bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Sirolimus treatment on patients with β‐Thalassemia: Lymphocyte immunophenotype and biological activity of memory CD4+ and CD8+ T cells
Authors: Zurlo Matteo , Nicoli Francesco , Proietto Davide , Dallan Beatrice , Zuccato Cristina , Cosenza Lucia Carmela , Gasparello Jessica , Papi Chiara , d'Aversa Elisabetta , Borgatti Monica , Scapoli Chiara , Finotti Alessia , Gambari Roberto 
Published: January 2023

AbstractInhibitors of the mammalian target of rapamycin (mTOR) have been proposed to improve vaccine responses, especially in the elderly. Accordingly, testing mTOR inhibitors (such as Sirolimus) and other geroprotective drugs might be considered a key strategy to improve overall health resilience of aged populations. In this respect, Sirolimus (also known as rapamycin) is of great interest, in consideration of the fact that it is extensively used in routine therapy and in clinical studies for the treatment of several diseases. Recently, Sirolimus has been considered in laboratory and clinical studies aimed to find novel protocols for the therapy of hemoglobinopathies (e.g. β‐Thalassemia). The objective of the present study was to analyse the activity of CD4+ and CD8+ T cells in β‐Thalassemia patients treated with Sirolimus, taking advantages from the availability of cellular samples of the NCT03877809 clinical trial. The approach was to verify IFN‐γ releases following stimulation of peripheral blood mononuclear cells (PBMCs) to stimulatory CEF and CEFTA peptide pools, stimulatory for CD4+ and CD8+ T cells, respectively. The main results of the present study are that treatment of β‐Thalassemia patients with Sirolimus has a positive impact on the biological activity and number of memory CD4+ and CD8+ T cells releasing IFN‐γ following stimulation with antigenic stimuli present in immunological memory. These data are to our knowledge novel and in our opinion of interest, in consideration of the fact that β‐Thalassemia patients are considered prone to immune deficiency.
Simple cost‐effective larval injection method for dsRNA delivery to induce RNAi response in Helicoverpa armigera (Hübner)
Authors: Das Joy , Kumar Rakesh , Shah Vivek , Sharma Ashwani Kumar 
Published: January 2023

AbstractMicroinjection is considered as an effective method for dsRNA delivery in insects. It also facilitates the delivery of a precise quantity of dsRNA in the host insect, inducing an efficient RNAi response. However, the microinjection method needs prior optimization of several parameters like concentration of dsRNA, site of injection, developmental stage of insect etc. for inducing effective RNAi response. Moreover, sophisticated microinjection devices are largely expensive with high maintenance cost. The Old‐World bollworm, Helicoverpa armigera (Hübner) is known to be a detrimental polyphagous pest with widespread infestations across the globe. In the present study, we demonstrate a low‐cost and effective dsRNA delivery method for inducing RNAi response in H. armigera with the aid of basic insulin injection syringe and fabricated micropipette tip. In order to validate the RNAi response following dsRNA injection, we have selected three key genes from the chitin biosynthesis pathway of the insect. Besides these, argonaute 1 (ago1) was also used as an indicator gene for dsRNA‐mediated RNAi induction. Delivery of dsRNA using injection with insulin syringe caused significant upregulation of the ago1 gene in the insect irrespective of any of the three target genes concerned viz. HaNAGK (3.9 fold; p < 0.001), HaAGM (6.3 fold; p < 0.001) and HaUAP (5.9 fold; p < 0.01) respectively, as compared to control injected with nuclease‐free water. The dsRNA‐injected insects showed aberrant developmental symptoms typical of impeded chitin synthesis, eventually leading to anomalous ecdysis with substantial mortality (up to 69.04%), as compared to controls. The described protocol reduces insect injury, enabling easy restraining of larva and quick execution of dsRNA injection with efficient RNAi response.
Genomic vulnerability to climate change in Quercus acutissima, a dominant tree species in East Asian deciduous forests
Authors: Yuan Shuai , Shi Yong , Zhou Biao‐Feng , Liang Yi‐Ye , Chen Xue‐Yan , An Qing‐Qing , Fan Yan‐Ru , Shen Zhao , Ingvarsson Pär K. , Wang Baosheng 
Published: January 2023

AbstractUnderstanding the evolutionary processes that shape the landscape of genetic variation and influence the response of species to future climate change is critical for biodiversity conservation. Here, we sampled 27 populations across the distribution range of a dominant forest tree, Quercus acutissima, in East Asia, and applied genome‐wide analyses to track the evolutionary history and predict the fate of populations under future climate. We found two genetic groups (East and West) in Q. acutissima that diverged during Pliocene. We also found a heterogeneous landscape of genomic variation in this species, which may have been shaped by population demography and linked selections. Using genotype‐environment association analyses, we identified climate‐associated SNPs in a diverse set of genes and functional categories, indicating a model of polygenic adaptation in Q. acutissima. We further estimated three genetic offset metrics to quantify genomic vulnerability of this species to climate change due to the complex interplay between local adaptation and migration. We found that marginal populations are under higher risk of local extinction because of future climate change, and may not be able to track suitable habitats to maintain the gene–environment relationships observed under the current climate. We also detected higher reverse genetic offsets in northern China, indicating that genetic variation currently present in the whole range of Q. acutissima may not adapt to future climate conditions in this area. Overall, this study illustrates how evolutionary processes have shaped the landscape of genomic variation, and provides a comprehensive genome‐wide view of climate maladaptation in Q. acutissima.
Commonly used dental mouthwashes and SARS‐CoV‐2—The road to what we know today
Authors: Vigen Ellen C. , Skoglund Maria K. 
Published: January 2023

AbstractThe aim of this brief overview is to give clinicians a background for assessing publications presenting in vivo human clinical trials regarding the effect of common dental mouthwashes on SARS‐CoV‐2 virus. It explains how the effects of oral mouthwashes on oro‐nasally transmitted infectious virus was assessed in the early phase of the Covid‐19 pandemic. The method of virus quantification including effect measures and factors, trial design that may cause flaws in the effect estimates presented in publications are explained. The status of in vivo human clinical trials regarding the anti‐virucidal effect of sodium lauryl sulfate, povidone‐iodine, chlorhexidine, hydrogen peroxide and cetylpyridinium chloride is presented from the few systematic reviews available at this time.
Dissecting succulence: Crassulacean acid metabolism and hydraulic capacitance are independent adaptations in Clusia leaves
Authors: Leverett Alistair , Hartzell Samantha , Winter Klaus , Garcia Milton , Aranda Jorge , Virgo Aurelio , Smith Abigail , Focht Paulina , Rasmussen‐Arda Adam , Willats William G. T. , Cowan‐Turner Daniel , Borland Anne M. 
Published: January 2023

AbstractSucculence is found across the world as an adaptation to water‐limited niches. The fleshy organs of succulent plants develop via enlarged photosynthetic chlorenchyma and/or achlorophyllous water storage hydrenchyma cells. The precise mechanism by which anatomical traits contribute to drought tolerance is unclear, as the effect of succulence is multifaceted. Large cells are believed to provide space for nocturnal storage of malic acid fixed by crassulacean acid metabolism (CAM), whilst also buffering water potentials by elevating hydraulic capacitance (CFT). The effect of CAM and elevated CFT on growth and water conservation have not been compared, despite the assumption that these adaptations often occur together. We assessed the relationship between succulent anatomical adaptations, CAM, and CFT, across the genus Clusia. We also simulated the effects of CAM and CFT on growth and water conservation during drought using the Photo3 model. Within Clusia leaves, CAM and CFT are independent traits: CAM requires large palisade chlorenchyma cells, whereas hydrenchyma tissue governs interspecific differences in CFT. In addition, our model suggests that CAM supersedes CFT as a means to maximise CO2 assimilation and minimise transpiration during drought. Our study challenges the assumption that CAM and CFT are mutually dependent traits within succulent leaves.
Acral collodion membrane associated with ichthyosis due to a heterozygous pathogenic variant of ELOVL4 gene
Authors: Monir Reesa L. , Schoch Jennifer J. 
Published: January 2023

AbstractA female twin presented at birth with a collodion membrane on the hands and feet. After the membrane resolved over the first months of life, she was initially diagnosed with acral self‐healing collodion membrane. However, she subsequently developed brown well‐defined geometric scales on the trunk and extremities, consistent with ichthyosis. Genetic testing showed a heterozygous pathogenic variant in ELOVL4, a gene associated with syndromic ichthyosis with developmental delay, seizures, and spasticity. Although acral collodion membrane is considered to be a benign variant of the more generalized collodion, usually described as “self‐healing,” it may be the initial presentation of more diffuse ichthyosis.
U-Pb zircon ages from metasedimentary and plutonic rocks in the Bras d'Or terrane of Cape Breton Island, Nova Scotia, Canada: insights into the Ediacaran–Cambrian tectonomagmatic evolution of Ganderia
Authors: van Rooyen Deanne , Barr Sandra M. , White Chris E. , Crowley James L. 
Published: January 2023

The Bras d'Or terrane of central Cape Breton Island, Nova Scotia, Canada, contains a well-preserved record of the Ediacaran to early Cambrian evolution of Ganderia, a Gondwana-derived terrane in the northern Appalachian orogen. A complex assemblage of low- to high-grade metasedimentary rocks has varied detrital zircon signatures from laser ablation inductively coupled plasma mass spectrometry U-Pb zircon dating, but combining three or more samples yielded representative age spectra that support correlation of the low- and high-grade metasedimentary rocks throughout the Bras d'Or terrane and the corresponding Ganderian Brookville terrane of southern New Brunswick. In quartzite samples from the McMillan Flowage Formation in the northwestern Bras d'Or terrane, the youngest detrital zircons have ages >900 Ma, in contrast to previously studied psammitic and semipelitic samples from correlative units in the eastern Bras d'Or terrane in which youngest detrital ages are 620–600 Ma. Both quartzite and semipelitic samples from the McMillan Flowage Formation contain Neoproterozoic dates from zircon rims, which reflect metamorphic overgrowths during peak metamorphism at ca. 550 Ma, providing a robust age for peak metamorphism in the Bras d'Or terrane that supports similar, albeit sparse, ages reported previously from monazite and titanite samples. This metamorphism is coeval with the emplacement of voluminous dioritic to granitic plutons that occur throughout the Bras d'Or terrane and form in an Andean-type continental margin subduction zone. New U-Pb zircon ages presented here from plutons in the northern Bras d'Or terrane, combined with previously published ages, are consistent with subduction-related magmatism and associated metamorphism between ca. 575 and 540 Ma.
Platelet-Mimicking Nanosponges for Functional Reversal of Antiplatelet Agents
Authors: Xu Junchao , Yan Na , Wang Chunling , Gao Chao , Han Xuexiang , Yang Chengzhi , Xu Jiaqi , Wang Kun , Mitchell Michael J. , Zhang Yinlong , Nie Guangjun 
Published: January 2023

Background:
During long-term antiplatelet agents (APAs) administration, patients with thrombotic diseases take a fairly high risk of life-threatening bleeding, especially when in need of urgent surgery. Rapid functional reversal of APAs remains an issue yet to be efficiently resolved by far due to the lack of any specific reversal agent in the clinic, which greatly restricts the use of APAs.

Methods:
Flow cytometry analysis was first applied to assess the dose-dependent reversal activity of platelet-mimicking perfluorocarbon-based nanosponges (PLT-PFCs) toward ticagrelor. The tail bleeding time of mice treated with APAs followed by PLT-PFCs was recorded at different time points, along with corresponding pharmacokinetic analysis of ticagrelor and tirofiban. A hemorrhagic transformation model was established in experimental stroke mice with thrombolytic/antiplatelet therapy. Magnetic resonance imaging was subsequently applied to observe hemorrhage and thrombosis in vivo. Further evaluation of the spontaneous clot formation activity of PLT-PFCs was achieved by clot retraction assay in vitro.

Results:
PLT-PFCs potently reversed the antiplatelet effect of APAs by competitively binding with APAs. PLT-PFCs showed high binding affinity comparable to fresh platelets in vitro with first-line APAs, ticagrelor and tirofiban, and efficiently reversed their function in both tail bleeding and postischemic-reperfusion models. Moreover, the deficiency of platelet intrinsic thrombotic activity diminished the risk of thrombogenesis.

Conclusions:
This study demonstrated the safety and effectiveness of platelet-mimicking nanosponges in ameliorating the bleeding risk of different APAs, which offers a promising strategy for the management of bleeding complications induced by antiplatelet therapy.
Social Determinants of Cardiovascular Health: A Longitudinal Analysis of Cardiovascular Disease Mortality in US Counties From 2009 to 2018
Authors: Son Heejung , Zhang Donglan , Shen Ye , Jaysing Anna , Zhang Jielu , Chen Zhuo , Mu Lan , Liu Junxiu , Rajbhandari‐Thapa Janani , Li Yan , Pagán José A. 
Published: January 2023

Background
Disparities in cardiovascular disease (CVD) outcomes persist across the United States. Social determinants of health play an important role in driving these disparities. The current study aims to identify the most important social determinants associated with CVD mortality over time in US counties.

Methods and Results
The authors used the Agency for Healthcare Research and Quality's database on social determinants of health and linked it with CVD mortality data at the county level from 2009 to 2018. The age‐standardized CVD mortality rate was measured as the number of deaths per 100 000 people. Penalized generalized estimating equations were used to select social determinants associated with county‐level CVD mortality. The analytic sample included 3142 counties. The penalized generalized estimating equation identified 17 key social determinants of health including rural–urban status, county's racial composition, income, food, and housing status. Over the 10‐year period, CVD mortality declined at an annual rate of 1.08 (95% CI, 0.74–1.42) deaths per 100 000 people. Rural counties and counties with a higher percentage of Black residents had a consistently higher CVD mortality rate than urban counties and counties with a lower percentage of Black residents. The rural–urban CVD mortality gap did not change significantly over the past decade, whereas the association between the percentage of Black residents and CVD mortality showed a significant diminishing trend over time.

Conclusions
County‐level CVD mortality declined from 2009 through 2018. However, rural counties and counties with a higher percentage of Black residents continued to experience higher CVD mortality. Median income, food, and housing status consistently predicted higher CVD mortality.
Transcarpal Motor Conduction Velocity: Repeatability and Application in Carpal Tunnel Syndrome
Authors: Das Pinaki , Ghosh Parasar , Halder Subhankar , Kumar Subhankar 
Published: January 2023

Background Conduction velocity of the short segment of the median motor nerve, across wrist (transcarpal motor conduction velocity (TCMCV)), has been used to increase diagnostic yield in carpal tunnel syndrome (CTS). However, repeatability of this parameter has not been studied till date. It has not been used as an indicator of response to treatment. Using surface stimulation techniques, it is difficult to localize the sites of stimulation of transcarpal segment of median nerve in palm. As a result, small errors in measurements of TCMCV can be magnified and variability of TCMCV may occur on successive measurements. Despite this possible variation, TCMCV can be a useful tool for assessing response to therapy, if its repeatability is assessed and a cut-off value determined for a significant change in nerve conduction velocity. Purpose In this study, it was determined whether TCMCV is repeatable. If found to be repeatable, we show a method to determine the cut-off value of the change in this parameter for it to be considered significant. Methods Difference between values of TCMCV on successive measurements was obtained in hands of 26 controls. Repeatability of this parameter was determined in this control population following criteria of British Standards Institution. In 19 patients of CTS, treated with intracarpal steroid injection, pre-treatment and post-treatment values of TCMCV, and of symptom severity scale (SSS) and functional status scale (FSS), were obtained at 1, 2, and 3 months after treatment. Results Repeat measurements of TCMCV were made in each hand of all controls. After applying criteria of British Standards Institution, to such recordings, TCMCV was found to be repeatable and the cut-off value for significant change determined. According to this cut-off value, 4 patients of CTS showed improvement in TCMCV, with consistent improvement in SSS and FSS. Change in TCMCV corroborated qualitatively with changes in SSS and FSS. Conclusion Repeatability of TCMCV can be assessed by criteria of British Standards Institution and a cut-off value determined to use it as an indicator of response to treatment in CTS.
Computed tomography improves the diagnostic accuracy but not the interobserver reliability of the Boileau classification of proximal humerus fracture sequelae
Authors: Cozzolino Andrea , Malfi Paolofrancesco , de Giovanni Roberto , Fedele Alfonso , Rusconi Giovanni , Guarino Amedeo , Di Pietto Francesco , Russo Raffaele 
Published: January 2023

Background The aim of this study was to investigate the impact of computed tomography on the reliability of Boileau classification for proximal humerus fracture sequelae. Methods A prospective study was designed using STARD guidelines. We included all patients diagnosed with proximal humerus fracture sequelae who underwent surgery at our institution between 2017 and 2021. Preoperative radiographs and computed tomography scans were reviewed by three independent observers. Intra- and inter-observer reliability and the diagnostic accuracy of radiographs and computed tomography scans in detecting chronic dislocation, nonunion, and severe greater tuberosity dislocation were assessed. Results Fifty-two patients were included in the study. The overall interobserver agreement was low on both radiographs and computed tomography scans. On radiographic images, we found a sensitivity of 97%, 88.9%, and 84.1%, and a specificity of 58.3%, 40%, and 53.3% to detect chronic dislocation, nonunion, and greater tuberosity dislocation, respectively. On computed tomography scans we reported a sensitivity of 100%, 96.8%, and 93.7%, and a specificity of 91.7%, 86.7%, and 93.3% to detect chronic dislocation, nonunion, and greater tuberosity dislocation, respectively. Discussion Computed tomography scan was more specific than radiographs in the assessment of proximal humerus fracture sequelae. However, even using a three-dimensional evaluation of the deformity, the Boileau classification had a poor interobserver reliability. Level of Evidence I. Testing previously developed diagnostic criteria in a consecutive series of patients and a universally applied “gold standard.”
A Patient-Reported Outcome-Based Comparison of Cheilectomy With and Without Proximal Phalangeal Dorsiflexion Osteotomy for Hallux Rigidus
Authors: Kim Jaeyoung , Rajan Lavan , Fuller Robert M. , Mizher Rami , Cororaton Agnes D. , Kumar Prashanth , An Tonya W. , Deland Jonathan T. , Ellis Scott J. 
Published: January 2023

Introduction This study provides the first comparison of patient-reported outcomes between isolated cheilectomy (C) and cheilectomy with Moberg (CM) osteotomy for hallux rigidus. Methods A single-center, retrospective registry search identified all patients with preoperative Patient-Reported Outcomes Measurement Information System (PROMIS) scores who underwent cheilectomy, with and without concomitant proximal phalangeal dorsiflexion osteotomy, for hallux rigidus between January 2016 and December 2020. Because there were far fewer isolated cheilectomies (62), all C patients were compared with a commensurate number of consecutive CM cases (67) using preoperative, 1-year, and 2-year PROMIS scores for physical function, pain interference, pain intensity, global physical health, global mental health, and depression, as well as complication and revision data from a chart review. A multivariable linear regression analysis was performed to compare adjusted postoperative PROMIS scores between the 2 cohorts. Results There were no differences between groups among the demographic and preoperative variables compared. The CM cohort reported worse pain interference scores preoperatively (P < .001) and at 1 year postoperatively (P = .01). However, the C cohort reported worse pain intensity scores preoperatively (P < .001) and at 1 year postoperatively (P < .001). Adjusted postoperative PROMIS score comparison demonstrated that the CM cohort had better 1-year postoperative pain intensity scores (P < .05). However, there were no differences between cohorts for additional PROMIS scores or complications data. Conclusion The addition of a Moberg osteotomy does not appear to significantly change short- to medium-term outcomes of cheilectomy for hallux rigidus treatment. Levels of Evidence: Level III: Retrospective comparative study