bluuebunny/crossref_metadata_2025_split huggingface dataset:
A unique case of anaplastic thyroid carcinoma comprising of two distinct patterns osteoclastic variant and squamous cell carcinoma in separate lobe imitating collision tumor: A case report
Authors: Gupta Rakesh Kumar , John Aishwarya , Ravina Mudalsha , Arora Ripu Daman 
Published: December 2022

AbstractAnaplastic thyroid carcinoma with two distinct morphologies in two lobes with no intermixing is very rare and not reported earlier. Furthermore, osteoclastic variant of anaplastic thyroid carcinoma as well as primary squamous cell carcinoma without any differentiated components are also very rare with only few reported cases describing their cytological features. Herein, we are reporting a unique and first case of anaplastic thyroid carcinoma comprising of two distinct patterns osteoclastic variant and squamous cell carcinoma in different lobes in a 55‐years‐old lady with review of literature.
Deep marine diagenesis, offshore Hawaii and Enewetak, with implications for older carbonates
Authors: Saller Arthur , Winterbottom Charlotte 
Published: December 2022

AbstractCenozoic limestones from Hawaii and Enewetak were studied to characterise diagenesis in deep sea water. Hawaii samples were from subsea outcrops of drowned Pleistocene reefs 150–1,505 m deep (maximum age 550–600 ka). Most samples had early fibrous aragonite and high‐magnesium calcite cements precipitated in shallow sea water. Partial dissolution of aragonite (including coral) and high‐magnesium calcite were significant at 412 m and increased to 1,505 m. Crusts of ‘stubby’ sparry calcite cement (2–8 mol.% MgCO3; ‘lower Mg calcite’) precipitated on early aragonite and high‐magnesium calcite cements at 473–1,358 m. Dissolution of aragonite and high‐magnesium calcite was incomplete. Aragonite and high‐magnesium calcite were not neomorphosed to low‐magnesium calcite ( <5 mol.% MgCO3). Enewetak well samples came from 3 to 1,400 m (Holocene to Upper Eocene). Lower Miocene to Upper Eocene carbonates at 380–1,380 m near the atoll margin showed pervasive dissolution of aragonite and conversion of high‐magnesium calcite fossils to low‐magnesium calcite. Their lower‐Mg calcite cements (380–820 m; mainly radiaxial) were associated with aragonite dissolution. The lower‐Mg calcite cements and bulk limestones below 500 m had geochemistry indicating precipitation or stabilisation in sea water at 10–27°C. Data indicate Enewetak dolomitisation (1,250–1,320 m) in cold sea water during burial >1,000 m. Coralline algae showed little petrographic alteration, but Mg decreased downward from 15 to 1.5 mol.% MgCO3. In both areas, aragonite dissolution, alteration of high‐magnesium calcite, and precipitation of lower‐Mg calcite cements occurred in deep sea water (>300 m) undersaturated for aragonite, but supersaturated for low‐magnesium calcite. Original high‐magnesium calcite was partially dissolved in Hawaii samples, but converted to low‐magnesium calcite in deep Enewetak cores, possibly due to gradual deepening at Enewetak. Dolomitisation and low‐magnesium calcite dissolution occurred below the calcite saturation depth (approximately 1,000 m) in Enewetak, but not deep Hawaii samples, possibly because dolomitisation is slower. Temporal variations in carbonate saturation, especially related to pCO2, are interpreted as the main control on mineralogy during marine diagenesis now and in many ancient oceans.
Phenological response to climate variation in a northern red oak plantation: Links to survival and productivity
Authors: Knott Jonathan A. , Liang Liang , Dukes Jeffrey S. , Swihart Robert K. , Fei Songlin 
Published: December 2022

AbstractIn a changing climate, the future survival and productivity of species rely on individual populations to respond to shifting environmental conditions. Many tree species, including northern red oak (Quercus rubra), exhibit phenotypic plasticity, the ability to respond to changes in environmental conditions at within‐generation time scales, through varying traits such as leaf phenology. Phenotypic plasticity of phenology may vary among populations within a species' range, and it is unclear if the range of plasticity is adequate to promote fitness. Here, we used a 58‐year‐old common garden to test whether northern red oak populations differed in phenological sensitivity to changes in temperature and whether differences in phenological sensitivity were associated with differences in productivity and survival (proxies of fitness). We recorded 8 years of spring leaf emergence and autumn leaf coloration and loss in 28 distinct populations from across the species' full range. Across the 28 populations, spring leaf out consistently advanced in warmer years, but fall phenology was less responsive to changes in temperature. Southern, warm‐adapted populations had larger shifts in phenology in response to springtime warming but had lower long‐term survival. Moreover, higher phenological sensitivity to spring warming was not strongly linked to increased productivity. Instead, fitness was more closely linked to latitudinal gradients. Although springtime phenological sensitivity to climate change is common across northern red oak populations, responses of productivity and survival, which could determine longer‐term trajectories of species abundance, are more variable across the species' range.
Single‐cell fate mapping reveals widespread clonal ignorance of low‐affinity T cells exposed to systemic infection
Authors: Leube Justin , Mühlbauer Anton , Andrä Immanuel , Biggel Madleen , Busch Dirk H. , Kretschmer Lorenz , Buchholz Veit R. 
Published: December 2022

AbstractT cell ignorance is a specific form of immunological tolerance. It describes the maintenance of naivety in antigen‐specific T cells in vivo despite the presence of their target antigen. It is thought to mainly play a role during the steady state, when self‐antigens are presented in absence of costimulatory signals and at low density or to T cells of low affinity. In how far antigen‐specific T cells can also remain clonally ignorant to foreign antigens, presented in the inflammatory context of systemic infection, remains unclear. Using single‐cell in vivo fate mapping and high throughput flow cytometric enrichment, we find that high‐affinity antigen‐specific CD8+ T cells are efficiently recruited upon systemic infection. In contrast, most low‐affinity antigen‐specific T cells ignore the priming antigen and persist in the naïve state while remaining fully responsive to subsequent immunization with a high‐affinity ligand. These data establish the widespread clonal ignorance of low‐affinity T cells as a major factor shaping the composition of antigen‐specific CD8+ T cell responses to systemic infection.
Quality evaluation of immunomodulatory polysaccharides from Agaricus bisporus by an integrated fingerprint technique
Authors: Yuan Qin , Liu Wen , Huang Ling , Wang Liju , Yu Juan , Wang Yitao , Wu Ding‐Tao , Wang Shengpeng 
Published: December 2022

AbstractAgaricus bisporus (A. bisporus) is a rich source of polysaccharides with medical and nutraceutical interests; however, the complex structure of A. bisporus polysaccharides (ABPs) poses a challenge to its quality control. This study aims to investigate the immunomodulatory fractions of ABPs and further establish a quality control system for the detection and characterization of bioactive ABPs. Two fractions of ABPs were obtained using gradient alcohol precipitation combined ultrafiltration, followed by characterization of molecular weight, monosaccharide composition, chemical structure, and evaluation of immunomodulatory activity. Results showed that the two isolated fractions with different molecular weight, 8.95 × 106 Da (ABP17‐1) and 1.73 × 104 Da (ABP17‐2), were more homogeneous and exerted stronger immunomodulatory activity than that of ABPs. Furthermore, an integrated fingerprint technique including HPSEC‐MALL‐RID and HPLC was applied for the fingerprint analysis of ABPs from 17 batches of A. bisporus, which showed high similarity. Besides, two polysaccharide fractions, two monosaccharides (glucose and galactose), and the main cellulose hydrolysate glucose were identified as potential quality control markers of ABPs. Overall, this study could help better understand the structure–activity relationship of ABPs and serve as a guidance for the quality control of active ABPs and their related products.
A pilot randomized sham controlled trial of bilateral iTBS for depression and executive function in older adults
Authors: Cristancho Pilar , Arora Jyoti , Nishino Tomoyuki , Berger Jacinda , Carter Alexandre , Blumberger Daniel , Miller Philip , Snyder Abraham , Barch Deanna , Lenze Eric J. 
Published: December 2022

AbstractIntroductionExecutive function deficits (EFD) in late life depression (LLD) are associated with poor outcomes. Dysfunction of the cognitive control network (CCN) has been posited in the pathophysiology of LLD with EFD.MethodsSeventeen older adults with depression and EFD were randomized to iTBS or sham for 6 weeks. Intervention was delivered bilaterally using a recognized connectivity target.ResultsA total of 89% (17/19) participants completed all study procedures. No serious adverse events occurred. Pre to post‐intervention change in mean Montgomery‐Asberg‐depression scores was not different between iTBS or sham, p = 0.33. No significant group‐by‐time interaction for Montgomery‐Asberg Depression rating scale scores (F
3, 44 = 0.51; p = 0.67) was found. No significant differences were seen in the effects of time between the two groups on executive measures: Flanker scores (F
1, 14 = 0.02, p = 0.88), Dimensional‐change‐card‐sort scores F
1, 14 = 0.25, p = 0.63, and working memory scores (F
1, 14 = 0.98, p = 0.34). The Group‐by‐time interaction effect for functional connectivity (FC) within the Fronto‐parietal‐network was not significant (F
1, 14 = 0.36, p = 0.56). No significant difference in the effect‐of‐time between the two groups was found on FC within the Cingulo‐opercular‐network (F
1, 14 = 0, p = 0.98).ConclusionBilateral iTBS is feasible in LLD. Preliminary results are unsupportive of efficacy on depression, executive function or target engagement of the CCN. A future Randomized clinical trial requires a larger sample size with stratification of cognitive and executive variables and refinement in the target engagement.
System and policy‐level barriers and facilitators for timely and accurate diagnosis of young onset dementia
Authors: Burkinshaw Kirsty , Tsourtos George , Cations Monica 
Published: December 2022

AbstractObjectiveThe multiyear diagnostic journey for young onset dementia (YOD) is fraught with clinical and personal difficulties and poses significant uncertainty for people living with YOD and their families. Most existing research has examined the personal and/or clinical barriers to a timely diagnosis of YOD, but less evidence exists regarding system level factors. The aim of this study is to investigate health professionals' insights for a timely and accurate YOD diagnosis at the system level.DesignGrounded theory qualitative study.Setting and ParticipantsSemi‐structured in‐depth interviews with 11 health professionals working across varied healthcare settings were conducted online via videoconference.MeasurementsData were contrasted and compared within and between transcripts using the constant comparative method.ResultsSeven themes emerged about barriers and facilitators for timely and accurate diagnosis of YOD: (1) stigma and awareness of YOD; (2) mismatched policy; (3) fractured health system; (4) inadequate pathways for YOD diagnostic care; (5) effective use of General Practitioners; (6) inequitable access and fragmented service navigation; (7) diverse and marginalised groups.ConclusionA complex web of systemic and system level barriers contributes to the delay of accurate and timely diagnosis for YOD. Diverse and marginalised groups experience greater inequitable disadvantage regarding YOD diagnostic care. There is an urgent need to focus on YOD diagnosis facilitators at the broader health system level.
Brain functional connectivity alterations associated with neuropsychological performance 6–9 months following SARS‐CoV‐2 infection
Authors: Voruz Philippe , Cionca Alexandre , Jacot de Alcântara Isabele , Nuber‐Champier Anthony , Allali Gilles , Benzakour Lamyae , Lalive Patrice H. , Lövblad Karl O. , Braillard Olivia , Nehme Mayssam , Coen Matteo , Serratrice Jacques , Reny Jean‐Luc , Pugin Jérôme , Guessous Idris , Ptak Radek , Landis Basile N. , Adler Dan , Griffa Alessandra , Van De Ville Dimitri , Assal Frédéric , Péron Julie A. 
Published: December 2022

AbstractNeuropsychological deficits and brain damage following SARS‐CoV‐2 infection are not well understood. Then, 116 patients, with either severe, moderate, or mild disease in the acute phase underwent neuropsychological and olfactory tests, as well as completed psychiatric and respiratory questionnaires at 223 ± 42 days postinfection. Additionally, a subgroup of 50 patients underwent functional magnetic resonance imaging. Patients in the severe group displayed poorer verbal episodic memory performances, and moderate patients had reduced mental flexibility. Neuroimaging revealed patterns of hypofunctional and hyperfunctional connectivities in severe patients, while only hyperconnectivity patterns were observed for moderate. The default mode, somatosensory, dorsal attention, subcortical, and cerebellar networks were implicated. Partial least squares correlations analysis confirmed specific association between memory, executive functions performances and brain functional connectivity. The severity of the infection in the acute phase is a predictor of neuropsychological performance 6–9 months following SARS‐CoV‐2 infection. SARS‐CoV‐2 infection causes long‐term memory and executive dysfunctions, related to large‐scale functional brain connectivity alterations.
Recent advances in the diagnosis and management of typhoid fever in Africa: A review
Authors: Mahmoud Ashraf , Oluyemisi Adekunbi , Uwishema Olivier , Sun Jeffrey , Jobran Afnan Waleed , David Success , Wireko Andrew Awuah , Adanur Irem , Dost Burhan , Onyeaka Helen 
Published: December 2022

AbstractTyphoid fever, a classical disease of enteric origin caused by Salmonella species of bacteria, is among the most important diseases threatening public health in Africa. The African continent is a marker for both low resources within the healthcare system and poor disease control policy formulations in managing endemic infectious diseases. Since the colonial era, the Widal serological test has been used to confirm typhoid fever in Africa, however recent studies recommend blood culture, and when blood culture cannot be obtained, clinical findings, laboratory Widal test confirmation, and ruling out other febrile illnesses as confirmatory pathway to diagnose typhoid fever in Africa. Managing typhoid fever relies on antimicrobials. In 1980s chloramphenicol was the medication of choice. Years later, amoxicillin and co‐trimoxazole were adopted. However, the instantaneous rise of resistant strains of Salmonella enterica confers an important challenge to treat the burdensome enteric fever. The current treatment algorithm of typhoid fever in Africa relies significantly on the use of fluoroquinolones, macrolides, and cephalosporins. Developed nations have successfully addressed and controlled typhoid fever via improvement in accessing safe water and food, better sanitary and hygienic behaviours, and vaccines development. Nevertheless, there is significant evidence to infer improvement in the diagnosis management of typhoid fever over the last few decades, and efforts are underway to control the disease spread in Africa. This review aims to provide an overview of the latest developments in typhoid fever diagnosis and management in Africa and provide key recommendations for a coordinated approach to mitigate typhoid in the continent.
Gene Therapy Using Recombinant AAV Type 8 Vector Encoding TNAP‐D10 Improves the Skeletal Phenotypes in Murine Models of Osteomalacia
Authors: Amadeu de Oliveira Flavia , Mohamed Fatma F. , Kinoshita Yuka , Narisawa Sonoko , Farquharson Colin , Miyake Koichi , Foster Brian L , Millan Jose Luis 
Published: December 2022

ABSTRACTHypophosphatasia (HPP), caused by loss‐of‐function mutations in the ALPL gene encoding tissue‐nonspecific alkaline phosphatase (TNAP), is characterized by skeletal and dental hypomineralization that can vary in severity from life‐threatening to milder manifestations only in adulthood. PHOSPHO1 deficiency leads to early‐onset scoliosis, osteomalacia, and fractures that mimic pseudo‐HPP. Asfotase alfa, a life‐saving enzyme replacement therapy approved for pediatric‐onset HPP, requires subcutaneous injections 3 to 6 times per week. We recently showed that a single injection of an adeno‐associated virus vector serotype 8 harboring TNAP‐D10 (AAV8‐TNAP‐D10) effectively prevented skeletal disease and prolonged life in Alpl−/− mice phenocopying infantile HPP. Here, we aimed to determine the efficacy of AAV8‐TNAP‐D10 in improving the skeletal and dental phenotype in the AlplPrx1/Prx1 and Phospho1−/− mouse models of late‐onset (adult) HPP and pseudo‐HPP, respectively. A single dose of 3 × 1011 vector genomes per body (vg/b) was injected intramuscularly into 8‐week‐old AlplPrx1/Prx1 and wild‐type (WT) littermates, or into 3‐day‐old Phospho1−/− and WT mice, and treatment efficacy was evaluated after 60 days for late‐onset HPP mice and after 90 days for Phospho1−/− mice. Biochemical analysis showed sustained serum alkaline phosphatase activity and reduced plasma PPi levels, and radiographic images, micro‐computed tomography (micro‐CT) analysis, and hematoxylin and eosin (H&E) staining showed improvements in the long bones in the late‐onset HPP mice and corrected scoliosis in the Phospho1−/− mice. Micro‐CT analysis of the dentoalveolar complex did not reveal significant changes in the phenotype of late‐onset HPP and pseudo‐HPP models. Moreover, alizarin red staining analysis showed that AAV8‐TNAP‐D10 treatment did not promote ectopic calcification of soft organs in adult HPP mice after 60 days of treatment, even after inducing chronic kidney disease. Overall, the AAV8‐TNAP‐D10 treatment improved the skeletal phenotype in both the adult HPP and pseudo‐HPP mouse models. This preclinical study will contribute to the advancement of gene therapy for the improvement of skeletal disease in patients with heritable forms of osteomalacia. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Molecular Dissection of Somatic Skeletal Disease in Neurofibromatosis Type 1
Authors: Paria Nandina , Khalid Aysha , Shen Bo , Lemoine Ben , Chan Jinyan , Kidane Yared H , Oxendine Ila , Cornelia Reuel , Wise Carol A , Rios Jonathan J 
Published: December 2022

ABSTRACT
Neurofibromatosis type 1 (NF1) is a tumor predisposition syndrome caused by heterozygous NF1 gene mutations. Patients with NF1 present with pleiotropic somatic secondary manifestations, including development of bone pseudarthrosis after fracture. Somatic NF1 gene mutations were reproducibly identified in patient-derived pseudarthrosis specimens, suggesting a local mosaic cell population including somatic pathologic cells. The somatic cellular pathogenesis of NF1 pseudarthroses remains unclear, though defects in osteogenesis have been posited. Here, we applied time-series single-cell RNA-sequencing (scRNA-seq) to patient-matched control and pseudarthrosis-derived primary bone stromal cells (BSCs). We show that osteogenic specification to an osteoblast progenitor cell population was evident for control bone-derived cells and haploinsufficient pseudarthrosis-derived cells. Similar results were observed for somatic patient fracture-derived NF1−/− cells; however, expression of genetic pathways associated with skeletal mineralization were significantly reduced in NF1−/− cells compared with fracture-derived NF1+/− cells. In mice, we show that Nf1 expressed in bone marrow osteoprogenitors is required for the maintenance of the adult skeleton. Results from our study implicate impaired Clec11a-Itga11-Wnt signaling in the pathogenesis of NF1-associated skeletal disease. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Application of lncRNA–miRNA–mRNA ceRNA network analysis in the treatment of androgenic alopecia
Authors: Wei Hanxiao , Yi Tian , Li Qiang , Guo Yanping , Shen Caiqi , Jin Peisheng 
Published: December 2022

AbstractBackgroundLong noncoding RNAs (lncRNAs) can be used as competitive endogenous RNAs (ceRNAs) to bind to microRNAs (miRNAs) to regulate gene expression. Previous studies have demonstrated that ceRNAs play an important role in the development of tumors. However, it is not clear whether the lncRNA–miRNA–mRNA ceRNA network plays a role in androgenic alopecia (AGA).MethodsThe hair follicles of three AGA patients and three healthy individuals were collected for high‐throughput whole transcriptome sequencing to screen for differentially expressed lncRNAs. Differentially expressed lncRNA target genes were subjected to databases to predict miRNA–mRNA and lncRNA–miRNA relationship pairs, and a ceRNA network was constructed using Cytoscape software. Relative expression was verified by real‐time quantitative reverse transcription–polymerase chain reaction (qRT‐PCR).Results84 lncRNAs were significantly differentially expressed between the hair follicles of AGA patients and those of healthy individuals; 30 were upregulated, and 54 were downregulated. The top 10 upregulated lncRNAs were ENST00000501520, ENST00000448179, ENST00000318291, ENST00000568280, ENST00000561121, ENST00000376609, ENST00000602414, ENST00000573866, ENST00000513358, and ENST00000564194. The top 10 downregulated lncRNAs were ENST00000566804, ENST00000561973, ENST00000587680, ENST00000569927, ENST00000340444, ENST00000424345, ENST00000589787, NR_024344, NR_073026, and NR_110001. The qRT‐PCR validation results and receiver‐operating characteristic curve analysis indicated that one upregulated lncRNA, LOXL1‐AS1 (ENST00000564194), had the most significant clinical diagnostic potential. After further analysis, it was concluded that LOXL1‐AS1 could be used as a sponge to target hsa‐miR‐5193, thereby regulating TP53 expression.ConclusionThe ceRNA network‐regulating AGA was constructed through high‐throughput sequencing. Our study also identified a key lncRNA that is possibly related to the AGA pathological process.