresti technique
Authors: Kharat Atul A , Biraris Sandeep R , Chikhalikar Pramod P , Ali Sheran , Goud G Krishna Naresh
Published: April 2023

Background: Calcaneum fractures account for approximately 2% of all fractures, with displaced intra-articular fractures comprising 60-75% of these injuries of which 10% have associated spine fractures and 26% are associated with other extremity injuries. Several authors have reported that patients may be totally incapacitated for up to 3 years and partially impaired for up to 5 years post injury, Although modern surgical techniques have improved the outcome, controversy still exists regarding classification, treatment, operative technique, and post-operative management. Materials and Methods: 28 out of 31 cases were analyzed prospectively and retrospectively from July 2011 to August 2013 after local ethical and scientific clearance. Three patients had lost to follow-up. All patients with calcaneum fractures above age of 18 with either simple or open injuries were included in the study, excluding pediatric and complex injuries. All patients were clinically evaluated and Bohler’s, Gissane’s angles were calculated preoperatively. All patients were treated with one of the modalities, which include conservative, Steinmann pinning, and Calcaneum plate fixation. All patients were followed up in outpatient basis fortnightly for 3 months and on 6th month and 1 year respectively, to check signs of union of fracture, subtalar movements, and complications if any. After radiological evaluation, functional outcome assessment was done using American Orthopaedic Foot and Ankle Society Results: Mean age was 35.1 with range 20-52 years, male to female ratio of 9:1. 85% were due to high-velocity trauma. The most common type of injury was tongue type. Preoperative mean Bohler’s and Gissane’s angles which were about 14.87 and 121.5 degrees respectively, the improved angles postoperatively were 25.68 and 104.37 degrees. One patient had heel pain, one patient had residual edema, one patient developed subtalar and ankle stiffness, there was one case of tendocalcaneus weakness, one with broadening of heel, and one case of wound infection. Conclusion: Undisplaced or minimally displaced calcaneum fractures are best-treated conservatively with cast immobilization for 6 weeks. Essex-Lopresti technique of reduction was superior technique for displaced fractures and achievement of Bohler’s and Gissane’s angle to the after reduction was judgemental for optimal functional outcome. Keywords: Calcaneum, Essex-Lopresti, functional outcome.
ABCD transfer matrix model of Gaussian beam propagation in plano-concave optical microresonators
Authors: Martin-Sanchez David , Li Jing , Zhang Edward Z. , Beard Paul C. , Guggenheim James A.
Published: April 2023

Plano-concave optical microresonators (PCMRs) are optical microcavities formed of one planar and one concave mirror separated by a spacer. PCMRs illuminated by Gaussian laser beams are used as sensors and filters in fields including quantum electrodynamics, temperature sensing, and photoacoustic imaging. To predict characteristics such as the sensitivity of PCMRs, a model of Gaussian beam propagation through PCMRs based on the ABCD matrix method was developed. To validate the model, interferometer transfer functions (ITFs) calculated for a range of PCMRs and beams were compared to experimental measurements. A good agreement was observed, suggesting the model is valid. It could therefore constitute a useful tool for designing and evaluating PCMR systems in various fields. The computer code implementing the model has been made available online.