bluuebunny/crossref_metadata_2025_split huggingface dataset:
SARS‐CoV‐2 infection triggers more potent antibody‐dependent cellular cytotoxicity (ADCC) responses than mRNA‐, vector‐, and inactivated virus‐based COVID‐19 vaccines
Authors: Zedan Hadeel T. , Smatti Maria K. , Al‐Sadeq Duaa W. , Al Khatib Hebah A. , Nicolai Eleonora , Pieri Massimo , Bernardini Sergio , Hssain Ali Ait , Taleb Sara , Qotba Hamda , Issa Khodr , Abu Raddad Laith J. , Althani Asmaa A. , Nasrallah Gheyath K. , Yassine Hadi M. 
Published: March 2024

AbstractNeutralizing antibodies (NAbs) are elicited after infection and vaccination and have been well studied. However, their antibody‐dependent cellular cytotoxicity (ADCC) functionality is still poorly characterized. Here, we investigated ADCC activity in convalescent sera from infected patients with wild‐type (WT) severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) or omicron variant compared with three coronavirus disease 2019 (COVID‐19) vaccine platforms and postvaccination breakthrough infection (BTI). We analyzed ADCC activity targeting SARS‐CoV‐2 spike (S) and nucleocapsid (N) proteins in convalescent sera following WT SARS‐CoV‐2‐infection (n = 91), including symptomatic and asymptomatic infections, omicron‐infection (n = 8), COVID‐19 vaccination with messenger RNA‐ (mRNA)‐ (BNT162b2 or mRNA‐1273, n = 77), adenovirus vector‐ (n = 41), and inactivated virus‐ (n = 46) based vaccines, as well as post‐mRNA vaccination BTI caused by omicron (n = 28). Correlations between ADCC, binding, and NAb titers were reported. ADCC was elicited within the first month postinfection and ‐vaccination and remained detectable for ≥3 months. WT‐infected symptomatic patients had higher S‐specific ADCC levels than asymptomatic and vaccinated individuals. Also, no difference in N‐specific ADCC activity was seen between symptomatic and asymptomatic patients, but the levels were higher than the inactivated vaccine. Notably, omicron infection showed reduced overall ADCC activity compared to WT SARS‐CoV‐2 infection. Although post‐mRNA vaccination BTI elicited high levels of binding and NAbs, ADCC activity was significantly reduced. Also, there was no difference in ADCC levels across the four vaccines, although NAbs and binding antibody titers were significantly higher in mRNA‐vaccinated individuals. All evaluated vaccine platforms are inferior in inducing ADCC compared to natural infection with WT SARS‐CoV‐2. The inactivated virus‐based vaccine can induce N‐specific ADCC activity, but its relevance to clinical outcomes requires further investigation. Our data suggest that ADCC could be used to estimate the extra‐neutralization level against COVID‐19 and provides evidence that vaccination should focus on other Fc‐effector functions besides NAbs. Also, the decreased susceptibility of the omicron variant to ADCC offers valuable guidance for forthcoming efforts to identify the specific targets of antibodies facilitating ADCC.
Longitudinal analysis of CSF HIV RNA in untreated people with HIV: Identification of CSF controllers
Authors: Trunfio Mattia , Tang Bin , Okwuegbuna Oluwakemi , Iudicello Jennifer E. , Bharti Ajay , Moore David J. , Gelman Benjamin B. , Morgello Susan , Patel Payal B. , Rubin Leah H. , Ances Beau M. , Gianella Sara , Heaton Robert K. , Ellis Ronald J. , Letendre Scott L. 
Published: March 2024

AbstractInterindividual variation of human immunodeficiency virus (HIV) RNA setpoint in cerebrospinal fluid (CSF) and its determinants are poorly understood, but relevant for HIV neuropathology, brain reservoirs, viral escape, and reseeding after antiretroviral interruptions. Longitudinal multicentric study on demographic, clinical, and laboratory correlates of CSF HIV RNA in 2000 follow‐up visits from 597 people with HIV (PWH) off antiretroviral therapy (ART) and with plasma HIV RNA > the lower limit of quantification (LLQ). Factors associated with CSF control (CSFC; CSF HIV RNA < LLQ while plasma HIV RNA > LLQ) and with CSF/plasma discordance (CSF > plasma HIV RNA > LLQ) were also assessed through mixed‐effects models. Posthoc and sensitivity analyses were performed for persistent CSFC and ART‐naïve participants, respectively. Over a median follow‐up of 2.1 years, CSF HIV RNA was associated with CD4+ and CD8+ T cells, CSF leukocytes, blood–brain barrier (BBB) integrity, biomarkers of iron and lipid metabolism, serum globulins, past exposure to lamivudine, and plasma HIV RNA (model p < 0.0001). CSFC (persistent in 7.7% over 3 years) and CSF/plasma discordance (persistent in <0.01% over 1 year) were variably associated with the same parameters (model p < 0.001). Sensitivity analyses confirmed most of the previous associations in participants never exposed to ART. Persistent CSFC was associated with higher CD4+ T‐cell count nadir (p < 0.001), lower serum globulins (p = 0.003), and lower CSF leukocytes (p < 0.001). Without ART, one in 13 PWH had persistently undetectable CSF HIV RNA, while persistent CSF/plasma discordance was extremely rare over years. Immune responses, inflammation, BBB permeability, and iron and lipid metabolism were all associated with HIV replication in CSF.
Identification of inositol monophosphatase as a broad‐spectrum antiviral target of ivermectin
Authors: Jitobaom Kunlakanya , Peerapen Paleerath , Boonyuen Usa , Meewan Ittipat , Boonarkart Chompunuch , Sirihongthong Thanyaporn , Thongon Songkran , Thongboonkerd Visith , Auewarakul Prasert 
Published: March 2024

AbstractIvermectin has broad‐spectrum antiviral activities. Despite the failure in clinical application of COVID‐19, it can serve as a lead compound for the development of more effective broad‐spectrum antivirals, for which a better understanding of its antiviral mechanisms is essential. We thus searched for potential novel targets of ivermectin in host cells by label‐free thermal proteomic profiling using Huh‐7 cells. Inositol monophosphatase (IMPase) was found among the proteins with shifted thermal stability by ivermectin. Ivermectin could inhibit IMPase activity and reduce cellular myo‐inositol and phosphatidylinositol‐4‐phosphate levels. On the other hand, inositol could impair the antiviral activity of ivermectin and lithium, an IMPase inhibitor with known antiviral activity. As phosphatidylinositol phosphate is crucial for the replication of many RNA viruses, inhibition of cellular myo‐inositol biosynthesis may be an important antiviral mechanism of ivermectin. Hence, inhibition of IMPase could serve as a potential target for broad‐spectrum antiviral development.
Epidemiological characteristics of Epstein‐Barr virus infection in children and distribution of disease spectrum in hospitalized patients in shandong province
Authors: Wu Dan , Wang Juan , Zeng Qian , Wang Ling , Lv Xin 
Published: March 2024

AbstractThis study aims to investigate the epidemiological characteristics of Epstein‐Barr virus (EBV) infection in children and the distribution of disease spectrum in hospitalized patients in Shandong Province. A retrospective analysis was conducted on the clinical data of children with EBV infection admitted to hospitals in Shandong Province from January 2022 to December 2022. The epidemiological characteristics, including age, gender, and clinical manifestations, were analyzed. The detection rate of EBV antibodies and the seropositivity rates of different antibodies were also examined. A total of 7124 children with EBV infection were included in this study, with an average age of 7.5 years. The male‐to‐female ratio was 1.43:1. Among the patients, the positive detection rate of EBV antibodies was 78.40%. The seropositivity rate of Epstein‐Barr viral capsid antigen‐Immunoglobin G antibodies was 57.09%. The highest incidence of EBV infection was observed in the age group 36−72 months. The urban positive rate was higher than that in rural areas. EBV infection in children in Shandong Province exhibits specific epidemiological characteristics, with a higher incidence in the age group of 36−72 months. Fever, sore throat, and fatigue are the main clinical manifestations. The detection rate of EBV antibodies is relatively high among hospitalized patients. These findings provide valuable information for controlling the transmission of children with suspected Epstein‐Barr virus infection.
Significant difference in femoral torsion between coronal plane alignment of the knee type 1 and 4
Authors: Ziegenhorn Jonas , Kirschberg Julia , Heinecke Markus , von Eisenhart‐Rothe Rüdiger , Matziolis Georg 
Published: March 2024

AbstractPurposeThe purpose of this study was to find out whether the torsions of the femur and tibia are dependent on the coronal plane alignment of the knee (CPAK) type.MethodsFive hundred patients (1000 legs) were included, who received a whole leg standing three‐dimensional (3D) radiograph using EOS imaging (EOS Imaging, Paris, France). SterEOS software was used for digital reconstruction. Femoral and tibial torsions were determined by analysing 3D reconstructions of each leg. Femoral torsion was defined as the angle between the femoral neck axis (FNA) and the posterior condylar axis (PCA). Tibial torsion was defined as the angle between the axis tangent to the posterior part of the tibia plateau and the transmalleolar axis. Arithmetic hip–knee–ankle angle (aHKA) and joint‐line obliquity (JLO) were also determined, allowing each leg to be assigned one of nine possible phenotypes according to CPAK.ResultsThe mean femoral torsion in CPAK type 1 was significantly higher (+ 2.6° ± 0.8°) than in CPAK type 4 (p = 0.02). All other CPAK types did not differ in the degree of femoral torsions. No differences could be demonstrated for the tibial torsion.ConclusionThere is a correlation between the coronal alignment of the lower limb and femoral torsion. This may provide the basis for extending the CPAK classification beyond the coronal plane.Level of EvidenceLevel III.
Neutral Block Copolymer Assisted Gene Delivery using Hydrodynamic Limb Vein Injection
Authors: Guen Yann Le , Delecourt Gwendoline , Gall Tony Le , Du Haiqin , Illy Nicolas , Huin Cécile , Bennevault Véronique , Midoux Patrick , Montier Tristan , Guégan Philippe 
Published: March 2024

AbstractThree different amphiphilic block copolymer families are synthesized to investigate new opportunities to enhance gene delivery via Hydrodynamic Limb Vein (HLV) injections. First a polyoxazoline‐based family containing mostly one poly(2‐methyl‐2‐oxazoline) (PMeOx) block and a second block POx with an ethyl (EtOx), isopropyl (iPrOx) or phenyl substituent (PhOx) is synthesized. Then an ABC poly(2‐ethyl‐2‐oxazoline)‐b‐poly(2‐n‐propyl‐2‐oxazoline)‐b‐poly(2‐methyl‐2‐oxazoline) triblock copolymer is synthesized, with a thermosensitive middle block. Finally, polyglycidol‐b‐polybutylenoxide‐b‐polyglycidol copolymers with various molar masses and amphiphilic balance are produced. The simple architecture of neutral amphiphilic triblock copolymer is not sufficient to obtain enhanced in vivo gene transfection. Double or triple amphiphilic neutral block copolymers are improving the in vivo transfection performances through HLV administration as far as a block having an lower critical solution temperature is incorporated in the vector. The molar mass of the copolymer does not seem to affect the vector performances in a significant manner.
Mucus‐Mimicking Mucin‐Based Hydrogels by Tandem Chemical and Physical Crosslinking
Authors: Porfiryeva Natalia N. , Zlotver Ivan , Davidovich‐Pinhas Maya , Sosnik Alejandro 
Published: March 2024

AbstractMucosal tissues represent a major interface between the body and the external environment and are covered by a highly hydrated mucins gel called mucus. Mucus lubricates, protects and modulates the moisture levels of the tissue and is capitalized in transmucosal drug delivery. Pharmaceutical researchers often use freshly excised animal mucosal membranes to assess mucoadhesion and muco‐penetration of pharmaceutical formulations which may struggle with limited accessibility, reproducibility, and ethical questions. Aiming to develop a platform for the rationale study of the interaction of drugs and delivery systems with mucosal tissues, in this work mucus‐mimicking mucin‐based hydrogels are synthesized by the tandem chemical and physical crosslinking of mucin aqueous solutions. Chemical crosslinking is achieved with glutaraldehyde (0.3% and 0.75% w/v), while physical crosslinking by one or two freeze‐thawing cycles. Hydrogels after one freeze‐thawing cycle show water content of 97.6–98.1%, density of 0.0529‐0.0648 g cm⁻3, and storage and loss moduli of ≈40–60 and ≈3–5 Pa, respectively, that resemble the properties of native gastrointestinal mucus. The mechanical stability of the hydrogels increases over the number of freeze‐thawing cycles. Overall results highlight the potential of this simple, reproducible, and scalable method to produce artificial mucus‐mimicking hydrogels for different applications in pharmaceutical research.
Preimplantation genetic testing as a means of preventing hereditary congenital myasthenic syndrome caused by RAPSN
Authors: Zhang Zhiping , Zhang Xueluo , Xue Huiqin , Chu Liming , Hu Lina , Bi Xingyu , Zhu Pengfei , Zhang Dongdong , Chen Jiayao , Cui Xiangrong , Kong Lingyin , Liang Bo , Wu Xueqing 
Published: March 2024

AbstractBackgroundCongenital myasthenic syndrome is a heterogeneous group of inherited neuromuscular transmission disorders. Variants in RAPSN are a common cause of CMS, accounting for approximately 14%–27% of all CMS cases. Whether preimplantation genetic testing for monogenic disease (PGT‐M) could be used to prevent the potential birth of CMS‐affected children is unclear.MethodsApplication of WES (whole‐exome sequencing) for carrier testing and guidance for the PGT‐M in the absence of a genetically characterized index patient as well as assisted reproductive technology were employed to prevent the occurrence of birth defects in subsequent pregnancy. The clinical phenotypes of stillborn fetuses were also assessed.ResultsThe family carried two likely pathogenic variants in RAPSN(NM_005055.5): c.133G>A (p.V45M) and c.280G>A (p.E94K). And the potential birth of CMS‐affected child was successfully prevented, allowing the family to have offspring devoid of disease‐associated variants and exhibiting a normal phenotype.ConclusionThis report constitutes the first documented case of achieving a CMS‐free offspring through PGT‐M in a CMS‐affected family. By broadening the known variant spectrum of RAPSN in the Chinese population, our findings underscore the feasibility and effectiveness of PGT‐M for preventing CMS, offering valuable insights for similarly affected families.
Chaotic‐quasi‐opposition based whale optimization technique applied to multi‐objective complementary scheduling of grid connected hydro‐thermal–wind–solar‐electric vehicle system
Authors: Paul Chandan , Roy Provas Kumar , Mukherjee V. 
Published: March 2024

AbstractThe sources of fossil fuel are impoverishing in upcoming future. In the current research scenario, sincere effort has been taken worldwide to explore the use of renewable energy sources in electrical power system for the economic benefits and environmental consciousness. The main contribution of the proposed work is first, to find optimal hydro‐thermal scheduling (HTS) with wind, solar, and electric vehicles (EVs) for variable load. The target is to find out maximum utilization of renewable energy sources for economic power generation with less emission. Thus, a new approach of EV to grid has been adopted with wind–solar based HTS system for improving grid reliability and resilience. Second, there is a requirement to overcome the local optima problems with less convergence speed. This is obtained by employing a relatively new methodology, known as chaotic‐quasi‐opposition‐based whale optimization algorithm (WOA) (CQOWOA). The proposed algorithm is tested on HTS and wind–solar‐electric vehicle‐based HTS (HTWSVS) for three different cases. Different nonlinearities like valve point effect of thermal units, transmission losses, spillage rate of hydro reservoir units and uncertainties of wind, solar as well as EV are considered to judge the effectiveness of the proposed CQOWOA technique on realistic problems. The presence of wind, solar, and EV energy sources with HTS is evident from the test results of CQOWOA, for multi‐objective problem where cost and emission both are reduced significantly. The robustness of the proposed solution has been verified by implementing the statistical analysis on two systems with least variation of mean and optimal values of cost with the tolerance of less than 0.025%. The comparative analysis of CQOWOA with the other optimization techniques validates its superiority on both the test systems by minimizing the generation cost and emission.
Laser Versus Cold Steel for Endoscopic Management of Subglottic Stenosis
Authors: Liang Kevin Y. , Miller Katherine M. , Syed Faez , Li Hong , Tierney William S. , Nelson Rebecca C. , Benninger Michael S. , Bryson Paul C. , Lorenz Robert R. 
Published: March 2024

AbstractObjectiveEndoscopic management of subglottic stenosis (SGS) includes a wide range of techniques. This 17‐year review compares treatment outcomes between carbon dioxide (CO2) laser and cold steel.Study DesignRetrospective chart review.SettingSingle tertiary care center.MethodsA chart review was performed for all patients undergoing endoscopic treatment of SGS at Cleveland Clinic between July 12, 2000 and September 1, 2017. Data collected included demographics, stenosis etiology, stenosis severity, comorbidities, treatment modality, and airway procedure history. The primary endpoint was repeated treatment‐free survival (RTFS) within 2 years using a Kaplan‐Meier analysis and Cox proportional hazard model.ResultsA total of 139 patients (median [interquartile range] aged 48.7 [37.8, 57.0] years; 83.4% female) were included in the analysis, with etiologies including idiopathic (56.8%), granulomatosis with polyangiitis (25.2%), and intubation (16.5%). All patients underwent either cold steel (107 patients) or CO2 laser (32 patients) lysis of stenosis with concurrent dilation. RTFS within 2 years was 50.2% for CO2 laser and 31.9% for cold steel (hazard ratio [HR] and 95% confidence interval [CI]: 1.69, 0.96‐2.97, P = .07). In patients with no prior airway procedures, there was no difference in RTFS between laser and cold knife (P = .41). However, in patients with prior airway procedures, RTFS was significantly greater in the laser group, even after adjusting for age, smoking history, and stenosis etiology (50.0% vs 16.8%, adjusted HR and CI: 2.82, 1.14‐6.98, P = .025).ConclusionEndoscopic lysis of SGS with CO2 laser should be considered in revision cases.
Beyond lecanemab: Examining Phase III potential in Alzheimer's therapeutics
Authors: Osaka Hitoshi , Nishida Keiichiro , Kanazawa Tetsufumi 
Published: March 2024

AbstractThis review focuses on the development of therapeutic interventions for Alzheimer's dementia. While established treatments targeted acetylcholine and NMDA receptors, there is a growing demand for innovative therapies as the aging population increases. The paper highlights the US Food and Drug Administration's approval of aducanumab (Aduhelm) and lecanemab (Leqembi), emphasizing the developmental status of new treatments. Specifically, it covers seven principal drugs in Phase III trials, detailing their mechanisms of action, clinical trial specifics in the United States and Japan, and the current status of regulatory applications. The review focuses on amyloid removal (donanemab), tau protein mitigation (E2814), drug repositioning (Semaglutide, GV1001), and disease‐modifying small molecules (fosgonimeton, hydralazine, masitinib). However, Gantenerumab and Solanezumab, unsuccessful in Phase III, are not covered. While the future approval status remains uncertain, we hope these drugs will offer beneficial therapeutic effects for potential dementia patients.
Synthesis of salcaprozate sodium and its significance in enhancing pancreatic kininogenase absorption performance
Authors: Lv Zhong , Luo Qian‐Dong , Tang Zhang‐Yong , Lv Xiao‐Hu , Wu Tao , Huang Ling‐Kai , Tang Can 
Published: March 2024

AbstractWe conducted pharmacokinetic research wherein salcaprozate sodium (SNAC) was utilized as a penetration enhancer by incorporating it into pancreatic kininogenase (PK) to improve the bioavailability of pancreatic kininogenase enteric‐coated tablets. We conducted in vitro studies on PK using the Caco‐2 cell model and quantified PK levels using the enzyme‐linked immunosorbent assay (ELISA) method. We conducted methodological verification by blending SNAC and PK powders into enteric‐coated capsules, and studied the pharmacokinetic characteristics. Based on the PK transport assay, the cumulative permeation rates of the test group that employed a SNAC to PK ratio of 32:1, 16:1, 8:1, 4:1, and 2:1 were 13.574%, 7.597%, 10.653%, 3.755%, and 2.523%, respectively. We conducted a uniformity test on the powder that contained a blend of SNAC and PK. The relative standard deviations (RSDs) for both the power containing SNAC and the power not containing SNAC were less than 10%. Based on the methodological verification, in vivo pharmacokinetic study of PK met the experimental requirements. As indicated by the results of in vivo pharmacokinetic research on rats, the test group (This group used SNAC) had a PK AUC0–12 h of 5679.747 ng/L*h and t1/2 of 4.569 h, while the control group (This group did not use SNAC) had a PK AUC0–12 h of 4639.665 ng/L*h and t1/2 of 3.13 h. This study has established a low‐cost, environmentally friendly, and safe SNAC synthesis route with high process yield suitable for industrial production. SNAC demonstrates an absorption‐enhancing effect on PK, and the optimal ratio of SNAC to PK is determined to be 32:1.
Pectin From Fruit Peel Waste: A Sustainable Source for Production of Active Packaging Films
Authors: Kanatt Sweetie R. 
Published: March 2024

ABSTRACTPectin from lemon and passion fruit peels was studied for its potential to serve as a source of biopolymer for preparation of active film. To develop a packaging film appropriate for fruits, different combinations of polyvinyl alcohol (PVA), pectin from lemon and passion fruit peel and rosemary essential oil (REO) were evaluated. Extensive characterisation of these films with respect to colour, thickness, moisture, opacity, UV absorption, tensile strength, elongation, swelling, solubility and thermal and chemical interactions was studied. Film prepared with PVA, lime and pectin peel (2:1:1 v/v) without REO and glycerol as plasticiser was found to be best based on the above properties. Additionally, the effectiveness of this film at extending the shelf life of strawberries and plums was evaluated. Physiological changes on storage were lesser in active packaged fruits as compared to unpackaged fruits. On basis of several spoilage indices studied, unpacked fruits had shelf life of less than 7 days, while those packed in active film were acceptable up to 15 days in case of strawberry and 45 in case of plums when stored at chilled temperature (6°C). Thus, use of the developed active packaging film would be beneficial for extending the marketable period of the fruits and enhancing its cost‐effectiveness.