bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid Prototyping for Accelerated Establishment of Film Processing‐Performance Relationships in Silicon Phthalocyanine OFETs
Authors: Cranston Rosemary R. , Mauthe Jacob , Wang Tonghui , Thapa Gaurab J. , Amassian Aram , Lessard Benoît H.
Published: November 2024

Understanding the complex relationships underlying the performance of organic electronic devices, such as organic field‐effect transistors (OFETs), requires researchers to navigate a multi‐dimensional parameter space that includes material design, solution formulation, fabrication parameters, and device geometry. Herein, a recently developed materials acceleration platform is demonstrated, named the RoboMapper, to perform direct on‐chip fabrication of OFETs by ultrasonic meniscus printing using silicon phthalocyanine (SiPc) derivatives as the semiconductor. OFETs using bis(tri‐n‐butylsilyl oxide) SiPc ((3BS)2‐SiPc) exhibited the best device performance characterized by the highest electron field‐effect mobility (µe). Through optical microscopy and grazing‐incidence wide‐angle X‐ray scattering (GIWAXS), the favorable performance of (3BS)2‐SiPc is attributed to the specific film morphology and molecular packing achieved with optimal print conditions. Investigating the impact of deposition parameters reveals the crucial role of solvent evaporation rate and print speed in achieving high‐quality film formation. Overall, optimal fabrication conditions for (3BS)2‐SiPc devices include slow print speeds and fast evaporating solutions achieved by using a mixture of co‐solvents and an elevated substrate temperature. The results of this work reveal distinct relationships between deposition conditions, film properties, and device performance for each SiPc derivative and emphasize the necessity of high throughput experimentation to comprehensively understand process‐performance relationships in organic semiconductors.
Phosphoproteomic analysis of distylous Turnera subulata identifies pathways related to endoreduplication that correlate with reciprocal herkogamy
Authors: Henning Paige M. , Minkoff Benjamin B. , Sussman Michael R.
Published: November 2024

Premise

A multi‐omic approach was used to explore proteins and networks hypothetically important for establishing filament dimorphisms in heterostylous Turnera subulata (Sm.) as an exploratory method to identify genes for future empirical research.

Methods

Mass spectrometry (MS) was used to identify differentially expressed proteins and differentially phosphorylated peptides in the developing filaments between the L‐ and S‐morphs. RNAseq was used to generate a co‐expression network of the developing filaments, MS data were mapped to the co‐expression network to identify hypothetical relationships between the S‐gene responsible for filament dimorphisms and differentially expressed proteins.

Results

Mapping all MS identified proteins to a co‐expression network of the S‐morph's developing filaments identified several clusters containing SPH1 and other differentially expressed or phosphorylated proteins. Co‐expression analysis clustered CDKG2, a protein that induces endoreduplication, and SPH1—suggesting a shared biological function. MS analysis suggests that the protein is present and phosphorylated only in the S‐morph, and thus active only in the S‐morph. A series of CDKG2 regulators, including ATM1, and cell cycle regulators also correlated with the presence of reciprocal herkogamy, supporting our interest in the protein.

Conclusions

This work has built a foundation for future empirical work, specifically supporting the role of CDKG2 and ATM1 in promoting filament elongation in response to SPH1 perception.
Mini‐consolidations or intermediate‐dose cytarabine for the post‐remission therapy of AML patients over 60. A retrospective study from the DATAML and SAL registries
Authors: Récher Christian , Dumas Pierre‐Yves , Bérard Emilie , Tavitian Suzanne , Leguay Thibaut , Galtier Jean , Alric Camille , Bidet Audrey , Delabesse Eric , Rieu Jean Baptiste , Vial Jean‐Philippe , Vergez François , Luquet Isabelle , Klein Emilie , de Grande Anne‐Charlotte , Sarry Audrey , Zukunft Sven , Platzbecker Uwe , Müller‐Tidow Carsten , Baldus Claudia D. , Bornhäuser Martin , Serve Hubert , Bertoli Sarah , Pigneux Arnaud , Röllig Christoph
Published: November 2024

According to current recommendations, older AML patients in first complete remission (CR) after induction chemotherapy should receive consolidation with intermediate‐dose cytarabine (IDAC). However, no study has demonstrated the superiority of IDAC over other regimen. In this retrospective study, we compared the efficacy of mini‐consolidations (idarubicin 8 mg/m2 day 1, cytarabine 50 mg/m2/12 h, day 1–5) and IDAC. Inclusion criteria were newly diagnosed AML, age > 60 years, first CR after induction and at least 1 cycle of consolidation. Of the 796 included patients, 322 patients received mini‐consolidations and 474 patients received IDAC. Mini‐consolidation patients were older, and more often, they had de novo AML and unfavorable risk. The rate of allogeneic transplantation was higher in the IDAC group. The median number of cycles was higher in the mini‐consolidation group (4 vs. 2; p < .0001). Median relapse‐free survival was 18 months with mini‐consolidations and 12 months with IDAC (p = .0064). In multivariate analysis, the risk of relapse or death was significantly higher in the IDAC group (p = .004). Median OS was 36 versus 31 months with mini‐consolidations or IDAC, respectively (p = .46). In multivariate analysis, the consolidation regimen had no significant influence on OS (p = .43). In older AML patients, post‐remission therapy with mini‐consolidations represents an alternative to IDAC.
The Glu86 Residue in TBX4 Proves Critical for Human Lung Development
Authors: Szafranski Przemyslaw , Gambin Tomasz , Deutsch Gail , Nassef Salma A. , Bailey Mary Clay , Kearney Debra L. , Stankiewicz Paweł
Published: November 2024

T‐box transcription factors are a group of evolutionarily conserved T‐box‐containing regulators of mesoderm specification and development. Heterozygous single nucleotide variants (SNVs) or copy‐number variant (CNV) deletions involving dosage‐sensitive TBX4 have been associated with pulmonary arterial hypertension (PAH), ischiocoxopodopatellar syndrome with or without PAH, and lethal lung developmental disorders (LLDDs), including acinar dysplasia (AcDys), congenital alveolar dysplasia (CAD), and other unspecified primary pulmonary hypoplasias. Loss‐ and gain‐of‐function variants have been proposed to cause pediatric PAH and LLDDs, and adult forms of PAH, respectively. Of more than 50 missense SNVs scattered across the entire TBX4, only three have been reported in patients with LLDDs, all mapping to the T‐box domain. Here, we report a recurrence of a pathogenic substitution Glu86Lys identified in an unrelated patient with AcDys. In silico predictions of the conformational changes of TBX4 resulting from this and another substitution, Glu86Gln, suggest the loss of most intermolecular hydrogen bonds involving residue 86, including those with Tyr230 that directly interact with DNA. Functional assays on the TBX4 variants in fetal lung fibroblasts confirmed their deleterious character. We propose that Glu86 is critically involved in maintaining TBX4 structure and function essential for airway branching during early stages of human lung development. Substitutions of this residue may act in a dominant negative manner, leading to AcDys and CAD.
TEMPO‐Mediated Cross‐Dehydrogenative Coupling for the Synthesis of Bis(indolyl)methanes
Authors: Guo You‐Qiang , Liang Long , Wang Zhen‐Yu , Wu Xiang , Li You‐Gui
Published: November 2024

A TEMPO‐mediated method has been developed for the synthesis of bis(indolyl)‐methane derivatives by the cross‐dehydrogenative coupling between C(sp3)−H of para‐cresol derivatives and C(sp2)−H of indoles in moderate yields under aqueous conditions. This method utilizes toluene derivatives as starting materials, allowing for coupling without the need for further functionalization. The use of environmentally friendly water as a solvent minimizes waste generation. Electron‐donating groups such as methyl and methoxy, as well as halogens like fluorine, chlorine, and bromine, exhibit good tolerance in this process. Furthermore, a possible reaction mechanism is proposed to elucidate the formation of BIMs.
Optimization of Reaction Conditions for On‐DNA Synthesis of Ureas, Thioureas, and Sulfonamides
Authors: Migliorini Francesca , Ciamarone Andrea , Neri Dario , Cazzamalli Samuele , Favalli Nicholas
Published: November 2024

Isocyanates, isothiocyanates, and sulfonyl chlorides can be found in valuable building blocks for the construction of DNA‐Encoded Chemical Libraries (DELs), leading to the generation of ureas, thioureas, and sulfonamides. We present the development of reaction conditions for the addition of isocyanates, isothiocyanates, and sulfonyl chlorides to single‐stranded oligonucleotides, with a focus on maximizing on‐DNA conversion while preserving DNA integrity. We explored and optimized reaction parameters to achieve efficient coupling and minimize DNA degradation and by‐product formation. The protocols reported in this paper broaden the scope of DNA‐compatible reactions and may be applicable to the construction of novel DELs.
N‐Heterocyclic Carbene Catalyzed Activation of Carboxylic Acids
Authors: Qin Yueling , Li Tingting
Published: November 2024

N‐heterocyclic carbene (NHC) catalyzed reactions of carboxylic acids play a crucial role in NHC catalysis, enabling the formation of chiral and achiral functional molecules. In this review, the achievements in NHC catalyzed activations of carboxylic acids are summarized, and an outlook on future research directions is also provided.
Cerebrovascular Function in Sporadic and Genetic Cerebral Small Vessel Disease
Authors: Stringer Michael S. , Blair Gordon W. , Kopczak Anna , Kerkhofs Danielle , Thrippleton Michael J. , Chappell Francesca M. , Maniega Susana Muñoz , Brown Rosalind , Shuler Kirsten , Hamilton Iona , Garcia Daniela Jaime , Doubal Fergus N. , Clancy Una , Sakka Eleni , Poliakova Tetiana , Janssen Esther , Duering Marco , Ingrisch Michael , Staals Julie , Backes Walter H. , van Oostenbrugge Robert , Biessels Geert Jan , Dichgans Martin , Wardlaw Joanna M. ,   The SVDs@target consortium
Published: November 2024

Objective

Cerebral small vessel diseases (SVDs) are associated with cerebrovascular dysfunction, such as increased blood–brain barrier leakage (permeability surface area product), vascular pulsatility, and decreased cerebrovascular reactivity (CVR). No studies assessed all 3 functions concurrently. We assessed 3 key vascular functions in sporadic and genetic SVD to determine associations with SVD severity, subtype, and interrelations.

Methods

In this prospective, cross‐sectional, multicenter INVESTIGATE‐SVDs study, we acquired brain magnetic resonance imaging in patients with sporadic SVD/cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), including structural, quantitative microstructural, permeability surface area product, blood plasma volume fraction, vascular pulsatility, and CVR (in response to CO2) scans. We determined vascular function and white matter hyperintensity (WMH) associations, using covariate‐adjusted linear regression; normal‐appearing white matter and WMH differences, interrelationships between vascular functions, using linear mixed models; and major sources of variance using principal component analyses.

Results

We recruited 77 patients (45 sporadic/32 CADASIL) at 3 sites. In adjusted analyses, patients with worse WMH had lower CVR (B = −1.78, 95% CI −3.30, −0.27) and blood plasma volume fraction (B = −0.594, 95% CI −0.987, −0.202). CVR was worse in WMH than normal‐appearing white matter (eg, CVR: B = −0.048, 95% CI −0.079, −0.017). Adjusting for WMH severity, SVD subtype had minimal influence on vascular function (eg, CVR in CADASIL vs sporadic: B = 0.0169, 95% CI −0.0247, 0.0584). Different vascular function mechanisms were not generally interrelated (eg, permeability surface area product~CVR: B = −0.85, 95% CI −4.72, 3.02). Principal component analyses identified WMH volume/quantitative microstructural metrics explained most variance in CADASIL and arterial pulsatility in sporadic SVD, but similar main variance sources.

Interpretation

Vascular function was worse with higher WMH, and in WMH than normal‐appearing white matter. Sporadic SVD‐CADASIL differences largely reflect disease severity. Limited vascular function interrelations may suggest disease stage‐specific differences. ANN NEUROL 2025;97:483–498
Micro‐Doses of DNP Preserve Motor and Muscle Function with a Period of Functional Recovery in Amyotrophic Lateral Sclerosis Mice
Authors: Zhong Renjia , Dionela Demi L.A. , Kim Nina Haeyeon , Harris Erin N. , Geisler John G. , Wei‐LaPierre Lan
Published: November 2024

Objective

Mitochondrial dysfunction is one of the earliest pathological events observed in amyotrophic lateral sclerosis (ALS). The aim of this study is to evaluate the therapeutic efficacy of 2,4‐dinitrophenol (DNP), a mild mitochondrial uncoupler, in an ALS mouse model to provide preclinical proof‐of‐concept evidence of using DNP as a potential therapeutic drug for ALS.

Methods

hSOD1G93A mice were treated with 0.5–1.0 mg/kg DNP through daily oral gavage from presymptomatic stage or disease onset until 18 weeks old. Longitudinal behavioral studies were performed weekly or biweekly from 6 to 18 weeks old. In situ muscle contraction measurements in extensor digitorum longus muscles were conducted to evaluate the preservation of contractile force and motor unit numbers in hSOD1G93A mice following DNP treatment. Muscle innervation and inflammatory markers were assessed using immunostaining. Extent of protein oxidation and activation of Akt pathway were also examined.

Results

DNP delayed disease onset; improved motor coordination and muscle performance in vivo; preserved muscle contractile function, neuromuscular junction morphology, and muscle innervation; and reduced inflammation and protein oxidation at 18 weeks old in hSOD1G93A mice. Strikingly, symptomatic hSOD1G93A mice exhibited a period of recovery in running ability at 20 cm/s several weeks after 2,4‐dinitrophenol treatment started at disease onset, offering the first observation in disease phenotype reversal using a small molecule.

Interpretation

Our results strongly support that micro‐dose DNP may be used as a potential novel treatment for ALS patients, with a possibility for recovery, when used at optimal doses and time of intervention. ANN NEUROL 2025;97:542–557
Study on the Structure and Function of Intestinal Microorganisms in Silkworm Maggot Exorista sorbillans
Authors: Zhong Siyin , Jiang Zhe , Zhang Jiabao , Gu Zhiya , Wei Jing , Li Bing , Li Fanchi
Published: November 2024

Insects have important symbiotic relationships with their intestinal microbiota. The intestinal microbiota is involved in or influences various processes in insects such as development, metabolism, immunity, and reproduction. Currently, research on the intestinal microbiota of parasitic insects is still in its early stages. The tachinid parasitoid Exorista sorbillans is a dipteran parasitic insect, with the silkworm (Bombyx mori) being its main host. Silkworms parasitized by E. sorbillans can suffer from severe silkworm maggot disease, which also poses a serious threat to sericulture. In this study, the intestinal microbiota of larval E. sorbillans at three instar stages was analyzed using 16S rRNA amplicon sequencing to explore the community composition of the intestinal microbiota. Additionally, using conventional culture methods, six cultivable strains were isolated and identified from the larval E. sorbillans on an antibiotic‐free LB medium, and four cultivable strains were isolated and identified from the hemolymph of parasitized silkworms. This study investigated the E. sorbillans from the perspective of intestinal microbiota, elucidating the composition and structural characteristics of the intestinal microbiota of the tachinid parasitoid, and preliminarily discussing the functional roles of several major microorganisms, which helps to further clarify the potential mechanisms of interaction between the parasitoid and the silkworm.
Autism Spectrum and gastrointestinal health: Screening on the influence of environmental factors on gastrointestinal problems
Authors: Brito Anita , Tocantins Fernando Ribeiro , Brentani Helena , Fujita André , Taddei Carla Romano , Beltrão‐Braga Patricia Cristina Baleeiro
Published: November 2024

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that combines genetic and environmental factors. The human microbiota is colonized by permanent or transitory microorganisms, depending on the host and the external factors controlling their permanence. The composition of the gut microbiota (GM) in ASD individuals is notably different from that in controls, which may contribute to the clinical conditions observed in these individuals. This study aimed to indirectly investigate the influence of GM on the gut‐brain axis in individuals with ASD and controls by analyzing environmental factors that contribute to the microbiota composition. Two questionnaires were designed to collect data, one for the ASD Group (ASDG) and the other one for the Control Group (CG). The raw data from both questionnaires were collected from 2772 respondents. After triage, answers from 1687 ASD individuals, along with 466 respondents from the CG, were analyzed, resulting in a total of 2237 respondents. Our results showed that gastrointestinal problems (GP) escalate as individuals age and become more prominent in ASD individuals. In contrast, feeding problems (FP) did not appear to escalate in either group as individuals aged, even though the FP decreased in the CG. ANOVA revealed significant differences in breastfeeding status compared to GPs among preterm control individuals born via cesarean section (p‐value = 0.027). The mean values of GP for breastfed and nonbreastfed individuals, for ASDG (0.257; 0.268) and CG (0.105; 0.248), highlighted the differences in breastfeeding effects on GP for the study groups. The use of antibiotics during pregnancy seemed to be significant for GPs in the ASDG only for breastfed individuals (p‐value <0.001), but not in the CG group. In conclusion, variables such as mode of delivery, FPs, type of birth, and length of breastfeeding do not seem to be determining factors for GP in the ASDG but are relevant for the CG. However, for ASDG individuals whose mothers took antibiotics during pregnancy, breastfeeding may act as a protective factor, as maternal antibiotic administration during pregnancy seems to aggravate GP‐values across the ages of the participants. Considering GP as a proxy for GM and recognizing the importance of GM composition for central nervous system (CNS) function, it appears that in individuals with ASD, GM seems to be more dependent on other factors, which might be linked to the genetic background of each one. These findings suggest that future studies of the gut‐brain axis in individuals with ASD might consider the individual's genetic background, environmental factors, and GM.
Offending and clinical characteristics of adults with autism spectrum disorder: Experience at forensic psychiatry center in Türkiye between 2012 and 2022
Authors: Boylu Muhammed Emin , Görmez Aynur , Turan Şenol , Yeşilkaya Ümit Haluk , Boylu Fatma Betül , Duran Alaattin
Published: November 2024

The forensic and clinical need for better understanding of criminal offending in adults with ASD is increasingly recognized. To date, few studies have examined the differences and similarities between criminal offenders with and without ASD with respect to demographics, offending profiles, and clinical characteristics. This study, conducted in Turkey, is the first to conduct such as comparison using a national database of forensic files. Computerized search of the forensic records of 11,853 adults assessed between January 1, 2012, and January 1, 2022, for criminal responsibility by the Turkish Council of Forensic Medicine found 74 adults diagnosed with ASD; they ranged in age from 18 to 40. [Correction added after first online publication on 04 December 2024. The value 11,583 has been revised to 11,853.] The demographic, clinical, and offending characteristics of these adults were compared to 100 adults without ASD selected from the remaining 11,779 records based on age (18–40 years) and year of assessment (10 from each year). The ASD group was younger, more likely to be unemployed and not living on their own. The ASD group was more likely to have co‐morbid intellectual disability, ADHD, and OCD, while the non‐ASD group was more likely to have co‐morbid personality disorders, The ASD group was more likely to commit unplanned simple (non‐penetrative) sexual and violent offenses against strangers; the non‐ASD group was more likely to commit planned, qualified (penetrative) crimes against known persons. Impulsivity and manipulability were more often contributory in persons with ASD; revenge was more often contributory in persons without ASD. Adults with ASD were more likely to commit crimes on social media. In conclusion, this study found that adult offenders with and without ASD differed in demographics, psychiatric co‐morbidities, and types of offending behaviors. These differences may have implications for the prevention of criminal offending in persons with ASD and addressing their needs once they are in the criminal justice system.
Turning trash into treasure: conversion of agroresidue rice straw into carboxymethylcellulose biopolymer
Authors: Kaur Prabhpreet , Bohidar Himadri B. , Williams Richard , Pfeffer Frederick M. , Agrawal Ruchi
Published: November 2024

In the present study, rice straw‐derived cellulose was converted into carboxymethylcellulose (CMC) using alkalization followed by an etherification reaction. The synthesis conditions for this chemical modification were optimized such that CMC with a high degree of substitution (1.02) was obtained. Infrared spectra of the synthesized CMC clearly showed an increased intensity of the C═O bond at 1600 cm−1, confirming successful carboxymethylation. Further, X‐ray diffraction analysis demonstrated a decrease in cellulose crystallinity owing to partial rearrangement from a crystalline to an amorphous phase during initial alkalization reaction. The obtained CMC biopolymer was subsequently cross‐linked to form a composite hydrogel matrix reinforced with bentonite clay. The hydrogel showed about 91% adsorption capacity for methylene blue dye as a model contaminant in aqueous media. Therefore, this study shows that lignocellulosic agrowaste is a rich source of cellulose, and its derivatives such as CMC possess the potential to realize the waste to wealth sustainability goal.
Sequential Adaptive Design Method for Incorporating External Data
Authors: Chen Jinmei , Li Lixin , Feng Yuhao , Chow Shein‐Chung , Tan Ming , Pan Jianhong , Chen Pingyan , Wu Ying
Published: November 2024

External data (e.g., real‐world data (RWD) and historical data) have become more readily available. This has led to rapidly increasing interest in exploring and evaluating ways of utilizing external data to facilitate traditional clinical trials (TCT), especially for rare diseases with high unmet medical needs where a TCT would be impractical and/or unethical. In this article, we focus on hybrid studies that incorporate external data into randomized clinical trials to augment the control arm and explore a complex innovative design. A sequential adaptive design conducts multiple interim assessments to improve the accuracy of estimates of agreement between external data and current data. At each interim assessment, we apply the inverse probability weighted power prior (IPW‐PP) method to adaptively borrow information from external data to account for confounding and heterogeneity. The randomization ratio is dynamically adjusted during the interim assessment based on accumulatively augmented information to reduce the sample size of the current trial. Additionally, the proposed design can be extended to allow interim analyses for early efficacy/futility stopping, that is, early assessment of trial success or failure based on accumulated data, potentially reducing ineffective treatment exposure and unnecessary time and resources. The performance of the proposed method and design is evaluated via extensive simulation studies. The sequential adaptive design and IPW‐PP approach having desirable properties are implemented.
Addressing Class Imbalance in Bayesian Classification Through Posterior Probability Adjustment
Authors: Nassiri Vahid , Tekle Fetene , Tatikola Kanaka , Geys Helena
Published: November 2024

Class imbalance is a known issue in classification tasks that can lead to predictive bias toward dominant classes. This paper introduces a novel straightforward Bayesian framework that adjusts posterior probabilities to counteract the bias introduced by imbalanced data sets. Instead of relying on the mean posterior distribution of class probabilities, we propose a method that scales the posterior probability of each class according to their representation in the training data.
Active and Passive Offline Breaks Differentially Impact the Consolidation of Procedural Motor Memories in Children and Adults
Authors: Voisin D. , Peigneux P. , Urbain C.
Published: November 2024

Introduction

Short post‐learning breaks, lasting from 5 to 30 min, transiently enhance procedural motor memory performance in adults. However, the impact of activity type (active vs. passive) during the offline break on sequential motor performance remains poorly investigated in children.

Method

This study examined the impact of active versus passive post‐learning breaks on procedural motor memory in 116 healthy participants (58 children, aged 9.03 ± 1.19; 58 adults, aged 22.89 ± 1.77 years). Participants practiced a Finger Tapping Task, reproducing a five‐element keypress sequence as fast and accurately as possible. The task included two sessions (S1 and S2) separated by either a short (30 min) or long (4 h) break. The first 30‐min of the post‐learning break included either a passive (remaining still) or an active (engaging in daily activities) condition.

Results

Repeated‐measures ANOVA revealed significant Session × Age group × Break duration and Session × Break type interaction effects (ps < 0.05). Post hoc analyses indicated Session effects in adults after both Break types, but only after short Break duration (S1 < S2, p < 0.001; long delay p = 0.1). In children, Session effects were observed after both short and long breaks, but only in the active Break type (S1 < S2, ps < 0.001; passive condition p = 0.1).

Conclusion

These results revealed spontaneous post‐learning motor performance improvements at both short and long delays in children, but only in the active post‐training condition, unlike adults who showed improvements only at short delays, regardless of activity type. This suggests developmental differences in offline conditions (duration and activity) linked to plasticity mechanisms underlying procedural motor memory consolidation.
Transcranial Doppler as a Primary Screening Tool for Detecting Right‐to‐Left Shunt in Cryptogenic Stroke Patients?
Authors: Sasannejad Payam , Khosravani Fateme , Ziaei Moghaddam Alireza , Sabi Mohsen Soltani , Jarahi Lida
Published: November 2024

Background

Cryptogenic stroke (CS), a subtype of ischemic stroke with undetermined etiology, accounts for approximately 25% of the cases. Patent foramen ovale (PFO) is an important potential cause of CS via paradoxical embolism. While transesophageal echocardiography (TEE) is the current gold standard for PFO detection, transcranial Doppler (TCD) ultrasound offers a noninvasive alternative with potential advantages in sensitivity for right‐to‐left shunt (RLS) detection. This study's main goal is to evaluate the diagnostic performance of TCD compared to TEE for PFO detection in CS patients.

Methods

We prospectively enrolled 110 patients aged 18–65 years with confirmed CS from 2020 to 2024. All underwent TCD screening for RLS using a standardized protocol. Subsequently, they were categorized based on a simplified version of the Spencer Logarithmic Scale, followed by confirmatory TEE. Clinical characteristics, imaging findings, TCD results, and indications for PFO closure were analyzed.

Results

The mean age of the cohort was 45 years, with 58.2% being males. TEE identified PFO in 44.5% (49/110) of subjects. TCD accurately detected RLS in 42 of the 49 PFO cases (85.7%) confirmed by TEE. For PFO detection, TCD demonstrated a sensitivity of 85.4%, specificity of 88.5%, PPV of 85.4%, and Youden's index of 0.73. Notably, of the seven PFO cases missed by TCD, none received percutaneous closure based on clinical criteria.

Conclusions

TCD exhibited high diagnostic accuracy for detecting high‐risk PFO in patients with CS when compared to the gold‐standard TEE. As a noninvasive modality, TCD may serve as an effective screening tool to identify CS patients who could potentially benefit from confirmatory TEE and subsequent PFO closure intervention. The findings support the use of TCD as a screening tool to triage CS patients for confirmatory TEE and potential PFO closure.
The COVID‐19 Pandemic and Its Influence on Patients With Myotonic Dystrophy Type 1: Lessons Learned
Authors: Kleinveld Vera E. A. , Bruijnes Johanna E. , Labrecque Samuel , Jeurissen‐Bekkering Danielle E. G. , Faber Catharina G. , Horlings Corinne G. C.
Published: November 2024

Introduction: Myotonic dystrophy type 1 (DM1) patients might represent a high‐risk population for severe COVID‐19 disease, as cardiopulmonary symptoms are part of the clinical spectrum of DM1. The COVID‐19 pandemic may have impacted DM1 patients. We aimed to determine the effect of the COVID‐19 pandemic on DM1 patients to guide management strategies in possible future pandemics.

Methods: Data on the presence of a COVID‐19 infection were retrieved from 195 DM1 patients in the MYODRAFT database. Between August 12 and October 4, 2021, 82 patients and proxies filled out a questionnaire on COVID‐19 symptoms, well‐being, and organization of care. Data were compared to prepandemic data.

Results: A total of 18 patients had COVID‐19 (13 confirmed, 5 probable infections). The prevalence of COVID‐19 in our cohort was 9.2%, which was lower than in the Dutch population (11.5%). Four patients (22.2%) were hospitalized due to a COVID‐19 infection, which was higher than in the Dutch population (3.6%). Two infected patients died. A high rate of canceled appointments was reported. Patients reported no change in physical functioning during the pandemic, whereas proxies reported a deterioration in mental and physical well‐being of patients.

Conclusions: The prevalence of COVID‐19 infections was not higher in DM1 patients than in the general population, but DM1 patients are more susceptible to complicated disease when infected. Longitudinal data on patient‐reported physical functioning suggest that the COVID‐19 pandemic and the pandemic management strategies implemented did not influence the course of disease in DM1 patients, and similar strategies can be re‐used in comparable situations.
Cost‐Effectiveness Analysis of Adjuvant Alectinib versus Platinum‐Based Chemotherapy in Resected ALK‐Positive Non‐Small‐Cell Lung Cancer in the Chinese Health Care System
Authors: Wei Qiran , Liang Yifang , Mao Jiahui , Guan Xin
Published: November 2024

Objectives

The ALINE trial demonstrated the superiority of alectinib over platinum‐based chemotherapy in resected Anaplastic Lymphoma Kinase (ALK)‐positive non‐small‐cell lung cancer (NSCLC). Considering the high cost of alectinib, this study aimed to evaluate the economic value of alectinib compared to platinum‐based chemotherapy for treating early‐stage ALK‐positive NSCLC from the perspective of the Chinese health care system.

Materials and Methods

We developed a five‐state Markov model with monthly cycles to estimate the lifetime costs, life‐years (LYs), quality‐adjusted life‐years (QALYs), and incremental cost‐effectiveness ratios (ICERs) in terms of cost per LY gained and per QALY gained. Costs were obtained from database, expert opinions and published literature, and utilities were primarily derived from a multicenter cross‐sectional study based on the Chinese population. Costs and outcomes were discounted at 5% per year. Sensitivity analyses and scenario analyses were conducted to assess uncertainty in model results.

Results

Compared to platinum‐based chemotherapy, alectinib increased total costs by $16,245 and provided gains of 2.02 LYs and 1.84 QALYs over a lifetime horizon. ICERs were $8,052/LY and $8,806/QALY. The ICER in terms of cost per QALY gained was most sensitive to the outcome discount rate. Probabilistic sensitivity analysis indicated a 93% probability of alectinib being cost‐effective at a willing‐to pay (WTP) threshold of $12,367/QALY (1 GDP per capita), rising to 100% at $37,100/QALY (3 GDP per capita).

Conclusion

Alectinib appears to be the preferred cost‐effective option in the adjuvant treatment for Chinese patients with resected early‐stage ALK‐positive NSCLC.
An Insight Review on Phytochemistry, Pharmacological Evidences, and Biosynthesis of Key Metabolites of Indian Himalayan Cherry (Prunus cerasoides Don.) with Emphasis on its Safety and Use in Tradtional Phytomedicine
Authors: Jyotshna  , Shanker Karuna
Published: November 2024

Padmaka (Prunus cerasoides Don.), or wild Himalayan cherry, is a deciduous tree from the Rosaceaae family. The Prunus genus has 400–430 species, including shrubs and trees. It is widely distributed across the Himalayan region of India, China, Myanmar, Nepal, and Thailand. It is used in many classical formulations of various Asian traditional medicinal systems viz., Ayurveda, TCM (traditional Chineese Medicines) and TTM (Traditional Thai Medicines) for treating burning sensations, Blisters, blood disorders, dizziness, bleeding disorders, herps, and skin disorders. The present review covers the research updates on P. cerasoides from 1982 to 2023, accessible on scholars’ platforms and databases. More than 200 phytomolecules have been investigated for their biological potential and the discovery of pharmacophores‐inspired drugs. Padmaka instigated over fifty diverse phytochemicals, viz. flavones, isoflavones, chalcones, terpenoids, glycosides, and sterols. The phytochemical flux of P. cerasoides is dominant with phenylpropanoids, anthocyanins, carotenoids, and terpenoids. Several experimental shreds of evidence emphasized the biological significance of P. cerasoides extracts and their derived phytochemicals. Medicinal significance and its safety in clinical validation have been discussed efficiently. Moreover, the barrier in validated therapeutics is a lack of information on the bioavailability of specialized bioactive, standardization, safety, and toxicokinetic. This review also provides insight into discussions on the key specialized secondary metabolism in P. cerasoides responsible for pharmacological/therapeutic action.
Exploring Fluorinase Substrate Tolerance at C‐2 of SAM
Authors: Lowe Phillip T. , Lüddecke Isabeau , O'Hagan David
Published: November 2024

The fluorinase enzyme (EC 2.5.1.63) utilises fluoride ion and S‐adenosyl‐L‐methionine (SAM) as substrates for conversion to 5′‐fluoro‐5′‐deoxy‐adenosine (5′‐FDA) and L‐methionine (L‐Met). The enzyme has a very strict substrate specificity, however it has been shown to tolerate acetylenes and NH2 replacements for H at C‐2 of the adenine ring of SAM. This substrate tolerance is explored further here with −NHR, −N3, −OR and −SR substituents attached to C‐2. New activities are demonstrated, for example with NH‐methyl, NH‐propyl,NH‐butyl and O‐butyl substrates at C‐2, however azide and thioethers were not tolerated. Outcomes are supported by in silico analysis, revealing favourable H‐bonding interactions involving NH and O substituents at the adenine C‐2 position with N278 and the backbone amide of A279 at the active site respectively. The study informs on the selectivity of the fluorinase as a tool for radiolabelling candidate ligands with fluorine‐18 for positron emission tomography programmes.
Utilizing Invasive Coronary Functional Testing in a Coronary Microvascular and Vasomotor Dysfunction Program: Methods and Considerations
Authors: Quesada Odayme , Ashokprabhu Namrita D. , Tapp Danielle N. , Hamstra Michelle S. , Losekamp Melissa , Schmidt Christian , Palmer Cassady , Gallatin Julie , Tierney Darlene , Trenaman Tammy , Canoniero Mariana , Frizzell Jarrod , Henry Timothy D.
Published: November 2024

Background

Coronary microvascular and vasomotor dysfunction (CMVD) is associated with a threefold increased risk of major adverse cardiovascular events (MACE) and is the primary mechanism responsible for angina/ischemia in patients with nonobstructive coronary artery disease (ANOCA/INOCA). Proper assessment for CMVD is vital to provide targeted treatment and improve patient outcomes. Invasive coronary functional testing (ICFT) is the “gold standard,” for CMVD assessment and can be used to diagnose all endotypes. However, there is a lack of standardization for ICFT protocols and use in the treatment of CMVD.

Aims

To provide a comprehensive overview of ICFT protocols utilized at the Christ Hospital Womens Heart Center (TCH‐WHC).

Methods

Here, we outline our standard operating procedures for ICFT utilized at TCH‐WHC, including the procedures two main methods: Doppler and Thermodilution. We describe our structured approach for ICFT referral and postdiagnostic clinical management utilized at The Christ Hospital Women's Heart Center (TCH‐WHC) CMVD program. We then quantified how ICFT has contributed to growth of the TCH‐WHC.

Results

From October of 2020 until July of 2024, a total of 422 patients have undergone ICFT at TCH‐WCH, 64% were performed via the Doppler protocol and 36% were performed via the Thermodilution protocol. Based on exclusive endotype categories, 19% had an endothelial‐independent CMD alone, 19% had endothelial‐dependent CMD or microvascular VSA alone, 3% had epicardial VSA alone, 42% had mixed disease (any combination of the above categories), and 17% had a normal ICFT.

Conclusions

ICFT provides opportunity to provide diagnostic clarity and optimize medical treatment for CMVD. TCH‐WHC's structured approach for ICFT referral and protocol for conducting comprehensive ICFT which has been vital for the growth of our specialized CMVD program.
The impact of mechanical scouring and moisture conditioning on the in vitro protein digestibility and quality of roller‑milled green lentil (Lens culinaris) and yellow pea (Pisum sativum)
Authors: Franczyk Adam J. , Bui Nguyen , Chen Jiayi , Boyd Lindsey , Wang Ning , Sopiwnyk Elaine , Sarkar Ashok , Neufeld Jason , Paliwal Jitendra , Nickerson Michael , House James D.
Published: November 2024

Background and Objectives

Milling practices, otherwise refined for specific uses in cereal‐based foods, have not been thoroughly developed for pulses. This study investigates whether scouring and moisture conditioning pretreatments on yellow peas and green lentils can enhance hull removal, and in turn, whether changes in hull removal alter in vitro protein digestibility and quality.

Findings

Total by‐product losses were significant in green lentils when subject to scouring, which was altered by high moisture addition in yellow peas. The scouring pretreatment altered both the protein digestibility and amino acid scores of green lentils, which translated to improved protein quality in all streams, but significantly in the break flour stream. Yellow peas similarly demonstrated significant improvements in protein quality from scouring, as a result of altered amino acid scores.

Conclusion

The addition of a scouring procedure can improve the protein quality of yellow peas and green lentils.

Significance and Novelty

Pulse milling procedures are rarely evaluated for optimization of protein quality. This research establishes milling protocols that may be used to enhance the protein quality of yellow peas and green lentils.
Fanconi Anemia: Challenges in Diagnosis and Management—A Case Series Report
Authors: Eghbali Aziz , Safdari Seyed Mehrab , Yousefi Roozbahani Maedeh , Tavajohi Khatereh , Hosseini Soudabeh
Published: November 2024

Fanconi anemia (FA) is a rare inherited disorder characterized by congenital abnormalities, progressive bone marrow failure, and a predisposition to malignancies. Detecting FA can be challenging, as it involves identifying increased chromosomal sensitivity to DNA cross‐linking agents and detecting causative genetic variants via genome sequencing. We report two cases of siblings with FA, both confirmed to have the FANCD2 variant through whole‐exome sequencing (WES). The first patient presented with epistaxis, petechiae, ecchymosis, and lower limb edema. The second patient exhibited epistaxis, diabetes, developmental delay, and physical abnormalities. Interestingly, both patients had negative results on the initial chromosomal breakage test with mitomycin C, a commonly used diagnostic tool for FA. However, further investigation with WES revealed the presence of the FANCD2 variant, confirming the FA diagnosis. This case report highlights the challenges in diagnosing FA, particularly when initial screening tests yield negative results. Molecular genetic testing, such as WES, can provide a definitive diagnosis and guide appropriate management strategies. Early and accurate diagnosis is crucial for improving outcomes in individuals with this potentially fatal illness, as promising advancements in treatments such as hematopoietic stem cell transplantation and gene therapy offer hope for addressing FA.
CoFe Hydroxide Nanospheres for Enhanced Alkaline Water Splitting and Seawater Oxidation:Anion Doping Effects of Fluorine and Carbonate
Authors: Zheng Tingting , Shi JunYu , Wang Dandan , Min Yulin , Xu Qunjie , Li Qiaoxia
Published: November 2024

Green hydrogen production can be achieved through electrolysis of fresh water or the use of renewable energy to electrolyze seawater. However, due to the low activity and poor stability of oxygen evolution reaction catalysts, direct electrolysis of alkaline seawater faces significant challenges. Herein, The catalyst F‐CoFe(OH)‐CO3/NF with three‐dimensional nanosphere structure was prepared, The introduction of CO32− into the intermediate layer of CoFe hydroxide improves the corrosion resistance of alkaline electrolyte and the doping of F− is to design three‐dimensional layered nanostructures, increase the active site, and accelerate the diffusion of the electrolyte. By in situ Raman analysis, partial oxidation of CoFe hydroxide to CoFe (oxy)hydroxide as the active center can accelerating the adsorption of oxygen‐related intermediates. In 1 M KOH, it requires overpotentials of 210 mV and 251 mV to drive current densities of 10 and 100 mA cm−2, respectively. And it remained stable at the current density of 100 mA cm−2 for 120 h in 1 M KOH. F‐CoFe(OH)‐CO3/NF can also catalyzes the decomposition of electrolytic seawater. Compared with hydroxide, anion‐doped carbonate hydroxide is more efficient and stable in electrolyte solution, which is of great importance for the development of a new stable electrocatalyst for water decomposition.
Stereological Analysis of the Rhesus Monkey Perirhinal and Parahippocampal Cortices
Authors: Villard Justine , Chareyron Loïc J. , Banta Lavenex Pamela , Amaral David G. , Lavenex Pierre
Published: November 2024

The perirhinal and parahippocampal cortices are key components of the medial temporal lobe memory system. Despite their essential roles in mnemonic and perceptual functions, there is limited quantitative information regarding their structural characteristics. Here, we implemented design‐based stereological techniques to provide estimates of neuron number, neuronal soma size, and volume of the different layers and subdivisions of the perirhinal and parahippocampal cortices in adult macaque monkeys (Macaca mulatta, 5–9 years of age). We found that areas 36r and 36c of the perirhinal cortex and areas TF and TH of the parahippocampal cortex exhibit relatively large superficial layers, which are characteristic of the laminar organization of higher order associational cortices. In contrast, area 35 of the perirhinal cortex exhibits relatively large deep layers. Although neuronal soma size varies between subdivisions and layers, neurons are generally larger in the perirhinal cortex than in the parahippocampal cortex and even larger in the entorhinal cortex. These morphological characteristics are consistent with the hierarchical organization of these cortices within the medial temporal lobe. Comparing data in rats, monkeys, and humans, we found species differences in the relative size of these structures, showing that the perirhinal and parahippocampal cortices have expanded in parallel to the cerebral cortex and may play a greater role in the integration of information in the neocortical–hippocampal loop in primates. Altogether, these normative data provide an essential reference to extrapolate findings from experimental studies in animals and create realistic models of the medial temporal lobe memory system.
Presence and Impact of Adverse Childhood Experiences and Reflective Functioning on Aggression in Adults With Antisocial Behaviour
Authors: Luijkx Judith , van Loon Linda M. A. , De Wit‐De Visser Brenda , van Dam Arno
Published: November 2024

This cross‐sectional study investigated the relationship between the presence and impact of ACEs with both reactive and proactive aggression, and the possible moderating role of mentalization (operationalized as reflective functioning) in these expected relationships. Sixty‐five inpatient and outpatient adults with any kind of antisocial behaviour completed the Dutch version of the Traumatic Experiences Checklist, the Reactive‐Proactive Aggression Questionnaire, and the Adult Attachment Interview with the use of the Reflective Functioning Scale. Preliminary analysis showed a remarkably high level of ACEs, and a relatively high reported impact of these experiences. We found a positive relationship between the total presence of ACEs (including childhood maltreatment and adverse household factors), and both reactive and proactive aggression. We also found positive relationships between the experienced impact of these ACEs and both reactive and proactive aggression. Regarding childhood maltreatment in family of origin, we did not find a correlation between the presence of these experiences and respectively reactive and proactive aggression. However, we found a correlation between the impact of childhood maltreatment and reactive aggression. These results suggest that in addition to the cumulative experience of ACEs, the subjective burden of these experiences on individuals must not be underestimated in case of aggression. Additional moderation analysis showed no differences in these relationships in case of less developed versus medium‐high developed reflective functioning. The findings substantiate the importance of early prevention and treatment programs with focus on ACEs to possibly reduce aggression.