bluuebunny/crossref_metadata_2025 huggingface dataset:
Rational Design and Engineering of Terminal Functional Groups in Dibenzothiophene‐Diphenylamine Small Molecular Electron Donors for Enhanced Photovoltaic Efficiency in All‐Small‐Molecule Organic Solar Cells
Authors: Akram Waqas , Walayat Amber , Zahid Waqar Ali , Khan Gul Shahzada , Alanazi Meznah M. , Elmushyakhi Abraham , Iqbal Javed
Published: June 2024

All‐small‐molecule organic solar cells (ASM‐OSCs) offer advantages like well‐defined molecular structures and excellent reproducibility. However, lower photovoltaic efficiencies hinder their adoption due to limitations in designing small molecular electron donors (SMEDs) with optimal energy levels, light absorption, and optoelectronic properties. The present study addresses this gap by rationally designing a series of SMEDs (DBT‐2FA1 to DBT‐2FA6) through terminal acceptors engineering into dibenzothiophene core with diphenylamine side donors for potential applications in ASM‐OSCs. Density functional theory simulations are carried‐out to establish structure‐property relationships based on structural, electrochemical, photophysical, and charge transfer (CT) properties. Results show that the SMEDs exhibit low‐lying HOMOs for suitable energy level alignment with benchmark Y6 acceptor, promoting open‐circuit voltage and charge separation. The panchromatic absorption spectra covering Vis‐NIR region and maximum light harvesting efficiency are beneficial for high current‐density in ASM‐OSCs. Notably, the push‐pull mechanism within SMEDs results in dominant intramolecular CT with above 70% CT excitations. Whereas, a moderate variation in dipole moments and electrostatic potential differences with acceptor material led to 99.9% intermolecular CT, thus ensuring robust exciton dissociation and efficient photocurrent generation. Overall, this work provides a molecular‐level understanding of designing novel SMEDs and their compatibility with acceptor materials for developing future high‐performance ASM‐OSCs.
Addressing Heterogeneity in Direct Analysis of Extracellular Vesicles and Their Analogs by Membrane Sensing Peptides as Pan‐Vesicular Affinity Probes
Authors: Gori Alessandro , Frigerio Roberto , Gagni Paola , Burrello Jacopo , Panella Stefano , Raimondi Andrea , Bergamaschi Greta , Lodigiani Giulia , Romano Miriam , Zendrini Andrea , Radeghieri Annalisa , Barile Lucio , Cretich Marina
Published: June 2024

Extracellular vesicles (EVs), crucial mediators of cell‐to‐cell communication, hold significant diagnostic potential due to their ability to concentrate protein biomarkers in bodily fluids. However, challenges in isolating EVs from biological specimens hinder their widespread use. The preferred strategy involves direct analysis, integrating isolation and analysis solutions, with immunoaffinity methods currently dominating. Yet, the heterogeneous nature of EVs poses challenges, as proposed markers may not be as universally present as thought, raising concerns about biomarker screening reliability. This issue extends to EV‐mimics, where conventional methods may lack applicability. Addressing these challenges, the study reports on Membrane Sensing Peptides (MSP) as pan‐vesicular affinity ligands for both EVs and their non‐canonical analogs, streamlining capture and phenotyping through Single Molecule Array (SiMoA). MSP ligands enable direct analysis of circulating EVs, eliminating the need for prior isolation. Demonstrating clinical translation, MSP technology detects an EV‐associated epitope signature in serum and plasma, distinguishing myocardial infarction from stable angina. Additionally, MSP allow analysis of tetraspanin‐lacking Red Blood Cell‐derived EVs, overcoming limitations associated with antibody‐based methods. Overall, the work underlines the value of MSP as complementary tools to antibodies, advancing EV analysis for clinical diagnostics and beyond, and marking the first‐ever peptide‐based application in SiMoA technology.
Leveraging unsupervised machine learning to examine women's vulnerability to climate change
Authors: Caruso German , Mueller Valerie , Villacis Alexis
Published: June 2024

We provide an application of machine learning to identify the distributional consequences of climate change in Malawi. We compare climate impact estimates based on drought indicators established objectively from the k‐means algorithm to more traditional measures. Young women affected by drought were 5 percentage points more likely to be married by 18 than those living in nondrought areas. Our approach generates robust results when varying the number of clusters and definition of treatment status. In some cases, we find the design using k‐means to define treatment is more likely to satisfy the assumptions underlying the difference‐in‐differences strategy than when using arbitrary thresholds. Projections from the estimates indicate future drought risk may lead to larger declines in labor productivity due to women's engagement in early age marriage than other factors affecting their participation rates. Under the extreme representative concentration pathway scenario, drought exposure encourages the exit of 3.3 million women workers by 2100.
NANS‐CDG: Expanding clinical insights with a novel patient with novel variants
Authors: Yoo Sukdong , Cheon Chong Kun
Published: June 2024

N‐acetyl‐d‐neuraminic acid synthase‐congenital disorder of glycosylation (NANS‐CDG) is a rare autosomal recessive defect in the N‐acetyl‐neuraminic acid biosynthesis pathway. Herein, we report the first Korean NANS‐CDG patient. A 10‐year‐old boy was referred to our clinic because of incidental radiographic findings indicating spondyloepimetaphyseal dysplasia. The patient had microcephaly, cavum septum pellucidum, and ventriculomegaly at birth, and at 10 years, a very short stature. He had a history of idiopathic chronic immune thrombocytopenia, central adrenal insufficiency, and hypothyroidism since infancy. The first unprovoked seizure occurred at the age of 2 years, and he was subsequently admitted to the hospital frequently because of respiratory infections and intractable seizures. Exome sequencing identified unreported biallelic variants of the NANS gene. Clinical and genetic confirmation of NANS‐CDG highlights its expanding phenotypic and genotypic diversity.
Expanded phenotype and cancer risk in patients with Beckwith–Wiedemann spectrum caused by CDKN1C variants
Authors: George Andrew M. , Viswanathan Aravind , Best Lyle G. , Monahan Caitlin , Limmina Maria , Ganguly Arupa , Kalish Jennifer M.
Published: June 2024

Beckwith–Wiedemann spectrum (BWSp) is caused by genetic and epigenetic alterations on chromosome 11 that regulate cell growth and division. Considering the diverse phenotypic landscape in BWSp, the characterization of the CDKN1C molecular subtype remains relatively limited. Here, we investigate the role of CDKN1C in the broader BWSp phenotype. Notably, patients with CDKN1C variants appear to exhibit a different tumor risk than other BWSp molecular subtypes. We performed a comprehensive literature review using the search term “CDKN1C Beckwith” to identify 113 cases of patients with molecularly confirmed CDKN1C‐BWSp. We then assessed the genotype and phenotype in a novel cohort of patients with CDKN1C‐BWSp enrolled in the BWS Research Registry. Cardinal and suggestive features were evaluated for all patients reported, and tumor risk was established based on available reports. The most common phenotypes included macroglossia, omphalocele, and ear creases/pits. Tumor types reported from the literature included neuroblastoma, acute lymphocytic leukemia, superficial spreading melanoma, and intratubular germ cell neoplasia. Overall, this study identifies unique features associated with CDKN1C variants in BWSp, enabling more accurate clinical management. The absence of Wilms tumor and hepatoblastoma suggests that screening for these tumors may not be necessary, while the neuroblastoma risk warrants appropriate screening recommendations.
Siblings with vitamin D‐dependent rickets type 1A: Importance of genetic testing and a review of genotype–phenotype correlations
Authors: Wang Leonard Kuan‐Pei , Shanmugasundaram Manjushree , Cooney Erin , Lee Phillip D. K.
Published: June 2024

Vitamin D‐dependent rickets type 1A (VDDR1A) is a rare condition caused by biallelic pathogenic variants in CYP27B1, which encodes 25‐hydroxyvitamin D3‐1‐α‐hydroxylase. Inadequate activity of this enzyme results in deficient 1α‐hydroxylation of inactive 25‐hydroxyvitamin D to biologically active 1,25‐dihydroxyvitamin D, with consequent adverse effects on calcium and phosphate metabolism. A female child was clinically diagnosed at 18 months old with hypophosphatemic rickets based on phenotype and biochemical testing, with neither parent affected. A subsequent affected male sibling led to the reconsideration of the diagnosis. Exome sequencing showed a homozygous CYP27B1 c.1040T>A (p.Ile347Asn) variant for both children. No variants were found in genes associated with hypophosphatemic rickets. A review of published cases of VDDR1A with homozygous CYP27B1 variants indicates variable clinical presentation, lack of genotype–phenotype correlation, and low serum phosphate at diagnosis in most cases. These findings emphasize the clinical importance of molecular testing as part of the diagnostic evaluation for cases of non‐nutritional rickets.
Ethical futures in biological anthropology: Research, teaching, community engagement, and curation involving deceased individuals
Authors: de la Cova Carlina , Hofman Courtney A. , Marklein Kathryn E. , Sholts Sabrina B. , Watkins Rachel , Magrogan Paige , Zuckerman Molly Kathleen
Published: June 2024

Although ethical reforms in biological anthropology have gained ground in recent years, there is still a scarcity of ethical standards for work involving historical documented collections (HDCs) at US museums and universities. These collections of deceased individuals were created in the late 19th to mid‐20th centuries under anatomy laws that targeted socially marginalized communities and allowed for the dissection of these individuals without their consent. Due to the extensive information associated with the individuals and made available to researchers, these collections have served as foundational resources for theory and methods development in biological anthropology into the 21st century. Recognizing the need for ethical guidelines for research, teaching and training, community engagement, and curation involving HDCs, we held a workshop called “Ethical Futures for Curation, Research, and Teaching in Biological Anthropology” on November 15–17, 2021. Here we summarize the conversations and major points of consensus among the workshop participants on these topics in order to advance these ethical considerations more broadly across the field.
The family emotional system
Authors: Papero Daniel V.
Published: June 2024

The family emotional system (FES) regulates the functioning of the human family. As described by Bowen, the FES contains several components. Two forces, the togetherness and individuality forces, function in proportional opposition to one another. Anxiety, the emotional response of the organism to real or imagined threat, provides the motivational energy that powers the system. Two equilibria lie at the centre of the family emotional system, emotional equilibrium and functional equilibrium. When the two are in balance, a condition Bowen called emotional harmony prevails. A third equilibrium, the togetherness–individuality equilibrium, regulates the lability of emotional harmony. Disturbances of emotional harmony result in the activation of automatic mechanisms and processes that support the restoration of emotional harmony. Like the mechanisms that support homeostasis in the living organism, they work optimally when rapidly engaged and quickly disengaged when balance is restored. Prolonged disturbance of emotional harmony results in a resetting of the togetherness–individuality equilibrium in favour of increased togetherness, establishing a new, more sensitive set point around which the FES now stabilises. To maintain the new more labile condition, one or more of the mechanisms becomes chronically engaged, indicating an emotional adaptation of the system and a potential for the development of a symptom as a consequence of the adaptation. Finally, the work on differentiation of self (One of eight concepts that comprise the formal Bowen theory, the scale of differentiation of self places human functioning on a single continuum based upon ‘… the degree to which people are able to distinguish between the feeling process and the intellectual process (Bowen, 1978, p. 355)’. The degree of differentiation, according to Bowen, affects how people manage themselves in personal relationships and in their efforts to adapt to the challenges of life (Bowen, 1978). The work on differentiation, an aspect of family psychotherapy, describes the effort people make to become better observers of themselves in relationships and in the processes of problem‐solving related to challenge. It involves the effort the person makes to manage emotional reactiveness, an instinctive, reflexive response to stimuli encountered, to guide behavior thoughtfully, and to enhance emotional autonomy within the network or system of family relationships.) can lead to a progressive reset of the balance from less to more stable, representing an enhancement of adaptive competency.
A ratiometric and selective fluorescent nanosensor for determining Hg2+ ions based on a novel functionalized metal–organic framework
Authors: Khalil Muhammad A. , El‐marghany Adel , Kubra Khadiza Tul , Shahat Ahmed
Published: June 2024

A new method using fluorescence was developed to detect Hg2+ ions in water. This method relied on the reaction between NH2‐MIL‐53(Al) and 5‐bromo‐2‐hydroxyacetophenone. The method was carefully fine‐tuned for optimal reaction conditions and analytical parameters like pH levels, nanosensor quantity, and detection limits. It showed great linearity in detecting Hg2+ ions in the range of 0.0–3.0 ppm (0.0–1.50 × 10−5 M), with a very low detection limit of 1.65 × 10−2 ppm (8.23 × 10−8 M). We tested how well the method can distinguish between different substances by investigating whether other common substances in water samples would interfere. The results were positive, as the presence of these substances did not significantly affect the accuracy of detecting Hg2+ ions, confirming the method's reliability. In order to confirm its dependability, we conducted a quantitative test to detect Hg2+ ions in water samples. The recovery rates obtained ranged from 97.16% to 103.2%, demonstrating the method's precision and accuracy. A comparison with inductively coupled plasma optical emission spectrometry (ICP‐OES), a well‐known method for analyzing trace metals, produced similar results, further instilling confidence in the 5Br2HA = N‐Al‐MOF nanosensor that was developed. In general, this research emphasizes the exciting potential of the new nanosensor in detecting Hg2+ ions in various water and cosmetic samples. It provides a strong and dependable alternative to traditional detection methods.
Synthesis, structural characterization, density functional theory, anticancer, and antimicrobic studies of Ni2+ and Cu2+ complexes encompassing tridentate ONS‐donor azo‐thiosemicarbazone
Authors: Hassan Essam A. , Ebrahium Mohamad M. , Al‐Hakimi Ahmed N.
Published: June 2024

This study focuses on the synthesis of azo‐thiosemicarbazone ligand, which is designed by reacting 2‐hydroxy‐5‐(phenyldiazenyl)benzaldehyde with hydrazine carbothioamide. Hence, this ligand was exploited for chelation with nickel and cupric salts in (1 M:1 L) molar ratio. These synthetics were structurally investigated using a variety of physical, analytical, and spectroscopic (1D/2D‐NMR, UV–Vis, FT‐IR, and E‐mass) tools as well as theoretically. The finding demonstrated that the resulting azo‐thiosemicarbazone (H4Azo‐TSC) bonded with the nickel and cupric ions as mono/di‐basic tridentate chelators, binding them via deprotonated phenolic oxygen, imino nitrogen, and thionic/thiol sulfur atoms adopting square planar geometry. The theoretical investigation was examined by DFT/B3LYP/LanL2dZ, including energetic parameters, HOMO‐LUMO energy gap, dipole moment, and geometrical optimization, which were applied to support the complexes' geometrical structure. The in vitro microbicidal activities of the azo‐thiosemicarbazone, compared with its Ni2+ and Cu2+ complexes, display superior activity over the metal complexes against different bacterial and fungal species. The anticancer efficacy of the synthetics was tested against human lung fibroblast (WI38) and mammary gland breast cancer (MCF‐7) compared with Doxorubicin as a standard drug. The cytotoxic efficiency of metallic complexes exceeded that of un‐chelated azo‐thiosemicarbazone. The most effective complex is Ni2+ complex with IC50 equal to 11.75 and 14.05 μg/ml, respectively. It has been demonstrated that Ni2+ and Cu2+ complexes are more biocompatible than free azo‐thiosemicarbazone; this finding may be related to the chelation process.
The effects of the contents of modified‐diatomite on the properties of modified‐diatomite/epoxy resin composites
Authors: Wang Huixiao , Lou Chunhua , Yu Jingjing , Yang Yuxin
Published: June 2024

External plasticization is one of the effective ways to toughen epoxy resins. In this study, an inorganic filler (EMD) was prepared by chemical modification of diatomite and was used to fill epoxy resin matrix. The effects of different amounts (5%, 10%, 15%, and 20%) of raw diatomite (RD) and modified‐diatomite (EMD) on the mechanical and thermal properties of epoxy resin composites were studied. The mechanical results showed that the impact strength, tensile strength, and bending strength of EMD/EP were higher than those of RD/EP. The impact strength of EMD‐15/EP reached 5.39 KJ/m2, which was 36.8% higher than that of RD‐15/EP. Thermogravimetric analysis showed that the thermal stability of EMD/EP was better than that of RD/EP. The results of DMA show that the glass transition temperature of EMD/EP was lower than that of RD/EP. Non‐isothermal differential scanning calorimetry study showed that the apparent activation energy of EMD‐15/EP was much lower than that of RD‐15/EP, which proved that EMD could promote the curing of epoxy resin. The Malek method was used to determine that both the RD‐15/EP and EMD‐15/EP curing systems were autocatalytic (Šesták–Berggren) models.
Carbonated castor oil as a bioplasticiser and toughening agent for bisphenol a based epoxy
Authors: Dhore Nikhil , Kottaron Amaya Othayoth , Palanisamy Aruna , Narayan Ramanuj
Published: June 2024

Diglycidyl ether of bisphenol A (DGEBA), a key intermediate for epoxy resins, provides strong adhesion, processability and the resulting thermoset boasts high cross linking density. However, the inherent brittleness and susceptibility to cracking restrict its advanced applications. To overcome these drawbacks, CO2 fixed cyclic carbonate from castor oil (CCO) was synthesized from epoxidised castor oil (ECO) and used in varying quantities as a toughening agent for amine cured DGEBA. Different amines have been utilized to cure the epoxy and to study the structure–property relationship by fixing the amount of CCO. The inclusion of 10% CCO resulted in improvement in the tensile strength, storage modulus, flexural modulus, and impact strength of the epoxy‐urethane hybrid. Moreover, the epoxy‐urethane networks had reduced cross linking density imparted by the fatty acid units of CCO and the presence of unreacted carbonate groups facilitated molecular movement, thereby contributing to energy dissipation during the deformation process. Further incorporation of the CCO lowers the mechanical properties of the hybrids due to a reduction in cross linking density. Trimethylolpropane tris[poly(propyleneglycol)amine terminated] ether cured system exhibited the highest thermal stability compared to hexamethylene diamine, isophorone diamine, and 4,7,10‐trioxa‐1,13 tridecanediamine. The Tg decreased as the CCO content increased, while the water contact angle increased.
Recent advances on quinoxalines as target‐oriented chemotherapeutic anticancer agents through apoptosis
Authors: Nafie Mohamed S. , Kahwash Shaima H. , Youssef Magdy M. , Dawood Kamal M.
Published: June 2024

The current review outlines all possible recent synthetic platforms to quinoxaline derivatives and the potent stimulated apoptosis mechanisms targeted by anticancer therapies. The currently reported results disclosed that quinoxaline derivatives had promising anticancer potencies against a wide array of cancer cell lines, better than the reference drugs, through target inhibition. This review summarizes some potent quinoxaline derivatives with their synthesis strategies and their potential activities against various molecular targets. Quinoxalines can be considered an important scaffold for apoptosis inducers in cancer cells through inhibiting some molecular targets, so they can be further developed as target‐oriented chemotherapeutics.
Multiparametric‐magnetic resonance imaging (mp‐MRI) of the prostate and Urolift: Identifying artefact size, location and clinical implications
Authors: Parkin Cameron James , Jyoti Rajeev , Chin Peter
Published: June 2024

Objectives

We sought to define the degree of artefact caused by prostatic urethral lift (PUL) on multiparametric‐magnetic resonance imaging (mp‐MRI) to determine the location, size of artefact and if the device could potentially obscure a diagnosis of prostate cancer.

Methods

Ten patients were prospectively enrolled to undergo PUL for treatment of benign prostatic hyperplasia and follow‐up imaging. A standard mp‐MRI protocol using a 3.0 Tesla scanner was performed prior to and following Urolift insertion. Pre‐ and post‐PUL images were compared to measure maximum artefact diameter around each implant in each MRI parameter. A transverse relaxation time weighted (T2) artefact reduction protocol was also evaluated. The location of each artefact was then compared to a separate database of 225 consecutive patients who underwent magnetic resonance guided prostate biopsies.

Results

Artefact occurred around the stainless steel urethral implant component only. Mean T2 artefact maximum diameter was 7.7 mm (sd = 1.71 mm), with an artefact reduction protocol reducing this to 5.4 mm (sd = 1.43). Mean dynamic‐contrast‐enhancement artefact was 10 mm (sd = 2.5 mm), and mean diffusion‐weighted‐imaging artefact was 28.2 mm (sd = 7.8 mm). All artefacts were confined to the posterior transition zone only. In the 225 consecutive patients who had undergone magnetic resonance guided prostate biopsies, there were 55 positive biopsies with prostate cancer, with 13 cases found in the transition zones and no cancer identified solely in the posterior transitional zone.

Conclusions

The stainless steel urethral component of the PUL does cause artefact, which is confined to the posterior transition zone only. PUL artefact occurs in an area of the prostate that has a very low incidence of a single focus of prostate cancer. If there is concern for prostate cancer in the posterior TZ (e.g. if every other area is clear with a high PSA), this area can undergo targeted biopsy.
Rodent anogenital distance recommendations
Authors: Wise L. David
Published: June 2024

Background

Measurement of rat anogenital distance (AGD) dates to at least 1912. Increased interest in endocrine disrupting chemicals and the use of AGD as a biomarker for fetal androgen effects have increased the number of studies with this endpoint in recent decades. A literature review revealed different landmarks, methods of measurement, and methods to adjust for body weight differences. AGD is often reported to hundredths of millimeters and as such, deserves precision in all these aspects. This paper presents recommendations for the measurement and analysis of rodent AGD.

Methods

Literature and regulatory guidance documents that mentioned or measured rodent AGD were reviewed. Four adjustment methods were evaluated using available online data from three rat studies each with two generations of offspring.

Results

Tabulation of studies reveals that species/stocks and time of data collection, but more importantly anatomical landmarks and methods of measurement have produced a variety of results which are difficult to compare. Not all studies have adjusted for test article effects on body weight (and thus size). The four adjustment methods were fairly comparable.

Conclusion

Recommendations are as follows. A microscopic method should be used to measure AGD of late rodent fetuses and early postnatal pups. The caudal edge of the genital tubercle and the cranial edge of the anus are clear and identifiable landmarks. The simplest adjustment is to divide individual AGDs by the cube root of animals’ body weight. These recommendations will help ensure data consistency and accuracy, and facilitate meaningful comparisons across laboratories and chemical classes.
Effectiveness of educational interventions: An ecological systems analysis of initiatives from the UK opportunity areas programme
Authors: Spear Sara , Kirkman Phil
Published: June 2024

Government interventions to address inequalities in education are common in the United Kingdom and internationally. Whilst there is a tendency for policy discourse to focus on benchmarks and indicators as measures of educational success, the inclusiveness and effectiveness of government interventions in education has been questioned. This paper uses the ecological systems perspective as a way of analysing how government interventions may, or may not, lead to real impact on young people's educational outcomes. Two case studies are presented on projects funded as part of the opportunity areas (OA) programme in England to tackle barriers to learning for young people: Ipswich ‘Learning Behaviour Leads’ and Norwich ‘Engagement Coaches’. The research team carried out an evaluation of these projects in seven schools, using a mixed methods approach which involved interviews and reflective journals by the staff delivering the projects (n = 7), interviews with members of the school senior leadership teams (n = 7), an online survey with teachers (n = 23) and focus groups with young people involved in the projects (n = 14). The evaluation found that although there was shared understanding of the purpose and priorities of the OA programme between the macro and exosystems, there were tensions between these and the microsystem, and a lack of interconnection with the mesosystem. Whilst the projects benefited the young people involved, they fell short of the initial intentions to foster engagement amongst the most at‐risk groups, and failed to address the macro aims of fostering a pan‐system response.
Development of growth selection system and pocket engineering of d‐amino acid oxidase to enhance selective deamination activity toward d‐phosphinothricin
Authors: Cheng Feng , Sun Ke‐Xiang , Gong Xiao‐Xiao , Peng Wei , Zhang Hua‐Yue , Liang Xi‐Hang , Xue Ya‐Ping , Zheng Yu‐Guo
Published: June 2024

D‐amino acid oxidase (DAAO)‐catalyzed selective oxidative deamination is a very promising process for synthesizing l‐amino acids including l‐phosphinothricin (l‐PPT, a high‐efficiency and broad‐spectrum herbicide). However, the wild‐type DAAO's low activity toward unnatural substrates like d‐phosphinothricin (d‐PPT) hampers its application. Herein, a DAAO from Caenorhabditis elegans (CeDAAO) was screened and engineered to improve the catalytic potential on d‐PPT. First, we designed a novel growth selection system, taking into account the intricate relationship between the growth of Escherichia coli (E. coli) and the catalytic mechanism of DAAO. The developed system was used for high‐throughput screening of gene libraries, resulting in the discovery of a variant (M6) with significantly increased catalytic activity against d‐PPT. The variant displays different catalytic properties on substrates with varying hydrophobicity and hydrophilicity. Analysis using Alphafold2 modeling and molecular dynamic simulations showed that the reason for the enhanced activity was the substrate‐binding pocket with enlarged size and suitable charge distribution. Further QM/MM calculations revealed that the crucial factor for enhancing activity lies in reducing the initial energy barrier of the reductive half reaction. Finally, a comprehensive binding‐model index to predict the enhanced activity of DAAO toward d‐PPT, and an enzymatic deracemization approach was developed, enabling the efficient synthesis of l‐PPT with remarkable efficiency.
Atrial septal interventions during and after hybrid stage I palliation of hypoplastic left heart syndrome
Authors: Thomas Courtney , Sower Christopher Todd , Romano Jennifer C. , Balasubramanian Sowmya , Yu Sunkyung , Lowery Ray , Zampi Jeffrey D.
Published: June 2024

Background

Hybrid stage I palliation (HS1P) is an alternative approach for initial palliation in hypoplastic left heart syndrome (HLHS) patients. Unlike surgical stage I palliation where atrial septectomy is routinely performed, atrial septal intervention (ASI) during HS1P is variable. In this study, we described our experience with ASI in single ventricle (SV) patients who underwent HS1P and identified factors associated with need for ASI after HS1P.

Methods

Data were retrospectively collected for all HLHS patients who underwent HS1P at our center over the past 12 years. We evaluated ASIs performed during the HS1P (intra‐HS1P ASI) and ASIs performed during the period from HS1P to the subsequent surgical stage, either interval Norwood stage I or comprehensive stage II (post‐HS1P ASI). Patient factors and procedural data were compared to identify factors associated with undergoing post‐HS1P ASI and the impact of ASI on patient outcomes was evaluated.

Results

Of 50 SV patients included, 23 (46%) underwent intra‐HS1P ASI and 26 (52%) underwent post‐HS1P ASI. Need for post‐HS1P ASI was lower among patients who had an intra‐HS1P ASI as compared to those who did not (30% vs. 70%; p = 0.005). There were no significant differences in short or Midterm outcomes between patients who underwent intra‐HS1P ASI or post‐HS1P ASI and their counterparts.

Conclusions

ASI is common both during and after HS1P but is generally well tolerated and type of ASI does not significantly impact overall patient outcomes. Our findings suggest that the current approach of individualizing management of ASI in the HS1P population is effective and safe.
Cerebral venous sinus thrombosis in patient of immune thrombocytopenic purpura managed with mechanical thrombectomy: An anecdotal endovascular experience from lower middle income country
Authors: Ghimire Sagun , Shrestha Shikher , Shrestha Dinuj , Ranabhat Kajan , Bhattarai Suman , Maharjan Ananta , Jaiswal Bibek , Chaudhary Prabin
Published: June 2024

Key Clinical Message

Cerebral venous sinus thrombosis in itself is rarely encountered clinical entity and its association with immune thrombocytopenic purpura (ITP) makes it more unusual presentation. No any as such standard guidelines exist that guides the prompt evidence based management in such concurrent cases but neuroendovascular modality can play a pivotal role.
Transorbital penetrating intracranial injury involving bilateral frontal lobes with evisceration of right eye: A case report
Authors: Siddiqui Abdul Rehman , Kariem Kaiser , Fayaz Mohsin , Scalia Gianluca , Chaurasia Bipin
Published: June 2024

Key Clinical Message

Timely diagnosis, multidisciplinary surgical intervention, and appropriate imaging are crucial in managing transorbital‐penetrating intracranial injuries (TOPIs), minimizing morbidity, and optimizing patient outcomes.

Transorbital‐penetrating intracranial injuries (TOPIs) are rare occurrences with potential for severe neurological complications and high mortality rates. Prompt diagnosis and management are essential to mitigate adverse outcomes. Understanding injury patterns and employing appropriate imaging modalities are crucial for effective surgical planning and patient care. We present a case of a 22‐year‐old male mechanic who sustained a TOPI involving bilateral frontal lobes with evisceration of the right eye following a workplace accident with a metal cutter. Upon arrival at the emergency department, the patient exhibited vision loss in the right eye, proptosis, and a dilated pupil. Imaging studies revealed the trajectory of a metal arrow through the right orbital roof, necessitating surgical intervention. A multidisciplinary team performed bifrontal craniectomy with duroplasty to remove the foreign body and address associated injuries. Postoperatively, the patient received broad‐spectrum antibiotics and anticonvulsants, leading to full recovery and discharge on postoperative day 10. TOPIs present unique challenges due to their rarity and potential for devastating consequences. Our case highlights the importance of timely diagnosis, meticulous surgical planning, and multidisciplinary collaboration in achieving favorable outcomes. Radiological imaging plays a crucial role in guiding treatment decisions and optimizing patient care. This report underscores the significance of early surgical intervention, antimicrobial therapy, and prophylactic measures in reducing morbidity and mortality associated with TOPIs.
Heart failure due to peripartum cardiomyopathy presenting in the first week of puerperium—A case series from Nepal
Authors: Banmala Sabin , Awal Shila , Bata Lokendra , Adhikari Priya , Basnet Sarita , Chaudhary Babita
Published: June 2024

Key Clinical Message

Peripartum cardiomyopathy (PPCM) is a rare cause of heart failure associated with pregnancy without any other known cause. With a prognosis that can vary from the complete recovery of left ventricular function to maternal mortality as well as recurrence with subsequent pregnancies, early diagnosis and treatment of PPCM is important in management. Bromocriptine treatment is beneficial effects on LVEF and mortality in women with severe acute PPCM in addition to standard heart failure therapy. However, further study is required to establish its effect in PPCM.

Peripartum cardiomyopathy (PPCM) is a rare cause of heart failure associated with pregnancy without any other known cause. Most of the clinical presentation is similar to symptoms of advanced pregnancy making the diagnosis difficult. Reported are three patients who developed dyspnea, orthopnea, and dry cough during the first week of puerperium. On examination, bilateral lower limb edema and bilateral basal lung crepitation were present in all patients. Chest radiograph showed pulmonary edema in cases two and three, and pleural effusion in case one. All patients had reduced left ventricular ejection fraction and raised N‐terminal pro‐b‐type natriuretic peptide (NT‐proBNP) levels. Case two developed PPCM in the background of left pyelonephritis. Case three was complicated by acute kidney injury. All patients were managed with bromocriptine, diuretics, beta‐blockers, ACE inhibitors, and fluid restriction. Hence, PPCM though rare should be considered as a differential in women presenting with features of heart failure in later months of pregnancy or within 5 months of delivery.
Enoyl coenzyme a hydratase 1 attenuates aortic valve calcification by suppressing Runx2 via Wnt5a/Ca2+ pathway
Authors: Rao Caijun , Liu Baoqing , Qin Haojie , Du Zhipeng
Published: June 2024

The morbidity and death rates of calcified aortic valves|calcific aortic valve (CAV) disease (CAVD) remain high for its limited therapeutic choices. Here, we investigated the function, therapeutic potential, and putative mechanisms of Enoyl coenzyme A hydratase 1 (ECH1) in CAVD by various in vitro and in vivo experiments. Single‐cell sequencing revealed that ECH1 was predominantly expressed in valve interstitial cells and was significantly reduced in CAVs. Overexpression of ECH1 reduced aortic valve calcification in ApoE−/− mice treated with high cholesterol diet, while ECH1 silencing had the reverse effect. We also identified Wnt5a, a noncanonical Wnt ligand, was also altered when ECH1 expression was modulated. Mechanistically, we found that ECH1 exerted anti‐calcific actions through suppressing Wnt signaling, since CHIR99021, a Wnt agonist, may significantly lessen the protective impact of ECH1 overexpression on the development of valve calcification. ChIP and luciferase assays all showed that ECH1 overexpression prevented Runx2 binding to its downstream gene promoters (osteopontin and osteocalcin), while CHIR99021 neutralized this protective effect. Collectively, our findings reveal a previously unrecognized mechanism of ECH1‐Wnt5a/Ca2+ regulation in CAVD, implying that targeting ECH1 may be a potential therapeutic strategy to prevent CAVD development.
Direct Methane Conversion to Acetic Acid: From Homogeneous Catalysis to Heterogeneous Catalysis
Authors: Xu Weibin , Wang Zhen , Huang Chuande , Wang Xiaodong
Published: June 2024

Direct methane conversion to acetic acid (DMCAA) offers a promising approach for transforming the abundant CH4 resources to value‐added chemicals, eliminating the multi‐step processes involving syngas generation and methanol carbonylation in traditional industrial routes. However, this reaction still faces great challenges, which primarily due to the stable C−H bond of methane and the difficulty in avoiding the over‐oxidation of products. Extensive researches have been conducted on the DMCAA process using different catalytic systems. This review summarizes the progress made in this field over the past decades and categorizes the research achievements according to homogeneous and heterogeneous systems, encompassing the investigations on catalytic mechanisms. Furthermore, the challenges and potential solutions in this field are discussed, which could provide valuable guidance for developing prospective catalysts towards DMCAA.
Constrution of Quinazoline‐Linked Covalent Organic Frameworks via a Multicomponent Reaction for Photocatalysis
Authors: Yu Song‐Chen , Li Xiaohu , Cheng Liang , Liu Li
Published: June 2024

Quinazoline (Qz)‐linked covalent organic frameworks (COFs) have been constructed via a three‐component reaction of ortho‐acylanilines, benzaldehydes and NH4OAc. The structure of Qz‐COFs has been confirmed by solid‐state nuclear magnetic resonance spectroscopy, Fourier transform infrared and powder X‐ray diffraction patterns. The Qz‐COFs possess high chemical stability, showing good endurance to strong acid, strong base, oxidant, reductant and other conditions. Particularly, Qz‐COF‐3 can catalyze the aerobic photooxidation of toluene and other compounds containing C(sp3)−H bonds.
Monogenic diabetes in a Chinese population with young‐onset diabetes: A 17‐year prospective follow‐up study in Hong Kong
Authors: Tsoi Sandra T. F. , Lim Cadmon , Ma Ronald C. W. , Lau Eric S. H. , Fan Baoqi , Chow Elaine , Kong Alice P. S. , Chan Juliana C. N. , Luk Andrea O. Y.
Published: June 2024

Aims

Asians have a high prevalence of young‐onset diabetes, but the pattern of monogenic diabetes is unknown. We aimed to determine the prevalence of monogenic diabetes in Chinese patients with young‐onset diabetes and compare the clinical characteristics and outcome between patients with and without monogenic diabetes.

Materials and Methods

We sequenced a targeted panel of 33 genes related to monogenic diabetes in 1021 Chinese patients with non‐type 1 diabetes diagnosed at age ≤40 years. Incident complications including cardiovascular disease (CVD), end‐stage kidney disease (ESKD) and all‐cause death were captured since enrolment (1995–2012) until 2019.

Results

In this cohort (mean ± SD age at diagnosis: 33.0 ± 6.0 years, median[IQR] diabetes duration 7.0[1.0–15.0] years at baseline, 44.9% men), 22(2.2%, 95% confidence interval[CI] 1.4%–3.2%) had monogenic diabetes. Pathogenic (P) or likely pathogenic (LP) variants were detected in GCK (n = 6), HNF1A (n = 9), HNF4A (n = 1), PLIN1 (n = 1) and PPARG (n = 2), together with copy number variations in HNF1B (n = 3). Over a median follow‐up of 17.1 years, 5(22.7%) patients with monogenic diabetes (incidence rate 12.3[95% CI 5.1–29.4] per 1000 person‐years) versus 254(25.4%) without monogenic diabetes (incidence rate 16.7[95% CI 14.8–18.9] per 1000 person‐years) developed the composite outcome of CVD, ESKD and/or death (p = 0.490). The multivariable Cox model did not show any difference in hazards for composite events between groups.

Conclusions

In Chinese with young‐onset non‐type 1 diabetes, at least 2% of cases were contributed by monogenic diabetes, over 80% of which were accounted for by P/LP variants in common MODY genes. The incidence of diabetes complications was similar between patients with and without monogenic diabetes.
Proteomic profiling of TBC1 domain family member 21‐null sperms reveals the critical roles of TEKT 1 in their tail defects
Authors: Pan Pei‐Yi , Ke Chih‐Chun , Wang Ya‐Yun , Lin Yu‐Hua , Ku Wei‐Chi , Au Chin‐Fong , Chan Chying‐Chyuan , Huang Chia‐Yen , Lin Ying‐Hung
Published: June 2024

Background

Approximately 7% of the males exhibit reduced fertility; however, the regulatory genes and pathways involved remain largely unknown. TBC1 domain family member 21 (TBC1D21) contains a conserved RabGAP catalytic domain that induces GDP/GTP exchange to inactivate Rabs by interacting with microtubules. We previously reported that Tbc1d21‐null mice exhibit severe sperm tail defects with a disrupted axoneme, and that TBC1D21 interacts with RAB10. However, the pathological mechanisms underlying the Tbc1d21 loss‐induced sperm tail defects remain unknown.

Results

Murine sperm from wild‐type and Tbc1d21‐null mice were comparatively analyzed using proteomic assays. Over 1600 proteins were identified, of which 15 were significantly up‐regulated in Tbc1d21‐null sperm. Notably, several tektin (TEKT) family proteins, belonging to a type of intermediate filament critical for stabilizing the microtubular structure of cilia and flagella, were significantly up‐regulated in Tbc1d21−/− sperm. We also found that TBC1D21 interacts with TEKT1. In addition, TEKT1 co‐localized with RAB10 during sperm tail formation. Finally, we found Tbc1d21‐null sperm exhibited abnormal accumulation of TEKT1 in the midpiece region, accompanied by disrupted axonemal structures.

Conclusions

These results reveal that TBC1D21 modulates TEKTs protein localization in the axonemal transport system during sperm tail formation.
Investigating pelagic biodiversity and gelatinous zooplankton communities in the rapidly changing European Arctic: An eDNA metabarcoding survey
Authors: Murray Ayla , Priest Taylor , Antich Adria , von Appen Wilken‐Jon , Neuhaus Stefan , Havermans Charlotte
Published: June 2024

Fram Strait, the gateway between the Arctic and Atlantic Oceans, is undergoing major climate change‐induced physical and biological transformations. In particular, rapid warming and ongoing “Atlantification” are driving species range shifts and altering food web structures in the Arctic. Understanding and predicting the consequences of these processes on future ecosystems requires detailed assessments of local and pelagic biodiversity. Gelatinous zooplankton (GZP) is an important component of pelagic communities, and recent evidence indicates that such communities are undergoing major changes in the Fram Strait. However, as sampling GZP is challenging, they are regularly underestimated in biodiversity, distribution, and abundance. To overcome this and address existing ecological knowledge gaps, we investigated patterns of pelagic metazoan diversity in Fram Strait using environmental DNA (eDNA) metabarcoding of the cytochrome c oxidase I (COI) gene. We successfully detected a broad range of taxa from the marine metazoan and GZP communities across sampling locations and ocean depth zones. We demonstrate the vertical structuring of diversity and elucidate relationships between taxa and water mass indicators, such as salinity and temperature. Furthermore, when comparing eDNA data with net and video transect data for GZP at the same period and location, we found that eDNA uncovered a higher number of taxa, including several that were not detected by the other methods. This study is a contribution to the formation of baseline Arctic GZP biodiversity datasets, as well as future research on changing marine metazoan biodiversity and community composition.
Surface Coating Enabling Sulfide Solid Electrolytes with Excellent Air Stability and Lithium Compatibility
Authors: Luo Min , Wang Changhong , Duan Yi , Zhao Xuyang , Wang Jiantao , Sun Xueliang
Published: June 2024

All‐solid‐state lithium metal batteries (ASSLMBs) featuring sulfide solid electrolytes (SEs) are recognized as the most promising next‐generation energy storage technology because of their exceptional safety and much‐improved energy density. However, lithium dendrite growth in sulfide SEs and their poor air stability have posed significant obstacles to the advancement of sulfide‐based ASSLMBs. Here, a thin layer (approximately 5 nm) of g‐C3N4 is coated on the surface of a sulfide SE (Li6PS5Cl), which not only lowers the electronic conductivity of Li6PS5Cl but also achieves remarkable interface stability by facilitating the in situ formation of ion‐conductive Li3N at the Li/Li6PS5Cl interface. Additionally, the g‐C3N4 coating on the surface can substantially reduce the formation of H2S when Li6PS5Cl is exposed to humid air. As a result, Li–Li symmetrical cells using g‐C3N4‐coated Li6PS5Cl stably cycle for 1000 h with a current density of 0.2 mA cm−2. ASSLMBs paired with LiNbO3‐coated LiNi0.6Mn0.2Co0.2O2 exhibit a capacity of 132.8 mAh g−1 at 0.1 C and a high‐capacity retention of 99.1% after 200 cycles. Furthermore, g‐C3N4‐coated Li6PS5Cl effectively mitigates the self‐discharge behavior observed in ASSLMBs. This surface‐coating approach for sulfide solid electrolytes opens the door to the practical implementation of sulfide‐based ASSLMBs.
Heart Failure score and outcomes in patients with preserved ejection fraction after catheter ablation for atrial fibrillation
Authors: Sumiyoshi Hironobu , Tasaka Hiroshi , Yoshida Kenta , Yoshino Mitsuru , Kadota Kazushige
Published: June 2024

Aims

Atrial fibrillation (AF) is frequently associated with heart failure with preserved ejection fraction (HFpEF), but the diagnosis and prediction of the outcomes of HFpEF are difficult. Notably, the Heart Failure Association of the European Society of Cardiology proposed the use of the HFA–PEFF score in the diagnosis of HFpEF. This study aimed to assess the prognostic value of the pre‐ and post‐procedural HFA–PEFF scores in patients with preserved ejection fraction (EF) after catheter ablation (CA) for AF. The primary endpoint was a composite of cardiac hospitalization for cardiovascular events and all‐cause mortality. The secondary endpoint was AF recurrence.

Methods and results

Overall, 354 patients with AF and preserved EF who underwent CA as well as blood tests and transthoracic echocardiography 2 weeks before and 6 months after CA from January 2018 to December 2019 were retrospectively enrolled in the study.

In the 354 participants, univariate analysis showed that the post‐procedural HFA–PEFF score was associated with a 3‐year risk of the primary endpoint (hazard ratio [HR] = 3.73; 95% confidence interval [CI] = 2.07–6.73; P < 0.001), whereas the pre‐procedural HFA–PEFF score was not (HR = 1.24, 95% CI = 0.82–1.86, P = 0.307). Further, the association between the post‐procedural HFA–PEFF score and primary endpoint was not modified even after including other relevant variables into the score. Similar to the primary endpoint, the post‐procedural HFA–PEFF score was associated with the 3‐year risk of AF recurrence (P < 0.001).

Conclusions

In patients with preserved EF undergoing AF ablation, the HFA–PEFF score at 6 months after CA was associated with the primary endpoint and AF recurrence at the 3‐year follow‐up.