bluuebunny/crossref_metadata_2025 huggingface dataset:
Preparedness and training of genetic counselors practicing in inpatient settings
Authors: Mancl Nelliann , Myers Melanie F. , Miller Erin M. , Jackson Farrah , Widmeyer Kimberly
Published: August 2023

As rapid genomic testing technology increasingly allows for real‐time answers that could alter management for acutely ill patients, opportunities for genetic counselors to work in inpatient settings will increase. However, genetic counselors' preparedness and the training provided by graduate programs to work in inpatient settings are unknown. We conducted semi‐structured interviews with 13 genetic counselors who provided services in varied inpatient settings to assess genetic counselors' readiness for inpatient positions. We also surveyed members of the Association of Genetic Counseling Program Directors (AGCPD) about inpatient training practices of genetic counseling graduate programs. Genetic counselors were recruited through the National Society of Genetic Counselors (NSGC) Inpatient Special Interest Group listserv and graduate program faculty were recruited through the AGCPD listserv. Some challenges reported by genetic counselors in inpatient settings included working in a fast‐paced hospital environment which necessitated focused interactions with patients; collaborating with diverse providers who may not understand the role of genetic counselors; and navigating grief experiences of families and of themselves as a provider. Although genetic counselors felt that many of their skills developed in graduate school were transferrable to the inpatient setting, those who had minimal or no inpatient exposure in graduate school often described feeling unprepared for working in the inpatient setting. The majority of AGCPD respondents (23/28) indicated their program provided some type of exposure to the inpatient setting for students, the most common (22/23) being an inpatient clinical rotation, which suggests many graduate programs are already recognizing the importance of providing inpatient training. Our findings indicate that while many skills are transferrable to inpatient positions, genetic counselors face unique challenges in inpatient settings. Our results suggest that graduate exposure to the inpatient setting and professional support of inpatient genetic counselors are beneficial to support genetic counselors' preparedness to take on inpatient positions.
Enzymatic synthesis of halogen derivatives of L‐phenylalanine and phenylpyruvic acid stereoselectively labeled with hydrogen isotopes in the side chain
Authors: Pałka Katarzyna , Podsadni Katarzyna , Pająk Małgorzata
Published: August 2023

Halogenated, labeled with deuterium, tritium or doubly labeled with deuterium and tritium in the 3S position of the side chain isotopomers of L‐phenylalanine and phenylpyruvic acid were synthesized. Isotopomers of halogenated L‐phenylalanine were obtained by addition of ammonia from isotopically enriched buffer solution to the halogenated derivative of (E)‐cinnamic acid catalyzed by phenylalanine ammonia lyase. Isotopomers of halogenated phenylpyruvic acid were obtained enzymatically by conversion of the appropriate isotopomer of halogenated L‐phenylalanine in the presence of phenylalanine dehydrogenase. As a source of deuterium was used deuterated water, as a source of tritium was used a solution of highly diluted tritiated water. The labeling takes place in good yields and with high deuterium atom% abundance.
A new discovery in the permafrost of Yakutia sheds light on the nasal horn morphology of the woolly rhinoceros
Authors: Belyaev Ruslan I. , Boeskorov Gennady G. , Cheprasov Maksim Yu. , Prilepskaya Natalya E.
Published: August 2023

Extinct woolly rhinoceroses were iconic representatives of the Late Pleistocene mammoth fauna of Eurasia. These animals were characterized by two huge keratinous horns. In adults, the length of the nasal horn often exceeded one meter. The nasal horn of Coelodonta was characterized by an unusual feature for rhinoceroses—the width of its base was considerably narrower than the width of the rugosity area on the nasal bones of the skull. In this study, a new discovery of woolly rhinoceros' nasal horn in the permafrost of Yakutia is described. This specimen shows that the shape of the base of the woolly rhino's nasal horn corresponds well to the shape (length and width) of the nasal rugosity area. The base of the nasal horn of Coelodonta was markedly elongated anteroposteriorly compared to extant rhinoceroses. Its length was about 150% of the width. We therefore suggest that the narrower shape of the nasal horn base in the majority of previously found specimens was associated with secondary damage after burial caused by maceration.
An Empirical Approach to Derive Water T1 from Multiparametric MR Images Using an Automated Pipeline and Comparison With Liver Stiffness
Authors: Michelotti Filippo C. , Kupriyanova Yuliya , Mori Tim , Küstner Thomas , Heilmann Geronimo , Bombrich Maria , Möser Clara , Schön Martin , Kuss Oliver , Roden Michael , Schrauwen‐Hinderling Vera B.
Published: August 2023

Background

Water T1 of the liver has been shown to be promising in discriminating the progressive forms of fatty liver diseases, inflammation, and fibrosis, yet proper correction for iron and lipid is required.

Purpose

To examine the feasibility of an empirical approach for iron and lipid correction when measuring imaging‐based T1 and to validate this approach by spectroscopy on in vivo data.

Study Type

Retrospective.

Population

Next to mixed lipid‐iron phantoms, individuals with different hepatic lipid content were investigated, including people with type 1 diabetes (N = 15, %female = 15.6, age = 43.5 ± 14.0), or type 2 diabetes mellitus (N = 21, %female = 28.9, age = 59.8 ± 9.7) and healthy volunteers (N = 9, %female = 11.1, age = 58.0 ± 8.1).

Field Strength/Sequences

3 T, balanced steady‐state free precession MOdified Look‐Locker Inversion recovery (MOLLI), multi‐ and dual‐echo gradient echo Dixon, gradient echo magnetic resonance elastography (MRE).

Assessment

T1 values were measured in phantoms to determine the respective correction factors. The correction was tested in vivo and validated by proton magnetic resonance spectroscopy (1H‐MRS). The quantification of liver T1 based on automatic segmentation was compared to the T1 values based on manual segmentation. The association of T1 with MRE‐derived liver stiffness was evaluated.

Statistical Tests

Bland–Altman plots and intraclass correlation coefficients (ICCs) were used for MOLLI vs. 1H‐MRS agreement and to compare liver T1 values from automatic vs. manual segmentation. Pearson's r correlation coefficients for T1 with hepatic lipids and liver stiffness were determined. A P‐value of 0.05 was considered statistically significant.

Results

MOLLI T1 values after correction were found in better agreement with the 1H‐MRS‐derived water T1 (ICC = 0.60 [0.37; 0.76]) in comparison with the uncorrected T1 values (ICC = 0.18 [−0.09; 0.44]). Automatic quantification yielded similar liver T1 values (ICC = 0.9995 [0.9991; 0.9997]) as with manual segmentation. A significant correlation of T1 with liver stiffness (r = 0.43 [0.11; 0.67]) was found. A marked and significant reduction in the correlation strength of T1 with liver stiffness (r = 0.05 [−0.28; 0.38], P = 0.77) was found after correction for hepatic lipid content.

Data Conclusion

Imaging‐based correction factors enable accurate estimation of water T1 in vivo.

Level of Evidence

1

Technical Efficacy

Stage 1
A Fully Automatic Method to Segment Choroid Plexuses in Multiple Sclerosis Using Conventional MRI Sequences
Authors: Storelli Loredana , Pagani Elisabetta , Rubin Martina , Margoni Monica , Filippi Massimo , Rocca Maria A.
Published: August 2023

Background

Choroid plexus (CP) volume has been recently proposed as a proxy for brain neuroinflammation in multiple sclerosis (MS).

Purpose

To develop and validate a fast automatic method to segment CP using routinely acquired brain T1‐weighted and FLAIR MRI.

Study Type

Retrospective.

Population

Fifty‐five MS patients (33 relapsing–remitting, 22 progressive; mean age = 46.8 ± 10.2 years; 31 women) and 60 healthy controls (HC; mean age = 36.1 ± 12.6 years, 33 women).

Field Strength/Sequence

3D T2‐weighted FLAIR and 3D T1‐weighted gradient echo sequences at 3.0 T.

Assessment

Brain tissues were segmented on T1‐weighted sequences and a Gaussian Mixture Model (GMM) was fitted to FLAIR image intensities obtained from the ventricle masks of the SIENAX. A second GMM was then applied on the thresholded and filtered ventricle mask. CP volumes were automatically determined and compared with those from manual segmentation by two raters (with 3 and 10 years' experience; reference standard). CP volumes from previously published automatic segmentation methods (freely available Freesurfer [FS] and FS‐GMM) were also compared with reference standard. Expanded Disability Status Scale (EDSS) score was assessed within 3 days of MRI. Computational time was assessed for each automatic technique and manual segmentation.

Statistical Tests

Comparisons of CP volumes with reference standard were evaluated with Bland Altman analysis. Dice similarity coefficients (DSC) were computed to assess automatic CP segmentations. Volume differences between MS and HC for each method were assessed with t‐tests and correlations of CP volumes with EDSS were assessed with Pearson's correlation coefficients (R). A P value <0.05 was considered statistically significant.

Results

Compared to manual segmentation, the proposed method had the highest segmentation accuracy (mean DSC = 0.65 ± 0.06) compared to FS (mean DSC = 0.37 ± 0.08) and FS‐GMM (0.58 ± 0.06). The percentage CP volume differences relative to manual segmentation were −0.1% ± 0.23, 4.6% ± 2.5, and −0.48% ± 2 for the proposed method, FS, and FS‐GMM, respectively. The Pearson's correlations between automatically obtained CP volumes and the manually obtained volumes were 0.70, 0.54, and 0.56 for the proposed method, FS, and FS‐GMM, respectively. A significant correlation between CP volume and EDSS was found for the proposed automatic pipeline (R = 0.2), for FS‐GMM (R = 0.3) and for manual segmentation (R = 0.4). Computational time for the proposed method (32 ± 2 minutes) was similar to the manual segmentation (20 ± 5 minutes) but <25% of the FS (120 ± 15 minutes) and FS‐GMM (125 ± 15 minutes) methods.

Data Conclusion

This study developed an accurate and easily implementable method for automatic CP segmentation in MS using T1‐weighted and FLAIR MRI.

Evidence Level

1

Technical Efficacy

Stage 4
The prognostic significance of surgical resection margins for local recurrence, distant metastasis, and overall survival in sarcoma
Authors: Stauss Ricarda , Aigner Alexander , Richter Alena , Suero Eduardo , Altemeier Anna , Savov Peter , Ettinger Max , Omar Mohamed
Published: August 2023

Background and Objectives

Surgical resection with microscopically negative margins constitutes one of the key elements of a curative therapeutic approach for localized sarcomas. However, the prognostic value of quantitative margin width remains controversial. We sought to determine the prognostic significance of margin status and margin width for local recurrence (LR), distant recurrence (DR), and overall survival.

Methods

Retrospective analysis of 210 patients undergoing resection of localized sarcoma between 1997 and 2018 at a national sarcoma reference center.

Results

Logistic regression did not reveal an effect of metric margin width as a prognostic factor for LR (odds ratio [OR] = 0.98, p = 0.574), DR (OR = 1, p = 0.908), or overall survival (hazard ratio = 0.98, 95% confidence interval = 0.73–1.20, p = 0.609). Subgroup analysis revealed no differences between complete first resections (R0) and re‐resections (re‐R0) following unplanned R1‐resections for LR (p = 0.727) and overall survival (p = 0.125), but a significantly higher DR‐rate in re‐R0 cases (p = 0.022).

Conclusions

Achieving a negative margin is essential in sarcoma surgery, however, metric margin width was not associated with disease‐specific outcomes. Re‐resection of unplanned R1‐resections should be performed to control for LR and overall survival rates. As re‐R0 cases were at significantly higher risk of DR, these patients should be followed up closely in standardized surveillance protocols.
Accuracy of DOTATATE PET imaging in the preoperative planning of small bowel neuroendocrine tumor resection
Authors: Zhang Chi , Gudmundsdottir Hallbera , Takahashi Hiroaki , Day Courtney , Glasgow Amy , Wasif Nabil , Starlinger Patrick , Warner Susanne , Grotz Travis , Smoot Rory , Truty Mark , Cleary Sean , Kendrick Michael , Nagorney David , Navin Patrick , Halfdanarson Thorvardur R. , Thiels Cornelius
Published: August 2023

Background and Objectives

We assessed the accuracy of preoperative gallium‐68 DOTA‐Tyr3‐octreotate (DOTATATE) positron emission tomography (PET) imaging in estimating multifocality and nodal metastases of small bowel neuroendocrine tumors (sbNETs).

Methods

A multicenter analysis was performed on patients with sbNETs who underwent preoperative DOTATATE PET imaging and surgical resection, with manual palpation of the entire length of the small bowel, between January 2016 and August 2022. Preoperative imaging reports and blinded secondary imaging reviews were compared to the final postoperative pathology reports. Descriptive statistics were applied.

Results

One‐hundred and four patients met inclusion criteria. Pathology showed 53 (51%) patients had multifocal sbNETs and 96 (92%) had nodal metastases. The original preoperative DOTATATE PET imaging identified multifocal sbNET in 28 (27%) patients and lymph node (LN) metastases in 80 (77%) patients. Based on original radiology reports, sensitivity for multifocal sbNET identification was 45%, specificity was 92%, positive predictive value (PPV) was 86%, and negative predictive value (NPV) was 62%. For the identification of LN metastases, sensitivity was 82%, specificity was 88%, PPV was 99%, and NPV was 29%.

Conclusions

Although DOTATATE PET imaging is specific and relatively accurate, sensitivity and NPV are insufficient to guide surgical planning. Preoperative use should not replace open palpation to identify additional synchronous lesions or to omit regional lymphadenectomy.
Long‐term surveillance of branch‐duct intraductal papillary mucinous neoplasms without worrisome or high‐risk features
Authors: Lattimore Courtney M. , Kane William J. , Subbarao Shalini , Venitti Corinne , Cramer Christopher L. , Turkheimer Lena M. , Bauer Todd W. , Turrentine Florence E. , Zaydfudim Victor M.
Published: August 2023

Introduction

Long‐term data evaluating clinical outcomes in patients with branch‐duct Intraductal papillary mucinous neoplasms (BD‐IPMN) without high‐risk stigmata (HRS) or worrisome features (WF) remain limited.

Methods

This observational cohort study included all patients diagnosed with BD‐IPMN without HRS or WF between 2003 and 2019 who were enrolled in a prospective surveillance program. Time‐to‐progression analysis was performed using a cumulative incidence function plot and survival analysis was conducted using Kaplan–Meier.

Results

The median follow‐up time for the 267 patient cohort was 44.5 months (interquartile range [IQR]: 24.1–72.2). Radiographic cyst growth was observed in 123 (46.1%) patients; 65 (24.3%) patients progressed to WF/HRS. Twenty‐six (9.7%) patients were selected for resection during surveillance: 21 (80.8%) WF, 4 (15.4%) HRS; 1 (3.9%) transformed to mixed‐duct. Of all the patients who underwent resection, 5 (19.2%) had adenocarcinoma, and 1 (3.8%) had carcinoma‐in‐situ. The probability of any radiographic progression was 21.3% (5‐year) and 51.3% (10‐year). For the entire cohort, there was 1.1% mortality secondary to pancreatic adenocarcinoma and 8.2% all‐cause mortality. The 5‐year overall survival rate was 91.5%, and at 10 years, 81.5%.

Conclusion

Approximately one in four patients with nonworrisome BD‐IPMN have progression to WF/HRS stigmata during surveillance. However, the risk of malignant transformation remains low. Surveillance strategy remains prudent in this patient population.
Sponge‐nested polymer monoliths: Versatile materials for the solid‐phase extraction of bisphenols
Authors: Morales Natalia , Thickett Stuart C. , Maya Fernando
Published: August 2023

Polymer monoliths are promising materials for sample preparation due to their high porosity, pH stability, and simple preparation. The use of melamine formaldehyde foams has been reported as an effective support to prepare highly robust silica and polymer monoliths. Herein, divinylbenzene monoliths based on a 50:50 (%, w/w) crosslinker/porogen ratio have been nested within a melamine‐formaldehyde sponge, resulting in monoliths with a surface area higher than 400 m2/g. The extraction performance of these monoliths was evaluated for the extraction of endocrine‐disrupting bisphenols from aqueous solutions. We evaluated for the first time the versatility of sponge‐nested polymer monoliths by comparing three different extraction modes (vortex mixing, magnetic stirring, and orbital shaking). Vortex mixing showed a comparable recovery of bisphenols (39%–81%) in a shorter extraction time (30 min, instead of 2 h). In addition, the robustness of the sponge‐nested polymer monoliths was demonstrated for the first time by reshaping a larger monolithic cube (0.125 cm3) into four smaller pieces (4 × 0.03125 cm3) leading to a 16%–21% increase in extraction efficiency. This effect was attributed to an increase in the effective contact area with the sample, obtaining a higher analyte extraction capacity.
Ultralow flow liquid chromatography and related approaches: A focus on recent bioanalytical applications
Authors: Greguš Michal , Ivanov Alexander R. , Wilson Steven Ray
Published: August 2023

Ultralow flow LC employs ultra‐narrow bore columns and mid‐range pL/min to low nL/min flow rates (i.e., ≤20 nL/min). The separation columns that are used under these conditions are typically 2–30 μm in inner diameter. Ultralow flow LC systems allow for exceptionally high sensitivity and frequently high resolution. There has been an increasing interest in the analysis of scarce biological samples, for example, circulating tumor cells, extracellular vesicles, organelles, and single cells, and ultralow flow LC was efficiently applied to such samples. Hence, advances towards dedicated ultralow flow LC instrumentation, technical approaches, and higher throughput (e.g., tens‐to‐hundreds of single cells analyzed per day) were recently made. Here, we review the types of ultralow flow LC technology, followed by a discussion of selected representative ultralow flow LC applications, focusing on the progress made in bioanalysis of amount‐limited samples during the last 10 years. We also discuss several recently reported high‐sensitivity applications utilizing flow rates up to 100 nL/min, which are below commonly used nanoLC flow rates. Finally, we discuss the path forward for future developments of ultralow flow LC.
Engineering Biomimetic Microenvironment for Organoid
Authors: Chen Shuo , Wang Lijuan , Yang Lei , Rana Abdus Samad , He Chuanglong
Published: August 2023

Organoid is an emerging frontier technology in the field of life science, in which pluripotent stem cells or tissue‐derived differentiated/progenitor cells form 3D structures according to their multi‐directional differentiation potential and self‐assembly ability. Nowadays, although various types of organoids are widely investigated, their construction is still complicated in operation, uncertain in yield, and poor in reproducibility for the structure and function of native organs. Constructing a biomimetic microenvironment for stem cell proliferation and differentiation in vitro is recognized as a key to driving this field. This review reviews the recent development of engineered biomimetic microenvironments for organoids. First, the composition of the matrix for organoid culture is summarized. Then, strategies for engineering the microenvironment from biophysical, biochemical, and cellular perspectives are discussed in detail. Subsequently, the newly developed monitoring technologies are also reviewed. Finally, a brief conclusion and outlook are presented for the inspiration of future research.
Mechanical Strain Tailoring via Magnetic Field Assisted 3D Printing of Iron Particles Embedded Polymer Nanocomposites
Authors: Afshari Pantea , Pavlyuk Maryna , Lira Cristian , Katnam Kali‐Babu , Bodaghi Mahdi , Yazdani Nezhad Hamed
Published: August 2023

The development of efficient, energy‐saving, and automated manufacturing of free‐form variable‐thickness polymer composite components has created a step‐change and enabled technology for the composites industry seeking geometry tailoring during a mould‐less and/or additive manufacturing such as that in 3D printing. The current article presents research on magnetic field assisted 3D printing of iron particles‐embedded thermoplastic polylactic acid, during a fused deposition method based 3D printing. The magnets are symmetrically fixed on both sides of the printed nanocomposite. The setup utilised Neodymium magnets with a constant strength below one Tesla. Observations have shown that the nanocomposites being printed undergo permanent macro‐scale deformations due to the extrinsic strains induced by the iron particles' magnetisation. To provide a theoretical understanding of the induced strains, a Multiphysics constitutive equation has been developed. The evolution of magnetisation within a relatively thick nanocomposite (5 mm thickness) has been studied. A correlation has been established between the extrinsic strains from the experimental data and the theoretical solution. The theory exhibits an accurate description of the field‐induced strains provided that real‐time temperatures for the printed layers are accounted for. The results demonstrate a viable and disruptive magnetic field‐equipped fabrication with ability for permanent geometry control during a process.
Hypomethylation of DYRK4 in peripheral blood is associated with increased lung cancer risk
Authors: Qiao Rong , Zhu Qiang , Di Feifei , Liu Chunlan , Song Yakang , Zhang Jin , Xu Tian , Wang Yue , Dai Liping , Gu Wanjian , Han Baohui , Yang Rongxi
Published: August 2023

Lung cancer (LC) is the leading cause of cancer‐related deaths worldwide. It is urgent to identify new biomarkers for the early detection of LC. DNA methylation in peripheral blood has been reported to be associated with cancers. We conducted two independent case–control studies and a nested case–control study (168 LC cases and 167 controls in study Ⅰ, 677 LC cases and 833 controls in study Ⅱ, 147 precancers and 21 controls in the nested case–control study). The methylation levels of DYRK4 CpG sites were measured using mass spectrometry and their correlations with LC were analyzed by logistic regression and nonparametric tests. Bonferroni correction was used for the multiple comparisons. LC‐related decreased DYRK4 methylation was discovered in Study I and validated in Study II (the odds ratios [ORs] for the lowest vs. highest quartile of all three DYRK4 CpG sites ranged from 1.64 to 2.09, all p < 0.001). Combining the two studies, hypomethylation of DYRK4 was observed in stage I cases (ORs per −10% methylation ranged from 1.16 to 1.38, all p < 5.9E−04), and could be enhanced by male gender (ORs ranged from 1.77 to 4.17 via interquartile analyses, all p < 0.017). Hypomethylation of DYRK4_A_CpG_2 was significantly correlated with tumor size, length, and stage (p = 0.034, 0.002, and 0.002, respectively) in LC cases. Our study disclosed the association between DYRK4 hypomethylation in peripheral blood and LC, suggesting the feasibility of blood‐based DNA methylation as new biomarker for LC detection.
Condition and postrelease mortality of angled Northern Pike temporarily retained on stringers
Authors: Madden Jamie C. , LaRochelle Luc , Burton Declan , Danylchuk Andy J. , Landsman Sean J. , Cooke Steven J.
Published: August 2023

Objective

Anglers typically use stringers to keep fish intended for harvest from spoiling or for high-grading purposes (i.e., culling). However, relatively few studies have examined the effects of temporary stringer retention on the physical condition and postrelease mortality of fish. In this study, our objective was to investigate the lethal and sublethal effects of temporarily retaining Northern Pike Esox lucius on stringers.

Methods

We evaluated the blood physiology, reflex impairment, injury, and fate of 168 Northern Pike that were exposed for 2 h on one of five treatments: (1) cord stringer through the operculum, (2) cord stringer through the lower jaw, (3) metal stringer through the operculum, (4) metal stringer through the lower jaw, and (5) aerated tank control.

Result

Immediately after retention, blood lactate concentrations of stringer treatments were on average 42% greater relative to controls. Fish from the stringer treatments exhibited injuries of varying severity, most of which (e.g., gill lesions, expanded puncture wounds, swelling) were still present on surviving fish 48 h later. Reflexes were impaired for all stringer fish, whereas control fish tended to have all reflexes intact. No fish died during the treatment period. The highest occurrence of mortality was within the first 8 h following retention for the cord–operculum (48%), metal–jaw (15%), and metal–operculum (19%) treatments. Stringers placed through the operculum had a higher mortality rate (37%) compared with stringers placed through the lower jaw (17%), regardless of stringer type. Overall, 27% of fish placed on stringers died and 68% of the remaining fish showed injuries related to stringers, while control fish showed low mortality (7%) and no meaningful injuries.

Conclusion

Our results suggest that holding fish on stringers causes stress and injury levels that can result in postrelease mortality. As such, fisheries managers should consider restricting the release of fish placed on stringers, and once placed on a stringer, fish should be regarded as part of the daily harvest limit for a given angler.
Urinary incontinence‐related effects on functional connectivity circuits in persons with Parkinson's disease
Authors: Denmon Chanse , Wakeman Daniel G. , Vernon Mark , McGregor Keith , Krishnamurthy Venkatagiri , Krishnamurthy Lisa , Stevens Jennifer , Vaughan Camille P.
Published: August 2023

Introduction

Urinary incontinence (UI) is a common and disruptive symptom of Parkinson's disease (PD). This study aimed to identify neural correlates associated with UI among PD patients with UI (UI‐PD) compared to those PD patients without UI (nonUI‐PD) with the expectation of demonstrating increased functional connectivity (FC) between areas in the striatum and limbic system and decreased FC in executive areas.

Methods

rsfMRI and T1w data (n = 119) were retrieved from the Parkinson's Progression Markers Initiative (PPMI). Resting‐state FC analyses assessed temporal covariance with anterior cingulate gyrus, precuneus, and putamen seed regions.

Results

The UI‐PD group (n = 32, 16 females) showed significantly greater positive FC between the bilateral putamen seed and the right caudate and right thalamus (p < 0.01), relative to individuals with PD but who did not have UI (n = 87, 18 females). The UI‐PD group showed greater negative FC between the anterior cingulate seed and right angular gyrus (p < 0.01) relative to nonUI‐PD.

Conclusion

Individuals with PD and UI display stronger FC within neural circuits likely affected by PD such as between the putamen and caudate, as well as within those associated with brain bladder control, compared to persons with PD and without UI. Clinical application based on this study's results can provide greater discernment of treatment strategies for UI‐PD patients.
Universal generative modeling in dual domains for dynamic MRI
Authors: Yu Chuanming , Guan Yu , Ke Ziwen , Lei Ke , Liang Dong , Liu Qiegen
Published: August 2023

Dynamic magnetic resonance image reconstruction from incomplete k‐space data has generated great research interest due to its ability to reduce scan time. Nevertheless, the reconstruction problem remains a thorny issue due to its ill posed nature. Recently, diffusion models, especially score‐based generative models, have demonstrated great potential in terms of algorithmic robustness and flexibility of utilization. Moreover, a unified framework through the variance exploding stochastic differential equation is proposed to enable new sampling methods and further extend the capabilities of score‐based generative models. Therefore, by taking advantage of the unified framework, we propose a k‐space and image dual‐domain collaborative universal generative model (DD‐UGM), which combines the score‐based prior with a low‐rank regularization penalty to reconstruct highly under‐sampled measurements. More precisely, we extract prior components from both image and k‐space domains via a universal generative model and adaptively handle these prior components for faster processing while maintaining good generation quality. Experimental comparisons demonstrate the noise reduction and detail preservation abilities of the proposed method. Moreover, DD‐UGM can reconstruct data of different frames by only training a single frame image, which reflects the flexibility of the proposed model.
Development of 3D printable cenosphere‐reinforced polyethylene terephthalate glycol (PETG) filaments for lightweight structural applications
Authors: Kumar Jitendra , Negi Sushant
Published: August 2023

Present research evaluates the feasibility of producing polyethylene terephthalate glycol (PETG) filaments reinforced with cenosphere (CS), which have great potential to develop syntactic foam composites (SFC) for several applications, that is, from automotive to aerospace. A melt flow extrusion technique was used to reinforce PETG with different weight fractions (i.e., 0, 10, 20, 30, and 40 wt%) cenosphere, and further, the thermal, mechanical, and physical properties of the prepared feedstocks were investigated in detail. Results indicated that Young's modulus, load‐bearing capacity, and ultimate tensile strength of PETG filament with 40 wt% CS were 1652.1 5 MPa, 76.91 1 N, and 31.97 1 MPa, respectively, which is similar to virgin PETG filament. In addition, the porosity of the CS‐reinforced PETG filaments decreased with increasing concentration of the CS in the PETG matrix. Such cenosphere‐filled filaments possess attractive thermo‐mechanical and physical properties to develop high‐quality SFC through additive manufacturing (AM) routine.

Highlights

PETG/cenosphere based 3D printing filaments were developed.

The modulus and strength significantly improved by adding 40% cenosphere.

The porosity decreased with increasing cenosphere weight fraction.

Addition of cenosphere affected water absorption characteristics of filaments.
Machine learning‐assisted study of correlation between post‐transition‐state bifurcation and initial phase information at the ambimodal transition state
Authors: Murakami Tatsuhiro , Kikuma Yuya , Ibuki Shunichi , Matsumoto Naoki , Ogino Kanon , Hashimoto Yu , Takayanagi Toshiyuki
Published: August 2023

The Diels–Alder cycloaddition of cyclopentadiene and nitroethene, the intramolecular cycloaddition between a diene and triene, and the Diels–Alder cycloaddition of 2‐hydroxyacrolein with 1,3‐butadiene involving post‐transition‐state bifurcation (PTSB) were studied. These cycloaddition reactions were investigated using quasi‐classical trajectory (QCT), classical molecular dynamics (MD), ring‐polymer molecular dynamics (RPMD) simulations, and supervised machine‐learning binary classification techniques. Room‐temperature dynamics simulations started from the ambimodal transition state (TS) using the QCT, classical MD, and RPMD methods presented similar dynamics. Binary classification revealed that the initial geometry displacement from the ambimodal TS for the Diels–Alder cycloaddition of cyclopentadiene and nitroethene contributed to the branching dynamics and that the initial momenta for the intramolecular cycloaddition between a diene and triene and the Diels–Alder cycloaddition of 2‐hydroxyacrolein with 1,3‐butadiene played a significant role in the bifurcation dynamics.
Changing cancer mindsets: A randomized controlled feasibility and efficacy trial
Authors: Zion Sean R. , Schapira Lidia , Berek Jonathan S. , Spiegel David , Dweck Carol S. , Crum Alia J.
Published: August 2023

Objective

A cancer diagnosis and subsequent treatment can disrupt the full spectrum of physical, social, emotional, and functional quality of life. But existing psychological treatments are focused primarily on specific psychological symptoms as opposed to improving the overall patient experience. We studied the feasibility and efficacy of a novel digital intervention targeting patient mindsets—core assumptions about the nature and meaning of illness—designed to improve overall health‐related quality of life (HRQoL) in newly diagnosed cancer patients undergoing treatment with curative intent.

Methods

Recently diagnosed (≤150 days) adult patients with non‐metastatic cancers undergoing systemic treatment (N = 361) were recruited from across the United States to participate in this decentralized clinical trial. Patients were randomized 1:1 to receive the Cancer Mindset Intervention (CMI) or Treatment as Usual (TAU). Participants in the CMI group completed seven online modules over 10 weeks (2.5 h total) targeting mindsets about cancer and the body. The primary outcome was overall HRQoL, and secondary outcomes were coping behaviors and symptom distress.

Results

Patients in the CMI group reported significant (p < 0.001) improvements in adaptive mindsets about cancer and the body over time. Compared with the TAU condition, the CMI group reported significant improvements in overall HRQoL (B = 0.60; 95% CI 0.34–0.85; p < 0.001), increased engagement in adaptive coping behaviors (B = 0.03; 95% CI 0.02–0.04; p < 0.001), and reduced distress from physical symptoms (B = −0.29; 95% CI −0.44 to −0.14; p < 0.01). Effect sizes of these changes ranged from d = 0.42–d = 0.54.

Conclusion

A brief mindset‐focused digital intervention was effective at improving physical, social, emotional, and functional HRQoL, increasing adaptive coping behaviors, and reducing physical symptom distress in newly diagnosed cancer patients.
Evaluation of the SIMULRESP: A simulation software of child and teenager cardiorespiratory physiology
Authors: Brossier David , Flechelles Olivier , Sauthier Michael , Engert Catherine , Chahir Youssef , Emeriaud Guillaume , Cheriet Farida , Jouvet Philippe , de Montigny Simon
Published: August 2023

Background

Mathematical models based on the physiology when programmed as a software can be used to teach cardiorespiratory physiology and to forecast the effect of various ventilatory support strategies. We developed a cardiorespiratory simulator for children called “SimulResp.” The purpose of this study was to evaluate the quality of SimulResp.

Methods

SimulResp quality was evaluated on accuracy, robustness, repeatability, and reproducibility. Blood gas values (pH, PaCO2, PaO2, and SaO2) were simulated for several subjects with different characteristics and in different situations and compared to expected values available as reference. The correlation between reference and simulated data was evaluated by the coefficient of determination and Intraclass correlation coefficient. The agreement was evaluated with the Bland & Altman analysis.

Results

SimulResp produced healthy child physiological values within normal range (pH 7.40 ± 0.5; PaCO2 40 ± 5 mmHg; PaO2 90 ± 10 mmHg; SaO2 97 ± 3%) starting from a weight of 25−35 kg, regardless of ventilator support. SimulResp failed to simulate accurate values for subjects under 25 kg and/or affected with pulmonary disease and mechanically ventilated. Based on the repeatability was considered as excellent and the reproducibility as mild to good. SimulResp's prediction remains stable within time.

Conclusions

The cardiorespiratory simulator SimulResp requires further development before future integration into a clinical decision support system.
Sonographic assessment of diaphragmatic thickness and excursion to predict CPAP failure in neonates below 34 weeks of gestation: A prospective cohort study
Authors: Gupta Rashi , Bandyopadhyay Tapas , Yadav Bharti , Guleria Munish , Maria Arti
Published: August 2023

Background

To evaluate the diagnostic accuracy of sonographic assessment of diaphragmatic dimensions and excursions in predicting Continuous Positive Airway Pressure (CPAP) failure in preterm neonates with respiratory distress.

Methods

Prospective cohort study among preterm neonates less than 34 weeks of gestation who were hemodynamically stable and either admitted with respiratory distress or who developed respiratory distress shortly after admission to the NICU and having Silverman‐Anderson Score (SAS) ≥ 3/10 were included. We performed sonographic assessment of diaphragmatic dimensions and excursions before and one hour ±30 minutes after application of CPAP. ‘CPAP failure’ was defined as combined outcome of the need of surfactant and/or upgradation of respiratory support within first 72 hours after a trial of CPAP. Clinical parameters and diaphragmatic measurements were compared between CPAP failure and success groups.

Results

Of 62 participants, 20 (32%) failed CPAP. On binomial logistic regression (after adjustment for gestational age and birth weight), initial SAS, higher diaphragmatic excursion (both left and right, before and after CPAP application), lower left hemidiaphragm diaphragmatic thickness fraction (DTF) (before CPAP application) and lower right DTF (after CPAP application) were independent predictors of CPAP failure. However, the receiver‐operating characteristics curves showed that excursions of right and left hemi‐diaphragm both before and after CPAP application, had highest accuracies in predicting CPAP failure (AUC 0.84, 0.80 and 0.86, 0.78, respectively; p < .001).

Conclusion

Diaphragmatic excursion can be a useful parameter to predict the failure of CPAP in preterm neonates with respiratory distress.
Can a propensity score matching method be applied to assessing efficacy from single‐arm proof‐of‐concept trials in oncology?
Authors: Teng Shu‐Wen , Su Yu‐Cheng , Pallantla Ravikumar , Channavazzala Madhav , Kumar Rukmini , Sheng Yucheng , Wang Hao , Wang Crystal , Tse Archie
Published: August 2023

As a result of the escalating number of new cancer treatments being developed and competition among pharmaceutical companies, decisions regarding how to proceed with phase III trials are frequently based on findings from either single‐arm phase I expansion cohorts or phase II studies that compare the efficacy of the study drug to a standard‐of‐care benchmark derived from historical data. However, even when eligibility criteria are matched, differences in the distribution of baseline patient features may influence the outcome of single‐arm trials in real‐world scenarios. Therefore, novel methods are needed to enhance the accuracy of efficacy prediction from current cohorts relative to historical data. In this study, we demonstrated the feasibility of using the propensity score matching (PSM) method to improve decision making by matching relevant baseline features between current and historical cohorts. According to our findings, utilizing the PSM method may provide a less biased means of comparing outcomes between current and historical cohorts relative to a naïve approach, which relies solely on differences in average outcomes between the cohorts.
Saffron (Crocus sativus) and its constituents for pain management: A review of current evidence
Authors: Pourbagher‐Shahri Ali Mohammad , Forouzanfar Fatemeh
Published: August 2023

Pain can become a chronic and deliberating experience with a significant burden. In preclinical and clinical studies, Saffron (Crocus sativus L.) has shown analgesic activities. Considering the unsatisfactory results of current therapeutic management for chronic pain conditions, we aimed to review saffron's analgesic activity and underlying mechanisms. Saffron showed antinociceptive activities in formalin‐, carrageenan‐, and capsaicin‐induced experimental pain models. Saffron analgesic activities affected several targets, including ion channels of nociceptors; the adrenergic system and central histaminic system; inhibition of inflammatory pathways, apoptotic pathways, and oxidative stress; regulation of NO pathway, and the endocannabinoid system. Clinical studies showed analgesia of Saffron in rheumatoid arthritis, after‐pain following childbirth, dysmenorrhea, and fibromyalgia. Our literature review showed that saffron can be beneficial as an adjunct therapy to commonly used analgesics in practice, particularly in chronic pain conditions.
An outlook on the target‐based molecular mechanism of phytoconstituents as immunomodulators
Authors: Noor Gazala , Badruddeen  , Akhtar Juber , Singh Bhuwanendra , Ahmad Mohammad , Khan Mohammad Irfan
Published: August 2023

The immune system is one of the essential defense mechanisms. Immune system inadequacy increases the risk of infections and cancer diseases, whereas over‐activation of the immune system causes allergies or autoimmune disorders. Immunomodulators have been used in the treatment of immune‐related diseases. There is growing interest in using herbal medicines as multicomponent agents to modulate the complex immune system in immune‐related diseases. Many therapeutic phytochemicals showed immunomodulatory effects by various mechanisms. This mechanism includes stimulation of lymphoid cell, phagocytosis, macrophage, and cellular immune function enhancement. In addition increased antigen‐specific immunoglobulin production, total white cell count, and inhibition of TNF‐α, IFN‐γ, NF‐kB, IL‐2, IL‐6, IL‐1β, and other cytokines that influenced the immune system. This review aims to overview, widely investigated plant‐derived phytoconstituents by targeting cells to modulate cellular and humoral immunity in in vivo and in vitro. However, further high‐quality research is needed to confirm the clinical efficacy of plant‐based immunomodulators.
Optimal bisections of directed graphs
Authors: Liu Guanwu , Ma Jie , Zu Chunlei
Published: August 2023

In this article, motivated by a problem of Scott [Surveys in combinatorics, 327 (2005), 95‐117.] and a conjecture of Lee et al. [Random Struct. Algorithm, 48 (2016), 147‐170.] we consider bisections of directed graphs. We prove that every directed graph with arcs and minimum semidegree at least admits a bisection in which at least arcs cross in each direction. This provides an optimal bound as well as a positive answer to a question of Hou and Wu [J. Comb. Theory B, 132 (2018), 107‐133.] in a stronger form.
Hypothesis testing procedure for binary and multi‐class F1‐scores in the paired design
Authors: Takahashi Kanae , Yamamoto Kouji , Kuchiba Aya , Shintani Ayumi , Koyama Tatsuki
Published: August 2023

In modern medicine, medical tests are used for various purposes including diagnosis, disease screening, prognosis, and risk prediction. To quantify the performance of the binary medical test, we often use sensitivity, specificity, and negative and positive predictive values as measures. Additionally, the ‐score, which is defined as the harmonic mean of precision (positive predictive value) and recall (sensitivity), has come to be used in the medical field due to its favorable characteristics. The ‐score has been extended for multi‐class classification, and two types of ‐scores have been proposed for multi‐class classification: a micro‐averaged ‐score and a macro‐averaged ‐score. The micro‐averaged ‐score pools per‐sample classifications across classes and then calculates the overall ‐score, whereas the macro‐averaged ‐score computes an arithmetic mean of the ‐scores for each class. Additionally, Sokolova and Lapalme gave an alternative definition of the macro‐averaged ‐score as the harmonic mean of the arithmetic means of the precision and recall over classes. Although some statistical methods of inference for binary and multi‐class ‐scores have been proposed, the methodology development of hypothesis testing procedure for them has not been fully progressing yet. Therefore, we aim to develop hypothesis testing procedure for comparing two ‐scores in paired study design based on the large sample multivariate central limit theorem.
A guide to regression discontinuity designs in medical applications
Authors: Cattaneo Matias D. , Keele Luke , Titiunik Rocío
Published: August 2023

We present a practical guide for the analysis of regression discontinuity (RD) designs in biomedical contexts. We begin by introducing key concepts, assumptions, and estimands within both the continuity‐based framework and the local randomization framework. We then discuss modern estimation and inference methods within both frameworks, including approaches for bandwidth or local neighborhood selection, optimal treatment effect point estimation, and robust bias‐corrected inference methods for uncertainty quantification. We also overview empirical falsification tests that can be used to support key assumptions. Our discussion focuses on two particular features that are relevant in biomedical research: (i) fuzzy RD designs, which often arise when therapeutic treatments are based on clinical guidelines, but patients with scores near the cutoff are treated contrary to the assignment rule; and (ii) RD designs with discrete scores, which are ubiquitous in biomedical applications. We illustrate our discussion with three empirical applications: the effect CD4 guidelines for anti‐retroviral therapy on retention of HIV patients in South Africa, the effect of genetic guidelines for chemotherapy on breast cancer recurrence in the United States, and the effects of age‐based patient cost‐sharing on healthcare utilization in Taiwan. Complete replication materials employing publicly available data and statistical software in Python, R and Stata are provided, offering researchers all necessary tools to conduct an RD analysis.
Unified semicompeting risks analysis of hepatitis natural history through mediation modeling
Authors: Yu Jih‐Chang , Huang Yen‐Tsung
Published: August 2023

Natural history of hepatitis B or C is comprised of multiple milestones such as liver cirrhosis and liver cancer. To fully characterize its natural course, semicompeting risks represent a common problem where liver cirrhosis and liver cancer are both of interest, but only the former may be censored by the latter. Copula, frailty and multistate models serve as well‐established analytics for semicompeting risks. Here, we cast the semicompeting risks in a mediation framework, with liver cirrhosis as a mediator and liver cancer as an outcome. We define the indirect and direct effects as the effects of an exposure on the liver cancer incidence mediated and not mediated through liver cirrhosis, respectively. With the estimands derived as conditional probabilities, we derive respective expressions under the copula, frailty, and multistate models. Next, we propose estimators based on nonparametric maximum likelihood orU‐statistics and establish their asymptotic results. Numerical studies demonstrate that the efficiency of copula models leads to potential bias due to model misspecification. Moreover, the robustness of frailty models is accompanied by a loss in efficiency, and multistate models balance the efficiency and robustness. We demonstrate the utility of the proposed methods by a hepatitis study, showing that hepatitis B and C lead to a higher incidence of liver cancer by increasing liver cirrhosis incidence. Thus, mediation modeling provides a unified framework that accommodates various semicompeting risks models.