bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-cell RNA sequencing reveals rebalancing of immunological response in patients with periodontitis after non-surgical periodontal therapy
Authors: Lee Hansong , Joo Ji-Young , Sohn Dong Hyun , Kang Junho , Yu Yeuni , Park Hae Ryoun , Kim Yun Hak 
Published: November 2022

AbstractBackgroundPeriodontitis is a major inflammatory disease of the oral mucosa that is not limited to the oral cavity but also has systemic consequences. Although the importance of chronic periodontitis has been emphasized, the systemic immune response induced by periodontitis and its therapeutic effects remain elusive. Here, we report the transcriptomes of peripheral blood mononuclear cells (PBMCs) from patients with periodontitis.MethodsUsing single-cell RNA sequencing, we profiled PBMCs from healthy controls and paired pre- and post-treatment patients with periodontitis. We extracted differentially expressed genes and biological pathways for each cell type and calculated activity scores reflecting cellular characteristics. Intercellular crosstalk was classified into therapy-responsive and -nonresponsive pathways.ResultsWe analyzed pan-cellular differentially expressed genes caused by periodontitis and found that most cell types showed a significant increase inCRIP1, which was further supported by the increased levels of plasma CRIP1 observed in patients with periodontitis. In addition, activated cell type-specific ligand-receptor interactions, including the BTLA, IFN-γ, and RESISTIN pathways, were prominent in patients with periodontitis. Both the BTLA and IFN-γ pathways returned to similar levels in healthy controls after periodontal therapy, whereas the RESISTIN pathway was still activated even after therapy.ConclusionThese data collectively provide insights into the transcriptome changes and molecular interactions that are responsive to periodontal treatment. We identified periodontitis-specific systemic inflammatory indicators and suggest unresolved signals of non-surgical therapy as future therapeutic targets.
Sepax-2 cell processing device: a study assessing reproducibility of concentrating thawed hematopoietic progenitor cells
Authors: Mfarrej Bechara , Vicari Olivier , Ouffai Sarah , Malenfant Carine , Granata Angela , Thevenet Sophie , Chabannon Christian , Lemarié Claude , Calmels Boris 
Published: November 2022

Abstract
Background
Autologous hematopoietic progenitor cell (HPC) transplantation is currently the standard of care for a fraction of patients with newly diagnosed myelomas and relapsed or refractory lymphomas. After high-dose chemotherapy, cryopreserved HPC are either infused directly after bedside thawing or washed and concentrated before infusion. We previously reported on the comparability of washing/concentrating HPC post-thaw vs. infusion without manipulation in terms of hematopoietic engraftment, yet settled for the prior favoring cell debris and DMSO removal. For almost two decades, automation of this critical step of washing/concentrating cells has been feasible. As part of continuous process verification, we aim to evaluate reproducibility of this procedure by assessing intra-batch and inter-batch variability upon concentration of thawed HPC products using the Sepax 2 S-100 cell separation system.

Methods
Autologous HPC collected from the same patient were thawed and washed either in two batches processed within a 3-4 h interval and immediately infused on the same day (intra-batch, n = 45), or in two batches on different days (inter-batch, n = 49) for those patients requiring 2 or more high-dose chemotherapy cycles. Quality attributes assessed were CD34+ cell recovery, viability and CD45+ viability; CFU assay was only performed for allogeneic grafts.

Results
Intra-batch and inter-batch median CD34+ cell recovery was comparable (75% vs. 73% and 77% vs. 77%, respectively). Similarly, intra-batch and inter-batch median CD45+ cell viability was comparable (79% vs. 80% and 79% vs. 78%, respectively). Bland-Altman analysis describing agreement between batches per patient revealed a bias close to 0%. Additionally, lower HPC recoveries noted in batch 1 were noted as well in batch 2, regardless of the CD34+ cell dose before cryopreservation, both intra- and inter-batch, suggesting that the quality of the collected product plays an important role in downstream recovery. Intrinsic (high mature and immature granulocyte content) and extrinsic (delay between apheresis and cryopreservation) variables of the collected product resulted in a significantly lower CD45+ viability and CD34+ cell recovery upon thawing/washing.

Conclusions
Automated post-thaw HPC concentration provides reproducible cell recoveries and viabilities between different batches. Implications of this work go beyond HPC to concentrate cell suspension/products during manufacturing of cell and gene therapy products.
Evidence that the pituitary gland connects type 2 diabetes mellitus and schizophrenia based on large-scale trans-ethnic genetic analyses
Authors: Cai Lei , Sun Yanlan , Liu Yonglin , Chen Wenzhong , He Lin , Wei Dong-Qing 
Published: November 2022

AbstractBackgroundPrevious studies on European (EUR) samples have obtained inconsistent results regarding the genetic correlation between type 2 diabetes mellitus (T2DM) and Schizophrenia (SCZ). A large-scale trans-ethnic genetic analysis may provide additional evidence with enhanced power.ObjectiveWe aimed to explore the genetic basis for both T2DM and SCZ based on large-scale genetic analyses of genome-wide association study (GWAS) data from both East Asian (EAS) and EUR subjects.MethodsA range of complementary approaches were employed to cross-validate the genetic correlation between T2DM and SCZ at the whole genome, autosomes (linkage disequilibrium score regression, LDSC), loci (Heritability Estimation from Summary Statistics, HESS), and causal variants (MiXeR and Mendelian randomization, MR) levels. Then, genome-wide and transcriptome-wide cross-trait/ethnic meta-analyses were performed separately to explore the effective shared organs, cells and molecular pathways.ResultsA weak genome-wide negative genetic correlation between SCZ and T2DM was found for the EUR (rg = − 0.098,P = 0.009) and EAS (rg=- 0.053 andP = 0.032) populations, which showed no significant difference between the EUR and EAS populations (P = 0.22). After Bonferroni correction, the rgremained significant only in the EUR population. Similar results were obtained from analyses at the levels of autosomes, loci and causal variants. 25 independent variants were firstly identified as being responsible for both SCZ and T2DM. The variants associated with the two disorders were significantly correlated to the gene expression profiles in the brain (P = 1.1E-9) and pituitary gland (P = 1.9E-6). Then, 61 protein-coding and non-coding genes were identified as effective genes in the pituitary gland (P < 9.23E-6) and were enriched in metabolic pathways related to glutathione mediated arsenate detoxification and to D-myo-inositol-trisphosphate.ConclusionHere, we show that a negative genetic correlation exists between SCZ and T2DM at the whole genome, autosome, locus and causal variant levels. We identify pituitary gland as a common effective organ for both diseases, in which non-protein-coding effective genes, such as lncRNAs, may be responsible for the negative genetic correlation. This highlights the importance of molecular metabolism and neuroendocrine modulation in the pituitary gland, which may be responsible for the initiation of T2DM in SCZ patients.
Learning-based control approaches for service robots on cloth manipulation and dressing assistance: a comprehensive review
Authors: Nocentini Olivia , Kim Jaeseok , Bashir Zain Muhammad , Cavallo Filippo 
Published: November 2022

AbstractBackgroundService robots are defined as reprogrammable, sensor-based mechatronic devices that perform useful services in an autonomous or semi-autonomous way to human activities in an everyday environment. As the number of elderly people grows, service robots, which can operate complex tasks like dressing tasks for disabled people, are being demanded increasingly. Consequently, there is a growing interest in studying dressing tasks, such as putting on a t-shirt, a hat, or shoes. Service robots or robot manipulators have been developed to accomplish these tasks using several control approaches. The robots used in this kind of application are usually bimanual manipulator (i.e. Baxter robot) or single manipulators (i.e. Ur5 robot). These arms are usually used for recognizing clothes and then folding them or putting an item on the arm or on the head of a person.MethodsThis work provides a comprehensive review of the most relevant attempts/works of robotic dressing assistance with a focus on the control methodology used for dressing tasks. Three main areas of control methods for dressing tasks are proposed: Supervised Learning (SL), Learning from Demonstration (LfD), and Reinforcement Learning (RL). There are also other methods that cannot be classified into these three areas and hence they have been placed in the other methods section. This research was conducted within three databases: Scopus, Web of Science, and Google Scholar. Accurate exclusion criteria were applied to screen the 2594 articles found (at the end 39 articles were selected). For each work, an evaluation of the model is made.ConclusionCurrent research in cloth manipulation and dressing assistance focuses on learning-based robot control approach. Inferring the cloth state is integral to learning the manipulation and current research uses principles of Computer Vision to address the issue. This makes the larger problem of control robot based on learning data-intensive; therefore, a pressing need for standardized datasets representing different cloth shapes, types, materials, and human demonstrations (for LfD) exists. Simultaneously, efficient simulation capabilities, which closely model the deformation of clothes, are required to bridge the reality gap between the real-world and virtual environments for deploying the RL trial and error paradigm. Such powerful simulators are also vital to collect valuable data to train SL and LfD algorithms that will help reduce human workload.
Limb accelerations during sleep are related to measures of strength, sensation, and spasticity among individuals with spinal cord injury
Authors: Rigot Stephanie K. , Boninger Michael L. , Ding Dan , Collinger Jennifer L. , Dicianno Brad E. , Worobey Lynn A. 
Published: November 2022

Abstract
Background
To evaluate the relationship between measures of neuromuscular impairment and limb accelerations (LA) collected during sleep among individuals with chronic spinal cord injury (SCI) to provide evidence of construct and concurrent validity for LA as a clinically meaningful measure.

Methods
The strength (lower extremity motor score), sensation (summed lower limb light touch scores), and spasticity (categorized lower limb Modified Ashworth Scale) were measured from 40 adults with chronic (≥ 1 year) SCI. Demographics, pain, sleep quality, and other covariate or confounding factors were measured using self-report questionnaires. Each participant then wore ActiGraph GT9X Link accelerometers on their ankles and wrist continuously for 1–5 days to measure LA from movements during sleep. Regression models with built-in feature selection were used to determine the most relevant LA features and the association to each measure of impairment.

Results
LA features were related to measures of impairment with models explaining 69% and 73% of the variance (R²) in strength and sensation, respectively, and correctly classifying 81.6% (F1-score = 0.814) of the participants into spasticity categories. The most commonly selected LA features included measures of power and frequency (frequency domain), movement direction (correlation between axes), consistency between movements (relation to recent movements), and wavelet energy (signal characteristics). Rolling speed (change in angle of inclination) and movement smoothness (median crossings) were uniquely associated with strength. When LA features were included, an increase of 72% and 222% of the variance was explained for strength and sensation scores, respectively, and there was a 34% increase in spasticity classification accuracy compared to models containing only covariate features such as demographics, sleep quality, and pain.

Conclusion
LA features have shown evidence of having construct and concurrent validity, thus demonstrating that LA are a clinically-relevant measure related to lower limb strength, sensation, and spasticity after SCI. LA may be useful as a more detailed measure of impairment for applications such as clinical prediction models for ambulation.
Is the postoperative pedicle screw position after dorsal instrumentation with or without intraoperative cone beam CT imaging worse in patients with obesity than in normal-weight patients?
Authors: Zimmermann Felix , Kohl Katharina , Mandelka Eric , Grützner Paul A. , Franke Jochen , Vetter Sven Y. 
Published: November 2022

Abstract
Background
Intraoperative cone beam CT (CBCT) imaging in dorsal instrumentation facilitates pedicle screw positioning. However, in patients with obesity, the benefit may be reduced due to artifacts that affect image quality. The purpose of this study was to evaluate whether intraoperative CBCT leads to an improved postoperative screw position compared to conventional fluoroscopy independent of body weight.

Methods
A total of 71 patients (18 patients with a BMI > 30 kg/m2, 53 patients with a BMI < 30 kg/m2) who underwent dorsal instrumentation with intraoperative CBCT imaging were included in study groups one (SG1) and two (SG2). Two control groups (CG1 and CG2) were randomly sampled to include 22 patients with a BMI > 30 kg/m2 and 60 patients with a BMI < 30 kg/m2 who underwent dorsal instrumentation without intraoperative CBCT imaging. The pedicle screw position in postoperative computed tomography was assessed using the Gertzbein–Robbins classification.

Results
In SG1 (BMI > 30 kg/m2), a total of 107 (83.6%) pedicle screws showed no relevant perforation (type A + B), and 21 (16.4%) pedicle screws showed relevant perforation (type C − E). In SG2 (BMI < 30 kg/m2), 328 (90.9%) screws were classified as type A + B, and 33 (9.1%) screws were classified as type C − E. In CG1 (BMI > 30 kg/m2), 102 (76.1%) pedicle screws showed no relevant perforation (type A + B), and 32 (23.9%) pedicle screws showed relevant perforation (type C − E). In CG2 (BMI < 30 kg/m2), 279 (76.9%) screws were classified as type A + B, and 84 (23.1%) screws were classified as type C − E. There were significant differences between the values of SG1 and SG2 (p = 0.03) and between the values of SG2 and CG2 (p < 0.0001).

Conclusion
CBCT imaging in dorsal instrumentation can lead to an improved pedicle screw position among both patients with obesity and normal-weight patients. However, patients with obesity showed significantly worse pedicle screw positions postoperatively after dorsal instrumentation with intraoperative CBCT imaging than normal-weight patients.
The importance of early diagnosis and views on newborn screening in metachromatic leukodystrophy: results of a Caregiver Survey in the UK and Republic of Ireland
Authors: Morton Georgina , Thomas Sophie , Roberts Pat , Clark Vivienne , Imrie Jackie , Morrison Alexandra 
Published: November 2022

AbstractMetachromatic Leukodystrophy (MLD) is a rare, autosomal recessive lysosomal storage disorder caused by a deficiency of the enzyme arylsulfatase A (ARSA). MLD causes progressive loss of motor function and severe decline in cognitive function, leading to premature death. Early diagnosis of MLD provides the opportunity to begin treatment before the disease progresses and causes severe disability. MLD is not currently included in newborn screening (NBS) in the UK.This study consisted of an online survey, and follow-up semi-structured interviews open to MLD patients or caregivers, aged 18 years and over. The aims of the study were to understand the importance of early diagnosis and to establish the views of families and caregivers of patients with MLD on NBS.A total of 24 patients took part in the survey, representing 20 families (two families had two children with MLD, one family had three children with MLD). Following on from the survey, six parents participated in the interviews. Our data showed diagnostic delay from first symptoms was between 0 and 3 years, with a median of 1 year (n = 18); during this time deterioration was rapid, especially in earlier onset MLD. In patients with late infantile MLD (n = 10), 50% were wheelchair dependent, 30% were unable to speak, and 50% were tube fed when a diagnosis of MLD was confirmed. In patients with early juvenile MLD (n = 5), over half used a wheelchair some of the time, had uncontrollable crying, and difficulty speaking (all 60%) before or at the time of diagnosis. A high degree of support was expressed for NBS among caregivers, 95% described it as very or extremely important and 86% believed detection of MLD at birth would have changed their child’s future. One parent expressed their gratitude for an early diagnosis as a result of familial MLD screening offered at birth and how it had changed their child’s future: “It did and it absolutely has I will be forever grateful for his early diagnosis thanks to his older sister.”The rapid rate of deterioration in MLD makes it an essential candidate for NBS, particularly now the first gene therapy (Libmeldy™) has been approved by the European Medicines Agency. Libmeldy™ has also been recommended as a treatment option in England and Wales by the National Institute for Health and Care Excellence (NICE) and is being made available to patients in Scotland via the Scottish Medicines Consortium’s ultra-orphan pathway.
Novel approach to idursulfase and laronidase desensitization in type 2 and type 1 S mucopolysaccharidosis (MPS)
Authors: Spataro Federico , Viggiani Fabio , Macchia Domenico Giorgio , Rollo Valentina , Tummolo Albina , Suppressa Patrizia , Sabba’ Carlo , Rossi Maria Pia , Giliberti Lucia , Satriano Francesco , Nettis Eustachio , Di Bona Danilo , Caiaffa Maria Filomena , Fischetto Rita , Macchia Luigi 
Published: November 2022

Abstract
Background:
Idursulfase and laronidase are drugs used to treat Hunter syndrome (mucopolysaccharidosis type 2) and Scheie syndrome (mucopolysaccharidosis type 1 S), respectively. These are rare lysosomal storage disorders, leading to accumulation of glycosaminoglycans within lysosomes. Failure of early recognition of the disease and/or delay in starting the appropriate treatment result in severe clinical impairment and death. For almost 20 years, enzyme replacement therapy with recombinant proteins has represented the first line therapeutic option. However, administration of idursulfase and laronidase is associated with infusion-related hypersensitivity reactions, in approx. 20% of patients. In these patients, rapid desensitization by intravenous administration protocols has been used in order to avoid treatment discontinuation. This approach proved effective and safe. However, long-term tolerance could not be achieved. Thus, we decided to combine rapid desensitization with allergen immunotherapy-like desensitization.

Results:
Two patients with Hunter syndrome and one patient with Scheie syndrome developed severe allergy to idursulfase and laronidase, respectively, preventing them from continuing the otherwise indispensable therapy. In all three patients, the possible IgE-mediated nature of the reactions suffered was suggested by positive skin tests with the two enzymes, respectively. By devising 12-step, 3-dilution rapid desensitization protocols, we resumed the enzyme replacement therapy. However, the prolonged time required for administration (a not negligible pitfall, since therapy should be given weekly for life) and the persistent occurrence of reactions (mild but still requiring anti-allergic medication at full dosage) led us to combine rapid desensitization with a compact 11-step, 24-day allergen immunotherapy-like desensitization protocol. Thus, idursulfase and laronidase were injected subcutaneously, with a 500-fold increase from step 1 to step 11 for idursulfase and a 222-fold increase for laronidase. This strategy led to restoration of long-term tolerance, allowing weekly intravenous therapy administration under standard conditions, according to the manufacturer instructions, in the absence of side effects and with only precautionary low-dose premedication.

Conclusion:
Rapid desensitization is a suitable and safe option in the case of idursulfase and laronidase allergy. Combination with subcutaneous allergen immunotherapy-like desensitization afforded restoration of enzyme replacement therapy given by the normal administration schedule, by inducing sustained tolerance.
Telehealth exercise to Improve Physical function and frailty in patients with multiple myeloma treated with autologous hematopoietic Stem cell transplantation (TIPS): protocol of a randomized controlled trial
Authors: Lee Kyuwan , Nathwani Nitya , Shamunee Justin , Lindenfeld Lanie , Wong F. Lennie , Krishnan Amrita , Armenian Saro 
Published: November 2022

Abstract
Background
Advances in autologous hematopoietic stem cell transplantation (HSCT) and supportive care have led to marked improvements in survival for patients with multiple myeloma. Despite these improvements, patients with multiple myeloma remain at high risk of physical dysfunction and frailty due to HSCT and its associated exposures. Although traditional supervised exercise programs can improve frailty in cancer patients and survivors, rehabilitation facilities are typically far from a patient’s residence, are offered on fixed days/hours, contain uniform activities for everyone, and carry a higher risk of contact cross-infection due to immunosuppression, which can be barriers to exercise participation. Innovative personalized interventions are needed to overcome the limitations of traditional exercise interventions. The purpose of this study is to determine the efficacy and sustainability of a telehealth exercise intervention on physical function and frailty in patients with multiple myeloma treated with HSCT.

Methods
This randomized controlled trial will assess the efficacy of an 8-week telehealth exercise intervention in 60 patients with multiple myeloma who underwent autologous HSCT (30–180 days post-transplant) and are pre-frail or frail. There will be 30 intervention participants and 30 delayed controls. We will administer remote baseline assessments (week 0), followed by an 8-week telehealth intervention (week 1–8), post assessment (week 9), and an additional follow-up assessment (week 17). Our primary endpoint will be improved physical function, as assessed by the Short Physical Performance Battery test. Our secondary endpoint will be a decrease in frailty characteristics such as gait speed, strength, and fatigue. We will also evaluate the sustainability of improved physical function and frailty at week 17. Participants randomized to the intervention group will perform at least 90 min of exercise per week throughout the 8 weeks.

Discussion
This study will help optimize the delivery of safe, low-cost, and scalable telehealth exercise interventions to improve health outcomes in patients with multiple myeloma, an understudied population at high risk for physical dysfunction and frailty. Our study may provide the foundation for sustainable telehealth exercise interventions to improve physical function and frailty for other hematologic cancer patients (e.g., acute leukemia, lymphoma) as well as any other cancer population of interest.

Trial registration
ClinicalTrials.govNCT05142371. This study was retrospectively registered on December 2nd, 2021, and is currently open to accrual.