bluuebunny/crossref_metadata_2025_split huggingface dataset:
Are we prepared to deliver gene‐targeted therapies for rare diseases?
Authors: Yu Timothy W. , Kingsmore Stephen F. , Green Robert C. , MacKenzie Tippi , Wasserstein Melissa , Caggana Michele , Gold Nina B. , Kennedy Annie , Kishnani Priya S. , Might Matthew , Brooks Phillip J. , Morris Jill A. , Parisi Melissa A. , Urv Tiina K. 
Published: January 2023

AbstractThe cost and time needed to conduct whole‐genome sequencing (WGS) have decreased significantly in the last 20 years. At the same time, the number of conditions with a known molecular basis has steadily increased, as has the number of investigational new drug applications for novel gene‐based therapeutics. The prospect of precision gene‐targeted therapy for all seems in reach… or is it? Here we consider practical and strategic considerations that need to be addressed to establish a foundation for the early, effective, and equitable delivery of these treatments.
Blood pH and COVID‐19
Authors: Elsebai Mahmoud Fahmi , Habib EL‐Sayed E. 
Published: January 2023

AbstractThe coronavirus disease 2019 (COVID‐19) pandemic is a worldwide war. Raising the blood pH might be a crucial strategy to chase COVID‐19. The human blood is slightly alkaline, which is essential for cell metabolism, normal physiology, and balanced immunity since all of these biological processes are pH‐dependent. Varieties of physiologic derangements occur when the blood pH is disrupted. Severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) proliferates in acidic blood that magnifies the severity of COVID‐19. On the other side, blood acidemia is linked to increased morbidity and mortality because of its complications on immunity, especially in the elderly and in critical diseases such as cancer, musculoskeletal degradation, renal, cardiac, and pulmonary disorders, which result in many pathological disorders such as osteomalacia, and disturbing the hematopoiesis. Additionally, acidemia of the blood facilitates viral infection and progression. Thus, correcting the acid–base balance might be a crucial strategy for the treatment of COVID‐19, which might be attributed to the distraction of the viral spike protein to its cognate receptor angiotensin‐converting enzyme 2 and supporting the over‐taxed immunity.
Weaker face recognition in adults with autism arises from perceptually based alterations
Authors: Hartston Marissa , Avidan Galia , Pertzov Yoni , Hadad Bat‐Sheva 
Published: January 2023

AbstractFace recognition has been shown to be impaired in autism spectrum disorders (ASD). However, it is still debated whether these face processing deficits arise from perceptually based alterations. We tested individuals with ASD and matched typically developing (TD) individuals using a delayed estimation task in which a single target face was shown either upright or inverted. Participants selected a face that best resembled the target face out of a cyclic space of morphed faces. To enable the disentanglement of visual from mnemonic processing, reports were required either following a 1 and 6 second retention interval, or simultaneously while the target face was still visible. Individuals with ASD made significantly more errors than TD individuals in both the simultaneous and delayed intervals, indicating that face recognition deficits in autism are also perceptual rather than strictly memory based. Moreover, individuals with ASD exhibited weaker inversion effects than the TD individuals, on all retention intervals. This finding, that was mostly evident in precision errors, suggests that contrary to the more precise representations of upright faces in TD individuals, individuals with ASD exhibit similar levels of precision for inverted and upright faces, for both simultaneous and delayed conditions. These results suggest that weakened memory for faces reported in ASD may be secondary to an underlying perceptual deficit in face processing.
Thionin as a Bipolar Organic Cathode Material for Aqueous Rechargeable Zinc Batteries
Authors: Yu Pu , Wang Junxiao , Gan Xiaotang , Guo Zhihua , Huang Liang , Song Zhiping 
Published: January 2023

AbstractOrganic cathode materials (OCMs) have been widely applied in aqueous rechargeable zinc batteries (ARZBs), but there are still many novel structures to be explored for better electrochemical performance and clearer mechanism. Herein, we have studied an organic biological dye, namely thionin (Thn‐CH3COO), as a bipolar‐type OCM for ARZBs based on its electroactive phenothiazine unit. In the optimal electrolyte of 2 M Zn(CF3SO3)2, Thn‐CH3COO exhibited the lowest solubility and thus the highest cycling stability (94 % capacity retention after 100 cycles), with a reversible capacity of 162 mAh g−1 (the theoretical value is 186 mAh g−1) and a discharge plateau at ∼0.8 V vs. Zn2+/Zn. Various characterization and DFT calculations have revealed that both CH3COO− and CF3SO3− anions and H+ cations participated the p‐type and n‐type reactions, respectively. In brief, the novel structure, competitive performance, and exhaustive mechanism investigation will facilitate the further development of ARZBs based on OCMs.
Recent advances in the in vitro and in vivo methods to assess impact of P‐glycoprotein and breast cancer resistance protein transporters in central nervous system drug disposition
Authors: Chatterjee Sagnik , Deshpande Anup Arunrao , Shen Hong 
Published: January 2023

AbstractOne challenge in central nervous system (CNS) drug discovery has been ensuring the blood–brain barrier (BBB) penetration of compounds at an efficacious concentration that provides suitable safety margins for clinical investigation. Research providing for the accurate prediction of brain penetration of compounds during preclinical discovery is important to a CNS program. In the BBB, P‐glycoprotein (P‐gp) (ABCB1) and breast cancer resistance protein (BCRP) (ABCG2) transporters have been demonstrated to play a major role in the active efflux of endogenous compounds and xenobiotics out of the brain microvessel cells and back to the systemic circulation. In the past 10 years, there has been significant technological improvement in the sensitivity of quantitative proteomics methods, in vivo imaging, in vitro methods of organoid and microphysiological systems, as well as in silico quantitative physiological based pharmacokinetic and systems pharmacology models. Scientists continually leverage these advancements to interrogate the distribution of compounds in the CNS which may also show signals of substrate specificity of P‐gp and/or BCRP. These methods have shown promise toward predicting and quantifying the unbound concentration(s) within the brain relevant for efficacy or safety. In this review, the authors have summarized the in vivo, in vitro, and proteomics advancements toward understanding the contribution of P‐gp and/or BCRP in restricting the entry of compounds to the CNS of either healthy or special populations. Special emphasis has been provided on recent investigations on the application of a proteomics‐informed approach to predict steady‐state drug concentrations in the brain. Moreover, future perspectives regarding the role of these transporters in newer modalities are discussed.
Innervation of the heart: Anatomical study with application to better understanding pathologies of the cardiac autonomics
Authors: González Mailén L. , Pividori Sofía M. , Fosser Gregorio , Pontecorvo Agustina A. , Franco‐Riveros Verena B. , Tubbs Richard Shane , Boezaart André P. , Reina Miguel A. , Buchholz Bruno 
Published: January 2023

AbstractCurrent advances in management of the cardiac neuroaxis in different cardiovascular diseases require a deeper knowledge of cardiac neuroanatomy. The aim of the study was to increase knowledge of the human fetal extrinsic cardiac nervous system. We achieved this by systematizing the origin and formation of the cardiac nerves, branches, and ganglia and their sympathetic/parasympathetic connections. Thirty human fetuses (60 sides) were subjected to detailed sub‐macroscopic dissection of the cervical and thoracic regions. Cardiac accessory ganglia lying on a cardiac nerve or in conjunction with two or more (up to four) nerves before entering the mediastinal cardiac plexus were observed in 13 sides. Except for the superior cardiac nerve, the sympathetic cardiac nerves were individually variable and inconstant. In contrast, the cardiac branches of the vagus nerve appeared grossly more constant and invariable, although the individual cardiac branches varied in number and position of origin. Each cervical cardiac nerve or cardiac branch of the vagus nerve could be singular or multiple (up to six) and originated from the sympathetic trunk or the vagus nerve by one, two, or three roots. Sympathetic nerves arose from the cervical‐thoracic ganglia or the interganglionic segment of the sympathetic trunk. Connections were found outside the cardiac plexus. Some cardiac nerves were connected to non‐cardiac nerves, while others were connected to each other. Common sympathetic/parasympathetic cardiac nerve trunks were more frequent on right (70%) versus left sides (20%). The origin, frequency, and connections of the cardiac nerves and branches are highly variable in the fetus. Detailed knowledge of the normal neuroanatomy of the heart could be useful during cardiac neuromodulation procedures and in better understanding nervous pathologies of the heart.
GC/MS Profiling and Evaluation of Leaf Essential Oil for Bactericidal Effect and Free Radical Scavenging Activity of Plectranthus amboinicus (Lour.) Spreng Collected from Odisha, India
Authors: Jena Biswajit , Biswal Bhagyashree , Sarangi Ashirbad , Giri Alok Kumar , Bhattacharya Debapriya , Acharya Laxmikanta 
Published: January 2023

AbstractPlectranthus amboinicus (Lour.) Spreng, known as the Indian borage or Mexican mint, is one of the most documented species in the family Lamiaceae for its therapeutic and pharmaceutical values. It is found in the tropical and subtropical regions of the world. The leaf essential oil has immense medicinal benefits like treating illnesses of the skin and disorders like colds, asthma, constipation, headaches, coughs, and fevers. After analyzing earlier reports with regard to the quantity and quality of leaf oil yield, we discovered that the germplasm taken from Odisha is preferable to other germplasms. The objective of the present work is to evaluate the free radical scavenging activity and bactericidal effect of leaf essential oil (EO) of Plectranthus amboinicus (Lour.) Spreng collected from the state of Odisha, India. The hydro distillation technique has been used for essential oil extraction. Upon GC/MS analysis, approximately 57 compounds were identified with Carvacrol as the major compound (peak area=20.25 %), followed by p‐thymol (peak area=20.17 %), o‐cymene (peak area=19.41 %) and carene (peak area=15.89 %). On evaluation of free radical scavenging activity, it was recorded that the best value of inhibitory concentration, was for DPPH with IC50=18.64 ppm and for H2O2 with IC50=9.35 ppm. The EO showed efficient bactericidal effect against both gram positive (Mycobacterium smegmatis, Staphylococcus aureus, Enterococcus faecium) and gram negative (Escherichia coli, Vibrio cholerae, Klebsiella pneumoniae) bacteria studied through well diffusion method. Fumigatory action of the essential oil was found against M. smegmatis, the model organism for tuberculosis study. Alamar Blue assay, gave a result with MIC value for M. smegmatis i. e., 0.12 μg/ml and the MBC value of 0.12 μg/ml. Hence, P. amboinicus found in Odisha can be suggested as an elite variety and should be further investigated for efficient administration in drug formulation.
Impact of complex percutaneous coronary intervention features on clinical outcomes in patients with or without chronic kidney disease
Authors: Chen Huazhen , Spirito Alessandro , Sartori Samantha , Nicolas Johny , Cao Davide , Zhang Zhongjie , Baber Usman , Kamaleldin Karim , Guthrie Jeffers , Vogel Birgit , Sweeny Joseph , Krishnan Prakash , Sharma Samin K. , Kini Annapoorna , Dangas George , Mehran Roxana 
Published: January 2023

AbstractBackgroundPatients with chronic kidney disease (CKD) are at higher risk of ischemic and bleeding events after percutaneous coronary intervention (PCI). Complex PCI (CPCI) is associated with higher rates of ischemic complications. Whether CPCI confers an additive risk of adverse events in CKD patients is unclear.MethodsPatients who underwent PCI at a single tertiary‐care‐center between 2012 and 2019 were stratified by CKD status and CPCI. The primary outcome was major adverse cardiac events (MACE), a composite of all‐cause death, myocardial infarction (MI), and target‐vessel revascularization (TVR) at 1‐year follow‐up. Secondary outcomes included the individual components of the primary outcome and major bleeding.ResultsOut of 15,071 patients, 4537 (30.1%) had CKD and 10,534 (69.9%) had no CKD. Patients undergoing CPCI were 1151 (25.4%) and 2983 (28.3%) in the two cohorts, respectively. At one year, CPCI compared with no CPCI was associated with higher risk of MACE in both CKD (Adj. HR 1.72, 95% confidence interval [CI] 1.45−2.06, p < 0.001) and no‐CKD patients (Adj. hazard ratios [HR] 2.19, 95% CI 1.91−2.51, p < 0.001; p of interaction 0.057), determined by an excess of death, MI and TVR in CKD patients and of TVR and MI only in no‐CKD. CPCI was related with a consistent increase of major bleeding in the CKD (Adj. HR 1.49, 95% CI 1.18−1.87, p < 0.001) and no‐CKD group (Adj. HR 1.23, 95% CI 0.98−1.54, p = 0.071, p of interaction 0.206).ConclusionAt 1‐year follow‐up, CPCI was associated with higher risk of MACE and major bleeding irrespective of concomitant CKD. CPCI predicted mortality in CKD patients only.
Insights from a rare myeloproliferative neoplasm with coexisting BCR‐ABL1 fusion gene, CALR, and TET2 mutations treated with nilotinib and ruxolitinib
Authors: Huo Li , Xie Jundan , Wang Qian , Shen Hongjie , Ding Zixuan , Wen Lijun , Zeng Zhao , Xu Yi , Ruan Changgeng , Chen Suning , Xue Mengxing 
Published: January 2023

AbstractMyeloproliferative neoplasms (MPNs) with concurrent BCR‐ABL1 fusion gene and CALR mutation are especially rare. We report a patient with coexisting BCR‐ABL1 fusion gene, CALR, and TET2 mutations who was treated with the combination of the second‐generation TKI nilotinib and JAK1/JAK2 inhibitor ruxolitinib.
Healing of large endodontic lesions using a new combination of triple antibiotics: A case report
Authors: Asgary Saeed , Parhizkar Ardavan 
Published: January 2023

AbstractIn the case report presented, three cases of large endodontic lesions, which were the consequences of endodontic treatment failure, were studied. In all cases, a novel combination of triple antibiotics was used to successfully manage and heal the lesions, showing the promising potential of the antibiotic combination in resolving pathosis.
Non‐Isothermal Mass Transfer in Fluid Drops with Internal Circulation
Authors: Binu T. V. , Jayanti Sreenivas 
Published: January 2023

AbstractThe influence of internal circulation on the heat and mass transfer within dispersed fluid drops in translation was studied numerically using the computational fluid dynamics simulation tool ANSYS FLUENT. The three phases identified for heat/mass transfer are: the initial and final diffusion‐dominated phases and a middle convection‐dominated phase. Non‐isothermal mass transfer simulations using temperature‐dependent diffusion coefficients were carried out to investigate the influence of heating and cooling of the drop on the solute transfer. Mass transfer is slower compared to heat transfer and the final diffusion‐dominated mass transfer occurs at the final temperature attained by the drop. Mass transfer is faster for drop heating than for drop cooling, as the final diffusion phase is rate controlling and significant solute transfer occurs at the final higher temperature.
Columnar Liquid Crystalline Glasses by Combining Configurational Flexibility with Moderate Deviation from Planarity: Extended Triaryltriazines
Authors: Nunes da Silva Fabrícia , Marchi Luciano Hugo , Stadtlober Carlos H. , Farias Giliandro , Durola Fabien , Eccher Juliana , Bechtold Ivan H. , Bock Harald , Gallardo Hugo , Vieira André A. 
Published: January 2023

AbstractTriply phenanthryl‐ and tetrahelicenyl‐substituted triazine‐hexaalkyl esters with short alkyl chains show glass transitions conveniently above room temperature within the hexagonal columnar liquid crystalline state, resulting in a solid columnar order at room temperature. As the hexagonal columnar mesophase is easily aligned with the director perpendicular to a solid substrate, such glassy columnar liquid matrices are aimed at for the orientation of guest emitters, to obtain anisotropic emission. A condition for face‐on alignment on substrates are attainable melting and clearing temperatures, which is achieved with the moderately nonplanar tetrahelicenyl derivatives in spite of their short alkyl periphery. An unusual phase transition between two columnar mesophases of same hexagonal symmetry, but very different long‐distance regularity of the column lattice, is found in one phenanthryl homolog.
Melt Castable Derivatives of Pentaerythritol Tetranitrate
Authors: Benz Maximilian , Klapötke Thomas M. , Kölbl Niklas , Kuch Jürgen , Lenz Tobias , Parigi Ersel , Stierstorfer Jörg 
Published: January 2023

AbstractIn the search for high‐performance and environmentally friendly energetic materials, the derivatization of known materials is an often‐applied concept to fulfill modern‐day demands. Surprisingly, the long know pentaerythritol tetranitrate (PETN) has only been derivatized to a limited extent. PETN shows a brought application in energetic materials or pharmaceutics. In this work, the PETN backbone is modified by introducing nitramine, ionic nitramine, amine, ionic amine and tetrazole functionalities. The obtained and structurally similar compounds allow good comparability and insights into functional group effects on sensitivity, thermal behavior and performance. The functionalizations result in melting points in the range of 64 to 126 °C. Some compounds are therefore potential candidates to replace toxic TNT.
Ultrafast Electron Transfer Dynamics of Organic Polymer Nanoparticles with Graphene Oxide
Authors: Li Dong , He Xiaoxiao , Zhao Litao , Jia Menghui , Li Haoyang , Zhang Sanjun , Zhang Xiaolei , Chen Jinquan , Jin Qingyuan , Xu Jianhua 
Published: January 2023

AbstractWe prepared organic polymer poly‐3‐hexylthiophene (p3ht) nanoparticles (NPs) and graphene oxide (GO)/reduced graphene oxide (RGO) composites p3ht NPs‐GO/RGO by using the reprecipitation method. We demonstrated that GO/RGO could improve the ordering and planarity of p3ht chains as well as the formation of p3ht NPs, and confirmed the effects of GO/RGO on the fluorescence and carrier transport dynamics of p3ht NPs by using femtosecond fluorescence upconversion and transient absorption (TA) techniques. Ultrafast electron transfer (∼1 ps) between GO/RGO and p3ht NPs quenched the fluorescence of p3ht NPs, indicating excellent properties of p3ht NPs‐GO/RGO as the charge transfer complexes. Efficient electron transfer may promote the applications of p3ht NPs‐GO/RGO composites in organic polymer solar cells and photocatalysis. Moreover, RGO had stronger interfacial interactions and more matched conduction band energy levels with p3ht NPs than GO did, which implied that p3ht NPs‐RGO might have greater application values than p3ht NPs‐GO.
Total Syntheses of Favolasins A, E, G and K, Polyketides Isolated from Cultures of the Basidiomycetes Fungi Favolaschia sp. BCC 18686 and Favolaschia caloceraBCC 36684
Authors: Sheng Bingbing , Lan Ping , Kiong Jolynn , Khalil Zeinab G. , Capon Robert J. , Banwell Martin G. 
Published: January 2023

Comprehensive SummaryThe structures assigned to all four members, 1—4, of the recently reported favolasin class of natural product have been prepared for the first time by chemical synthesis. Suzuki‐Miyaura cross‐coupling chemistry was used to establish the associated biaryl substructures. The key step used in preparing the 1,5‐benzodioxepin ring system associated with compounds 3 and 4 was the acid‐catalyzed 7‐exo‐tet cyclization of an appropriately substituted 2‐(oxiran‐2‐ylmethoxy)phenol while a base‐promoted 6‐exo‐tet cyclization of the same substrate was used to construct the 2,3‐dihydrobenzo[b][1,4]dioxine core of target 2. The spectral data derived from the four synthetically‐produced favolasins matched those reported for the corresponding natural products. Preliminary biological screening of compounds 1—3 as well as a suite of fourteen precursors reveal that they display no notable anti‐bacterial, anti‐fungal or anti‐tumor activities but congener K (4) is active, in the mM range, against Plasmodium falciparum.
Association of polypharmacy and potential drug‐drug interactions with adverse treatment outcomes in older adults with advanced cancer
Authors: Mohamed Mostafa R. , Mohile Supriya G. , Juba Katherine M. , Awad Hala , Wells Megan , Loh Kah Poh , Flannery Marie , Culakova Eva , Tylock Rachael G. , Ramsdale Erika E. 
Published: January 2023

AbstractBackgroundPolypharmacy is common in older adults who are starting cancer treatment and is associated with an increased risk of potentially inappropriate medications (PIMs) and potential drug‐drug interactions (PDIs). The authors evaluated the association of medication measures with adverse outcomes in older adults with advanced cancer who were receiving systemic therapy.MethodsThis secondary analysis from GAP 70+ Trial (ClinicalTrials.gov identifier NCT02054741; principal investigator, Supriya G. Mohile) enrolled patients aged 70 years and older with advanced cancer who planned to start a new treatment regimen (n = 718). Polypharmacy was assessed before the initiation of treatment and was defined as the concurrent use of eight or more medications. PIMs were categorized using 2019 Beers Criteria and the Screening Tool of Older Persons' Prescriptions. PDIs were evaluated using Lexi‐Interact Online. Study outcomes were assessed within 3 months of treatment and included: (1) the number of grade ≥2 and ≥3 toxicities according to the National Cancer Institute Common Toxicity Criteria, (2) treatment‐related unplanned hospitalization, and (3) early treatment discontinuation. Multivariable regression models examined the association of medication measures with outcomes.ResultsThe mean patient age was 77 years, and 57% had lung or gastrointestinal cancers. The median number of medications was five (range, 0–24 medications), 28% of patients received eight or more medications, 67% received one or more PIM, and 25% had one or more major PDI. The mean number of grade ≥2 toxicities in patients with polypharmacy was 9.8 versus 7.7 in those without polypharmacy (adjusted β = 1.87; standard error, 0.71; p <.01). The mean number of grade ≥3 toxicities in patients with polypharmacy was 2.9 versus 2.2 in patients without polypharmacy (adjusted β = 0.59; standard error, 0.29; p = .04). Patients with who had one or more major PDI had 59% higher odds of early treatment discontinuation (odds ratio, 1.59; 95% confidence interval, 1.03–2.46; p = .03).ConclusionsIn a cohort of older adults with advanced cancer, polypharmacy and PDIs were associated with an increased risk of adverse treatment outcomes. Providing meaningful screening and interventional tools to optimize medication use may improve treatment‐related outcomes in these patients.