bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors Influencing Clinical and MRI Outcomes of Mesenchymal Stem Cell Implantation With Concomitant High Tibial Osteotomy for Varus Knee Osteoarthritis
Authors: Kim Yong Sang , Suh Dong Suk , Tak Dae Hyun , Chung Pill Ku , Kwon Yoo Beom , Kim Tae Yong , Koh Yong Gon 
Published: February 2021

Background: Cartilage repair procedures using mesenchymal stem cells (MSCs) can provide superior cartilage regeneration in the medial compartment of the knee joint when high tibial osteotomy (HTO) is performed for varus knee osteoarthritis (OA). However, few studies have reported the factors influencing the outcomes of MSC implantation with concomitant HTO. Purpose: To investigate the outcomes of MSC implantation with concomitant HTO and to identify the prognostic factors that are associated with the outcomes. Study Design: Case series; Level of evidence, 4. Methods: A total of 71 patients (75 knees) were retrospectively evaluated after MSC implantation with concomitant HTO. Clinical and radiological outcomes were evaluated, and magnetic resonance imaging (MRI) was used to assess cartilage regeneration. Statistical analyses were performed to determine the effect of different factors on clinical, radiographic, and MRI outcomes. Results: Clinical and radiographic outcomes improved significantly from preoperatively to final follow-up ( P < .001 for all), and overall cartilage regeneration was encouraging. Significant correlations were found between clinical and MRI outcomes. However, radiographic outcomes were not significantly correlated with clinical or MRI outcomes. Patient age and number of MSCs showed significant correlations with clinical and MRI outcomes. On multivariate analyses, patient age and number of MSCs showed high prognostic significance with poor clinical outcomes. Conclusion: MSC implantation with concomitant HTO provided feasible cartilage regeneration and satisfactory clinical outcomes for patients with varus knee OA. Patient age and number of MSCs were important factors that influenced the clinical and MRI outcomes of MSC implantation with concomitant HTO for varus knee OA.
Biological Aging and Periodontal Disease: Analysis of NHANES (2001–2002)
Authors: Nguyen L.M. , Chon J.J. , Kim E.E. , Cheng J.C. , Ebersole J.L. 
Published: February 2021

Introduction: Periodontitis is a chronic inflammatory disease caused by multiple potential contributing factors such as bacterial biofilm infection of the tissues surrounding the teeth and environmental determinants and a dysregulated host response for modifying and resolving the inflammation. Because periodontal disease is a major public health concern with substantial increases in the prevalence and severity in aging populations, previous studies of periodontitis tended to approach the disease as an age-associated outcome across the life span. However, few investigations have considered that, as a chronic noncommunicable disease, periodontitis may not simply be a disease that increases with age but may contribute to more rapid biologic aging. Objectives: Increasing population data supports the potential disconnect between chronological aging and biologic aging, which would contribute to the heterogeneity of aging phenotypes within chronologic ages across populations. Thus, our aim was to test whether periodontal disease affects biological aging across the life span. Methods: The prevalence of periodontitis in the adult US population is a portion of the assessment of the National Health and Nutrition Examination Survey (NHANES), which has been ongoing since 1971 through 2-y cycles sampling populations across the country. We used NHANES 2001–2002 to test the hypothesis that the presence/severity of periodontal disease as an exposure variable would negatively affect telomere length, a measure of biological aging, and that this relationship is modified by factors that also affect the progression of periodontitis, such as sex, race/ethnicity, and smoking. Results: The data demonstrated a significant impact of periodontitis on decreasing telomere lengths across the life span. These differences were modulated by age, sex, race/ethnicity, and smoking within the population. Conclusion: The findings lay the groundwork for future studies documenting broader effects on biological aging parameters as well as potential intervention strategies for periodontitis in driving unhealthy aging processes. Knowledge Transfer Statement: Periodontitis is a chronic inflammatory disease and dysregulated host response. Shortening of telomeres is a reflection of biologic aging. Decreased telomere lengths with periodontitis are seemingly related to chronic infection and persistent local and systemic inflammation. These findings suggest that periodontitis is not simply a disease of aging but may also transmit chronic systemic signals that could affect more rapid biological aging. Clinicians can use this outcome to recognize the role of periodontitis in driving unhealthy aging processes in patients.
Pharmacologic targeting of plasma cell endoplasmic reticulum proteostasis to reduce amyloidogenic light chain secretion
Authors: Rius Bibiana , Mesgarzadeh Jaleh S. , Romine Isabelle C. , Paxman Ryan J. , Kelly Jeffery W. , Wiseman R. Luke 
Published: February 2021

Abstract
Light chain (LC) amyloidosis (AL) involves the toxic aggregation of amyloidogenic immunoglobulin LCs secreted from a clonal expansion of diseased plasma cells. Current AL treatments use chemotherapeutics to ablate the AL plasma cell population. However, no treatments are available that directly reduce the toxic LC aggregation involved in AL pathogenesis. An attractive strategy to reduce toxic LC aggregation in AL involves enhancing endoplasmic reticulum (ER) proteostasis in plasma cells to reduce the secretion and subsequent aggregation of amyloidogenic LCs. Here, we show that the ER proteostasis regulator compound 147 reduces secretion of an amyloidogenic LC as aggregation-prone monomers and dimers in AL patient–derived plasma cells. Compound 147 was established to promote ER proteostasis remodeling by activating the ATF6 unfolded protein response signaling pathway through a mechanism involving covalent modification of ER protein disulfide isomerases (PDIs). However, we show that 147-dependent reductions in amyloidogenic LCs are independent of ATF6 activation. Instead, 147 reduces amyloidogenic LC secretion through the selective, on-target covalent modification of ER proteostasis factors, including PDIs, revealing an alternative mechanism by which this compound can influence ER proteostasis of amyloidogenic proteins. Importantly, compound 147 does not interfere with AL plasma cell toxicity induced by bortezomib, a standard chemotherapeutic used to ablate the underlying diseased plasma cells in AL. This shows that pharmacologic targeting of ER proteostasis through selective covalent modification of ER proteostasis factors is a strategy that can be used in combination with chemotherapeutics to reduce the LC toxicity associated with AL pathogenesis.
Patients with triple-negative, JAK2V617F- and CALR-mutated essential thrombocythemia share a unique gene expression signature
Authors: Alimam Samah , Villiers William , Dillon Richard , Simpson Michael , Runglall Manohursingh , Smith Alexander , Chatzikyriakou Prodromos , Lavender Paul , Kanda Anju , Mills Ken , Bellosillo Paricio Beatriz , Kaufman-Cook James , Ord Sophie , Kordasti Shahram , Radia Deepti , Woodley Claire , Francis Yvonne , Mufti Ghulam , McLornan Donal P. , Harrison Claire N. 
Published: February 2021

Abstract
Approximately 10% to 15% of patients with essential thrombocythemia (ET) lack the common driver mutations, so-called “triple-negative” (TN) disease. We undertook a systematic approach to investigate for somatic mutations and delineate gene expression signatures in 46 TN patients and compared the results to those with known driver mutations and healthy volunteers. Deep, error-corrected, next-generation sequencing of peripheral blood mononuclear cells using the HaloPlexHS platform and whole-exome sequencing was performed. Using this platform, 10 (22%) of 46 patients had detectable mutations (MPL, n = 6; JAK2V617F, n = 4) with 3 of 10 cases harboring germline MPL mutations. RNA-sequencing and DNA methylation analysis were also performed by using peripheral blood mononuclear cells. Pathway analysis comparing healthy volunteers and ET patients (regardless of mutational status) identified significant enrichment for genes in the tumor necrosis factor, NFκB, and MAPK pathways and upregulation of platelet proliferative drivers such as ITGA2B and ITGB3. Correlation with DNA methylation showed a consistent pattern of hypomethylation at upregulated gene promoters. Interrogation of these promoter regions highlighted enrichment of transcriptional regulators, which were significantly upregulated in patients with ET regardless of mutation status, including CEBPβ and NFκB. For “true” TN ET, patterns of gene expression and DNA methylation were similar to those in ET patients with known driver mutations. These observations suggest that the resultant ET phenotype may, at least in part and regardless of mutation type, be driven by transcriptional misregulation and may propagate downstream via the MAPK, tumor necrosis factor, and NFκB pathways with resultant JAK-STAT activation. These findings identify potential novel mechanisms of disease initiation that require further evaluation.
Daratumumab plus RVd for newly diagnosed multiple myeloma: final analysis of the safety run-in cohort of GRIFFIN
Authors: Voorhees Peter M. , Rodriguez Cesar , Reeves Brandi , Nathwani Nitya , Costa Luciano J. , Lutska Yana , Bobba Padma , Hoehn Daniela , Pei Huiling , Ukropec Jon , Qi Ming , Lin Thomas S. , Richardson Paul G. 
Published: February 2021

Abstract
The phase 2 GRIFFIN study of daratumumab plus lenalidomide/bortezomib/dexamethasone (D-RVd) for transplant-eligible, newly diagnosed multiple myeloma included a safety run-in phase followed by a randomized phase. The ongoing randomized phase has met its prespecified primary end point of an improved stringent complete response (sCR) rate after consolidation for D-RVd (reported elsewhere). Final analysis of the safety run-in cohort is reported herein and provides longer follow-up (median, 40.8 months) encompassing daratumumab plus lenalidomide (D-R) maintenance therapy. Patients in the safety run-in cohort (N = 16) received 4 induction cycles (D-RVd), high-dose melphalan supported by autologous stem cell transplant, 2 consolidation cycles (D-RVd), and 24 months of maintenance (D-R). By the end of consolidation, all patients had responded, with a best response of sCR in 9 (56.3%) patients; 8 (50.0%) patients were minimal residual disease (MRD) negative (10‒5 threshold). After maintenance, 15 (93.8%) patients had achieved a best response of sCR, and 13 (81.3%) patients were MRD (10‒5) negative. Estimated 36-month progression-free and overall survival rates were 78.1% and 93.8%, respectively. One death from progressive disease occurred in the patient who did not achieve sCR. Observed safety profiles were consistent with daratumumab and RVd. With &gt;3 years of median follow-up, D-RVd achieved durable responses that deepened with D-R maintenance. This study was registered at www.clinicaltrials.gov as #NCT02874742.
Effects of non-driving related tasks on mental workload and take-over times during conditional automated driving
Authors: Müller Andreas Lars , Fernandes-Estrela Natacha , Hetfleisch Ruben , Zecha Lukas , Abendroth Bettina 
Published: February 2021

Abstract
Background
Automated driving will be of high value in the future. While in partial-automated driving the driver must always monitor the traffic situation, a paradigm shift is taking place in the case of conditional automated driving (Level 3 according to SAE). From this level of automation onwards, the vehicle user is released from permanent vehicle control and environmental monitoring and is allowed to engage in Non-Driving Related Tasks (NDRT) in his or her newly gained spare time. These tasks can be performed until a take-over request informs the user to resume vehicle control. As the driver is still considered to be the fall-back level, this aspect of taking over control is considered especially critical.

Methods
While previous research projects have focused their studies on the factors influencing the take-over request, this paper focuses on the effects of NDRT on the user of the vehicle during conditional automated driving, especially on the human workload. NDRT (such as Reading, Listening, Watching a movie, Texting and Monitoring ride) were examined within a static driving simulator at the Institute of Ergonomics & Human Factors with 56 participants in an urban environment. These NDRT were tested for mental workload and the ability to take over in a critical situation. To determine the perceived workload, the subjective workload, psychophysiological activity as well as performance-based parameters of a secondary competing task performed by a were used.

Results
This study revealed that the selected NDRT vary significantly in their mental workload and that the workload correlates with the length of the time needed for take over control. NDRT which are associated with a high workload (such as Reading or Texting) also lead to longer reaction times.
Interaction of Arsenophonus with Wolbachia in Nilaparvata lugens
Authors: Guo Huifang , Wang Na , Niu Hongtao , Zhao Dongxiao , Zhang Zhichun 
Published: February 2021

Abstract
Background
Co-infection of endosymbionts in the same host is ubiquitous, and the interactions of the most common symbiont Wolbachia with other symbionts, including Spiroplasma, in invertebrate organisms have received increasing attention. However, the interactions between Wolbachia and Arsenophonus, another widely distributed symbiont in nature, are poorly understood. We tested the co-infection of Wolbachia and Arsenophonus in different populations of Nilaparvata lugens and investigated whether co-infection affected the population size of the symbionts in their host.

Results
A significant difference was observed in the co-infection incidence of Wolbachia and Arsenophonus among 5 populations of N. lugens from China, with nearly half of the individuals in the Zhenjiang population harbouring the two symbionts simultaneously, and the rate of occurrence was significantly higher than that of the other 4 populations. The Arsenophonus density in the superinfection line was significantly higher only in the Maanshan population compared with that of the single-infection line. Differences in the density of Wolbachia and Arsenophonus were found in all the tested double-infection lines, and the dominant symbiont species varied with the population only in the Nanjing population, with Arsenophonus the overall dominant symbiont.

Conclusions
Wolbachia and Arsenophonus could coexist in N. lugens, and the co-infection incidence varied with the geographic populations. Antagonistic interactions were not observed between Arsenophonus and Wolbachia, and the latter was the dominant symbiont in most populations.
Physical mapping of repetitive oligonucleotides facilitates the establishment of a genome map-based karyotype to identify chromosomal variations in peanut
Authors: Fu Liuyang , Wang Qian , Li Lina , Lang Tao , Guo Junjia , Wang Siyu , Sun Ziqi , Han Suoyi , Huang Bingyan , Dong Wenzhao , Zhang Xinyou , Du Pei 
Published: February 2021

Abstract
Background
Chromosomal variants play important roles in crop breeding and genetic research. The development of single-stranded oligonucleotide (oligo) probes simplifies the process of fluorescence in situ hybridization (FISH) and facilitates chromosomal identification in many species. Genome sequencing provides rich resources for the development of oligo probes. However, little progress has been made in peanut due to the lack of efficient chromosomal markers. Until now, the identification of chromosomal variants in peanut has remained a challenge.

Results
A total of 114 new oligo probes were developed based on the genome-wide tandem repeats (TRs) identified from the reference sequences of the peanut variety Tifrunner (AABB, 2n = 4x = 40) and the diploid species Arachis ipaensis (BB, 2n = 2x = 20). These oligo probes were classified into 28 types based on their positions and overlapping signals in chromosomes. For each type, a representative oligo was selected and modified with green fluorescein 6-carboxyfluorescein (FAM) or red fluorescein 6-carboxytetramethylrhodamine (TAMRA). Two cocktails, Multiplex #3 and Multiplex #4, were developed by pooling the fluorophore conjugated probes. Multiplex #3 included FAM-modified oligo TIF-439, oligo TIF-185-1, oligo TIF-134-3 and oligo TIF-165. Multiplex #4 included TAMRA-modified oligo Ipa-1162, oligo Ipa-1137, oligo DP-1 and oligo DP-5. Each cocktail enabled the establishment of a genome map-based karyotype after sequential FISH/genomic in situ hybridization (GISH) and in silico mapping. Furthermore, we identified 14 chromosomal variants of the peanut induced by radiation exposure. A total of 28 representative probes were further chromosomally mapped onto the new karyotype. Among the probes, eight were mapped in the secondary constrictions, intercalary and terminal regions; four were B genome-specific; one was chromosome-specific; and the remaining 15 were extensively mapped in the pericentric regions of the chromosomes.

Conclusions
The development of new oligo probes provides an effective set of tools which can be used to distinguish the various chromosomes of the peanut. Physical mapping by FISH reveals the genomic organization of repetitive oligos in peanut chromosomes. A genome map-based karyotype was established and used for the identification of chromosome variations in peanut following comparisons with their reference sequence positions.
Loss of mature D1 leads to compromised CP43 assembly in Arabidopsis thaliana
Authors: Shi Yafei , Che Yufen , Wang Yukun , Luan Sheng , Hou Xin 
Published: February 2021

Abstract
Background
Photosystem II (PSII) is a highly conserved integral-membrane multi-subunit pigment-protein complex. The proteins, pigments, lipids, and ions in PSII need to be assembled precisely to ensure a proper PSII biogenesis. D1 is the main subunit of PSII core reaction center (RC), and is usually synthesized as a precursor D1. D1 maturation by the C-terminal processing protease CtpA is essential for PSII assembly. However, the detailed mechanism about how D1 maturation affects PSII assembly is not clearly elucidated so far. In this study, Arabidopsis thaliana CtpA mutant (atctpa: SALK_056011), which lacks the D1 mature process, was used to investigate the function of this process on PSII assembly in more details.

Results
Without the C-terminal processing of precursor D1, PSII assembly, including PSII monomer, dimer, especially PSII supercomplexes (PSII SCs), was largely compromised as reported previously. Western blotting following the BN-2D-SDS PAGE revealed that although the assembly of PSII core proteins D2, CP43 and CP47 was affected by the loss of D1 mature process, the incorporation of CP43 was affected the most, indicated by its most reduced assembly efficiency into PSII SCs. Furthermore, the slower growth of yeast cells which were co-transformed with pD1 and CP43, when compared with the ones co-transformed with mature D1 and CP43, approved the existence of D1 C-terminal tail hindered the interaction efficiency between D1 and CP43, indicating the physiological importance of D1 mature process on the PSII assembly and the healthy growth of the organisms.

Conclusions
The knockout Arabidopsis atctpa mutant is a good material to study the unexpected link between D1 maturation and PSII SCs assembly. The loss of D1 maturation mainly affects the incorporation of PSII core protein CP43, an inner antenna binding protein, which functions in the association of LHCII complexes to PSII dimers during the formation of PSII SCs. Our findings here provide detailed supports of the role of D1 maturation during PSII SCs assembly in higher plants.
How many general practice consultations occur in Ireland annually? Cross-sectional data from a survey of general practices
Authors: Collins C. , Homeniuk R. 
Published: February 2021

Abstract
Background
General practice plays a central role in the Irish health system. This study aimed to determine a baseline estimate of the number of consultations completed in general practice in Ireland annually to facilitate evidence-based healthcare planning.

Methods
A survey was emailed to all 3378 individual members of the Irish College of General Practitioners in February 2020 asking each practice to report on consultations by general practitioners and practice nurses occurring on the previous day of practice.

Results
A total of 507 practices responded to the survey, reporting 34,594 general practitioner consultations and 13,161 nurse consultations on one day. Extrapolating this figure nationally, we estimate 21,353,731 GP consultations and 7,749,615 practice nurse consultations occur in Ireland annually. An Irish person visits their GP an estimated 4.34 times a year and the average consultation time is 13.7 min.

Conclusions
This study shows that over 29.1 million consultations take place in Irish general practice every year. Innovative interventions to increase the capacity of general practice are needed to ensure high-quality care continues to be accessible in Ireland.