bluuebunny/crossref_metadata_2025 huggingface dataset:
Shattered States: Reconstituting Political Authority in the Aftermath of Civil War in Russia and Greece
Authors: Kokosalakis Yiannis
Published: November 2022

This article examines the process of disintegration and reconstitution of political authority in civil war with reference to the Russian (1918–1921) and Greek (1946–1949) civil wars. These conflicts bracket the post-World War I period of revolutionary and counterrevolutionary conflicts that has been the core subject of historical scholarship on European civil strife. Both cases were highly polarised clashes between establishment and revolutionary forces, and much of the relevant historiography has been naturally coloured by this aspect of the conflicts. I argue that the interpretative focus on polarisation obscures a different dynamic that is equally important for our understanding of civil war as a type of military conflict and, crucially, its political aftermath. Civil war in Russia and Greece did not emerge as a result of functioning states splitting into two or more competing authorities. It was rather the product of a multifaceted fragmentation of political power as a result of war and revolution; a shattering of the state into an array of asymmetrical actors competing for control over both its territory and its administrative resources. Polarisation followed this fragmentation, as these disparate actors manoeuvred to form the camps of the civil wars. This form of coalition building was a dynamic process in which armed violence was not only the chief means of resolution of the competing claims to power but also an essential factor in the formation of the sides themselves. A corollary of this is that the process of political reconstruction that follows civil war is determined as much by the imperative to work out a functioning relationship between the various elements of the victors’ camp as by securing victory through the permanent exclusion or reintegration of the vanquished.
Are dyslexic children involved in delinquency? Issues and recommendations for a more fulfilling life
Authors: Azhar Athirah , Paul Carlo Dolly , Hassan Zamri
Published: November 2022

No dyslexic children are left behind; it takes a village to raise a child. Thus, fostering the achievement potential of dyslexic children and avoiding their engagement in delinquent conduct is none other than everyone’s responsibility. This research aimed to achieve a deeper understanding of the causes of delinquent behaviour in children with dyslexia and to provide solutions that would steer their attitudes and behaviour towards a more ethical and meaningful life. This qualitative study examined three samples representing dyslexic learning centres located in various places. The data were collected through online semi-structured interviews. Following that, the data were analysed utilising thematic analysis. It was discovered children with dyslexia face a variety of challenges. The community’s and parents’ stigma towards these children, such as being slow and lazy, were proven to have influenced them with deviant behaviour. It was recommended that children with learning difficulties get early detection and intervention, have a robust support system and adopt various pedagogical methods to ensure that all students could learn and guarantee dyslexics’ future success. In conclusion, early detection will enable children to get the proper intervention, preventing them from engaging in delinquent behaviours and assisting them in living in a more fulfilling life.
Fly-in-fly-out work: A review of the impact of an extreme form of work-related travel on mental health
Authors: Fruhen Laura S. , Gilbert Jess , Parker Sharon K.
Published: November 2022

Large distances between work and home require many workers to stay away from home for work over extended periods. An extreme case of such work is fly-in-fly-out (FIFO) work. FIFO work requires workers to stay, over a fixed number of days or weeks, in remote employer-arranged accommodation. Given the disruptive nature of this work arrangement, it is important to develop an understanding of its implications for worker mental health. Based on a systematic review, we identify mostly negative mental health implications of FIFO work and propose an integrative model that brings together FIFO work's key features: the simultaneous fracturing and blending of personal and work lives. The model can guide future research. For example, we suggest that researchers investigate how FIFO workers and other work-related travelers experience fracturing and blending, and how they manage the frequent fluctuation between these two extremes.
Supporting Young Children With Disabilities During the COVID-19 Pandemic: Evidence From Caregivers in Virginia
Authors: Shapiro Anna , Bassok Daphna
Published: November 2022

Early care and education (ECE) experiences shape children’s developmental trajectories, particularly for children who have or may have disabilities. However, caregivers of children with disabilities have faced considerable challenges finding care for their children, which have increased during the COVID-19 pandemic. Using survey data from nearly 3,000 caregivers of preschool-age children in Virginia collected in December 2020 and January 2021, we find that caregivers of children with disabilities were less likely to find ECE programs that met their needs, more likely to experience high levels of stress, and more likely to be concerned about their children’s development than were caregivers of children without disabilities. Concerns about child development were particularly pronounced among caregivers of children with disabilities in remote instructional settings. Our findings suggest a disproportionate impact of ECE disruption on caregivers of children with disabilities and the need for targeted supports for these caregivers moving forward.
Evaluation of Transfusion Transmissible Infections Prevalence and Trend Among Blood Donors Attended at Bule Hora Blood Bank, West Guji, South Ethiopia
Authors: Aliyo Alqeer , Ashenafi Girma , Adem Seid
Published: November 2022

Background

Transfusion transmissible infections (TTIs) are among the greatest threats to blood safety for recipients and the economy of the developed and developing countries. Therefore, the study of the prevalence and trends of TTIs is important to assess for its prevention and control strategies.

Objectives

This study aimed to evaluate the prevalence and trend of transfusion transmissible infections among blood donors at the Bule Hora Blood Bank, West Guji, Ethiopia, from 2019 to 2021.

Method

A retrospective study was conducted on all blood donors at the Bule Hora Blood Bank from 2019-2021. The data of 4193 blood donors were collected from the databank (logbook) of the blood bank using a checklist. Data were analyzed by using SPSS software, and the chi-square test was used to assess the association between independent variables and transfusion transmission infection. Different types of graphs, charts and tables were used to present the data. P values less than .05 were considered statistically significant.

Result

The overall transfusion transmissible infection among blood donors was 4.6% (192). Out of the tested blood donors, 86 (2.1%) were found to be seropositive for hepatitis B virus. The trend analysis showed that the positivity rates of the screened tests were 28 (4.72%) in 2019, decreased to 77 (4.26%) in 2020 and increased to 87 (4.86%) in 2021. The sex of blood donors was significantly associated with TTIs ( P value = .021), and the positivity rates were significantly higher among male than female blood donors. The study results showed that overall seropositivity rates increased along the age groups of the donors.

Conclusion

The study reported a moderate prevalence of transfusion transmissible infections among blood donors visiting the Bule hora blood bank. Health education about the transmission, prevention and create awareness of TTIs should be strengthened by the government and non-government organization.
Interventions and outcomes of patients with multiple myeloma receiving salvage therapy after BCMA-directed CAR T therapy
Authors: Van Oekelen Oliver , Nath Karthik , Mouhieddine Tarek H. , Farzana Tasmin , Aleman Adolfo , Melnekoff David T. , Ghodke-Puranik Yogita , Shah Gunjan L. , Lesokhin Alexander , Giralt Sergio , Thibaud Santiago , Rossi Adriana , Rodriguez Cesar , Sanchez Larysa , Richter Joshua , Richard Shambavi , Cho Hearn J. , Chari Ajai , Usmani Saad Z. , Jagannath Sundar , Shah Urvi A. , Mailankody Sham , Parekh Samir
Published: November 2022

B-cell maturation antigen (BCMA)–directed chimeric antigen receptor T-cell (CAR T) therapy has demonstrated remarkable efficacy in patients with relapsed/refractory multiple myeloma, and now there are two US Food and Drug Administration–approved BCMA-directed CAR T products. However, despite high initial response rates, most patients eventually relapse. The outcomes of patients with disease recurrence after BCMA-directed CAR T have not been comprehensively studied, and such an analysis would help define optimal treatment strategies. We analyzed the salvage treatments and outcomes of 79 patients with multiple myeloma from two academic institutions, who had progression of disease after treatment with BCMA-directed CAR T. A total of 237 post–CAR T salvage treatment lines were used, and patients received a median of 2 (range, 1-10) treatment lines. The median overall survival from the date of relapse post-CAR T therapy was 17.9 months (95% confidence interval [CI], 14.0 non-estimable). The overall response rate to the first salvage regimen was 43.4%, with a median progression-free survival of 3.5 months (CI, 2.5-4.6). Thirty-five patients (44.3%) received a T-cell–engaging therapy (bispecific antibody or subsequent CAR T) as salvage treatment. The overall survival in patients who received subsequent T-cell–engaging therapy was not reached after a median follow up of 21.3 months. Patients with multiple myeloma who relapse after BCMA-directed CAR T have a limited prognosis but can be potentially treated with multiple lines of salvage therapy. T-cell–engaging therapies appear to maintain pronounced clinical activity in this setting.
Identifying optimal candidates for postoperative adjuvant therapy among regional persistent/recurrent nasopharyngeal carcinoma patients after neck dissection
Authors: Liu Sai-Lan , Li Xiao-Yun , Sun Xue-Song , Peng Jing-Yun , Lin Chao , Yan Jin-Jie , Chen Qiu-Yan , Tang Lin-Quan , Guo Shan-Shan , Guo Ling , Liu Li-Ting , Mai Hai-Qiang
Published: November 2022

Purpose

To analyze the clinical outcomes of patients with regional persistent/recurrent nasopharyngeal carcinoma (NPC) who received neck dissection, and to evaluate the clinical benefit of postoperative adjuvant therapy (PAT) based on patients’ positive lymph node counts (PLNs), extracapsular spread (ECS) and preoperative plasma EBV DNA levels.

Methods

From 2003 to 2017, 342 patients with regional persistent/recurrent NPC were included in this study. All patients were treated with neck dissection and 76 patients received PAT. Progression-free survival (PFS), overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRFS) were compared between groups using propensity score matching (PSM).

Results

152 patients without PAT treatment and 76 patients with PAT treatment were selected by the PSM. There was no significant difference in 2-year PFS (52.4% vs. 61.3%, P = 0.371), 2-year OS (91.9% vs. 90.5%, P = 0.097) or 2-year LRFS (66.3% vs. 67.9%, P = 0.872) between the two groups. However, the application of PAT brought survival benefits to patients in terms of 2-year DMFS (76.5% vs. 84.7%, P = 0.020). PLN, ECS and preoperative EBV DNA level remained independent risk factors for poorer PFS. Accordingly, patients were divided into low-risk and high-risk groups using receiver operating characteristic (ROC) curve; the 2-year PFS rates for two risk groups were 73.4% and 59.1% (P < 0.0001) respectively. The results showed that low-risk patients didn’t benefit from the addition of PAT. However, the 2-year DMFS rate was significantly improved in high-risk PAT-treated patients than those treated by neck dissection alone (83.7% vs. 71.7%, P = 0.023).

Conclusions

PLNs, ECS and preoperative EBV DNA level are associated with the prognosis of patients with regional persistent/recurrent NPC. High-risk patients identified by PLNs, ECS and preoperative EBV DNA level may benefit from the addition of PAT after neck dissection.
Effects of the Omicron variant on perinatal outcomes in full-term neonates
Authors: Choi Hyowon , Lee Eun Jung , Ahn Yeon-Soon , Yoo Yeong Myong
Published: November 2022

Background

Research of coronavirus disease (COVID-19) effects on newborns is ongoing. But the research of specific variant’s effects is none. This study analyzed the effects of the Omicron variant on the perinatal outcomes of full-term newborns during the Omicron wave period. 

Methods

Between December 2021 and April 2022, this study was conducted on all newborns who visited a single center. We investigated due to the Omicron maternal infection maternal pregnancy complications, delivery methods, birth week, Apgar scores, neonatal resuscitation program requirement, whether respiratory support was required until 12 h after childbirth, suspicious infectious status, and mortality depending on maternal Omicron infection.

Results

A total of 127 neonates were enrolled, and 12 were excluded based on exclusion criteria. Sixteen neonates were born to mothers with a history of Omicron COVID-19, and 99 were born to non-infectious mothers. All infected mothers became infected in the 3rd trimester. Of the 16 mothers, seven were symptomatic, and four met the isolation criteria, according to Korean guidelines. The birth weight of newborns to mothers with a history of COVID and those without was 2.958 ± 0.272 kg and 3.064 ± 0.461 kg (p = 0.049), respectively. The 5-min Apgar score at childbirth was 9.29 ± 0.756 and 9.78 ± 0.460 for neonates born to symptomatic and asymptomatic mothers (p = 0.019), respectively. When compared with or without maternal self-isolation, neonates requiring respiratory support 12 h after birth demonstrated a significant difference (p = 0.014; OR, 10.275). Additionally, the presence or absence of transient tachypnea of the newborn showed a significant value (p = 0.010; OR 11.929).

Conclusions

Owing to Omicron COVID-19, newborns were born with lower birth weight, low 5-min Apgar scores, and required respiratory support until 12 h after birth.
Lower gestational age is associated with lower cortical volume and cognitive and educational performance in adolescence
Authors: Ma Qing , Wang Hui , Rolls Edmund T. , Xiang Shitong , Li Jiong , Li Yuzhu , Zhou Qiongjie , Cheng Wei , Li Fei
Published: November 2022

Background

Gestational age (GA) is associated with later cognition and behavior. However, it is unclear how specific cognitive domains and brain structural development varies with the stepwise change of gestational duration.

Methods

This large-scale longitudinal cohort study analyzed 11,878 early adolescents’ brain volume maps at 9–10 years (baseline) and 5685 at 11–12 years (a 2-year follow-up) from the Adolescent Brain Cognitive Development (ABCD) study. According to gestational age, adolescents were divided into five categorical groups: ≤ 33 weeks, 34–35 weeks, 36 weeks, 37–39 weeks, and ≥ 40 weeks. The NIH Toolbox was used to estimate neurocognitive performance, including crystallized and fluid intelligence, which was measured for 11,878 adolescents at baseline with crystallized intelligence and relevant subscales obtained at 2-year follow-up (with participant numbers ranging from 6185 to 6310 depending on the cognitive domain). An additional large population-based cohort of 618,070 middle adolescents at ninth-grade (15–16 years) from the Danish national register was utilized to validate the association between gestational age and academic achievements. A linear mixed model was used to examine the group differences between gestational age and neurocognitive performance, school achievements, and grey matter volume. A mediation analysis was performed to examine whether brain structural volumes mediated the association between GA and neurocognition, followed with a longitudinal analysis to track the changes.

Results

Significant group differences were found in all neurocognitive scores, school achievements, and twenty-five cortical regional volumes (P < 0.05, Bonferroni corrected). Specifically, lower gestational ages were associated with graded lower cognition and school achievements and with smaller brain volumes of the fronto-parieto-temporal, fusiform, cingulate, insula, postcentral, hippocampal, thalamic, and pallidal regions. These lower brain volumes mediated the association between gestational age and cognitive function (P = 1 × 10−8, β = 0.017, 95% CI: 0.007–0.028). Longitudinal analysis showed that compared to full term adolescents, preterm adolescents still had smaller brain volumes and crystallized intelligence scores at 11–12 years.

Conclusions

These results emphasize the relationships between gestational age at birth and adolescents’ lower brain volume, and lower cognitive and educational performance, measured many years later when 9–10 and 11–12 years old. The study indicates the importance of early screening and close follow-up for neurocognitive and behavioral development for children and adolescents born with gestational ages that are even a little lower than full term.
A feline case of multiple myeloma treated with bortezomib
Authors: Tani Hiroyuki , Miyamoto Ryo , Miyazaki Teruki , Oniki Shingo , Tamura Kyoichi , Bonkobara Makoto
Published: November 2022

Background

Multiple myeloma (MM) is an uncommon neoplasm in cats. There is no established standard of treatment due to the rare occurrence of this disease in cats. Bortezomib is a proteasome inhibitor that serves as the first-line drug for MM in humans, but its effectiveness currently is unknown in feline MM. We present here the case report of a feline MM that exhibited a favorable response to bortezomib.

Case presentation

The case was an 11-year-old non-castrated male domestic cat with light-chain MM presenting with clinical symptoms (anorexia, fatigue, and vomiting), mild azotemia, and pancytopenia. The cat failed on melphalan with prednisolone (MP), so bortezomib (Velcade) was initiated on Day 88. A total of 6 cycles of the treatment was performed, with each treatment cycle consisting of twice-weekly subcutaneous administration for 2 weeks followed by a 1-week rest. The dose of bortezomib was 0.7 mg/m2 for first week and 1.0 mg/m2 for second week in the first cycle. A dose of 0.7 mg/m2 was used for subsequent cycles. Prednisolone was used concomitantly in the first 2 cycles. Following treatment with bortezomib, clinical symptoms disappeared and a decrease in serum globulin and recovery of pancytopenia were noted. A monoclonal gammopathy, overproduction of serum immunoglobulin light chain, and Bence-Jones proteinuria that existed at diagnosis were undetectable on Day 123. A monoclonal gammopathy also was not detectable at the end of the bortezomib treatment (Day 213). Anorexia, fatigue, and marked bone marrow toxicity were experienced when bortezomib was administrated at a dose of 1.0 mg/m2, while no recognizable toxicity was observed at a dose of 0.7 mg/m2 throughout the treatment period. The case was placed on follow-up and there was no evidence of relapse as of Day 243.

Conclusions

Bortezomib was effective and durable for the treatment of this case of feline MM after failure with MP. Bortezomib was well-tolerated in this cat at a dose of 0.7 mg/m2, but not at 1.0 mg/m2. Bortezomib appears to be a drug worthy of further study for the treatment of feline MM.
Dual-targeting nanozyme for tumor activatable photo-chemodynamic theranostics
Authors: Chen Chaoyi , Chen Yuwen , Zhang Lulu , Wang Xuanhao , Tang Qingshuang , Luo Yan , Wang Yuan , Ma Cheng , Liang Xiaolong
Published: November 2022

Tumor phototheranostics holds a great promise on account of its high spatiotemporal resolution, tumor-specificity, and noninvasiveness. However, physical limitation of light penetration and “always on” properties of conventional photothermal-conversion agents usually cause difficulty in accurate diagnosis and completely elimination of tumor. Meanwhile, nanozymes mediated Fenton reactions can well utilize the tumor microenvironment (TME) to generate hydroxyl radicals for chemodynamic therapy (CDT), but limited by the concentration of H2O2 in TME and the delivery efficiency of nanozymes. To overcome these problems, a dual-targeting nanozyme (FTRNPs) is developed for tumor-specific in situ theranostics, based upon the assembling of ultrasmall Fe3O4 nanoparticles, 3,3’,5,5’-tetrameth-ylbenzidine (TMB) and the RGD peptide. The FTRNPs after H2O2 treatment exhibits superior photothermal stability and high photothermal conversion efficiency (η = 50.9%). FTRNPs shows extraordinary accumulation and retention in the tumor site by biological/physical dual-targeting, which is 3.54-fold higher than that without active targeting. Cascade-dual-response to TME for nanozymes mediated Fenton reactions and TMB oxidation further improves the accuracy of both photoacoustic imaging and photothermal therapy (PTT). The tumor inhibition rate of photo-chemodynamic therapy is ~ 97.76%, which is ~ 4-fold higher than that of PTT or CDT only. Thus, the combination of CDT and PTT to construct “turn on” nanoplatform is of great significance to overcome their respective limitations. Considering its optimized “all-in-one” performance, this new nanoplatform is expected to provide an advanced theranostic strategy for the future treatment of cancers.

Graphical abstract
Scalable and high-throughput production of an injectable platelet-rich plasma (PRP)/cell-laden microcarrier/hydrogel composite system for hair follicle tissue engineering
Authors: Zhang Yufan , Yin Panjing , Huang Junfei , Yang Lunan , Liu Zhen , Fu Danlan , Hu Zhiqi , Huang Wenhua , Miao Yong
Published: November 2022

Background

Tissue engineering of hair follicles (HFs) has enormous potential for hair loss treatment. However, certain challenges remain, including weakening of the dermal papilla cell (DPC) viability, proliferation, and HF inducibility, as well as the associated inefficient and tedious preparation process required to generate extracellular matrix (ECM)-mimicking substrates for biomolecules or cells. Herein, we utilized gelatin methacryloyl (GelMA) and chitosan hydrogels to prepare scalable, monodispersed, and diameter-controllable interpenetrating network GelMA/chitosan-microcarriers (IGMs) loaded with platelet-rich plasma (PRP) and seeded with DPCs, on a high-throughput microfluidic chip.

Results

The ECM-mimicking hydrogels used for IGMs exhibited surface nano-topography and high porosity. Mass production of IGMs with distinct and precise diameters was achieved by adjusting the oil and aqueous phase flow rate ratio. Moreover, IGMs exhibited appropriate swelling and sustained growth factor release to facilitate a relatively long hair growth phase. DPCs seeded on PRP-loaded IGMs exhibited good viability (> 90%), adhesion, spreading, and proliferative properties (1.2-fold greater than control group). Importantly, PRP-loaded IGMs presented a higher hair inducibility of DPCs in vitro compared to the control and IGMs group (p < 0.05). Furthermore, DPC/PRP-laden IGMs were effectively mixed with epidermal cell (EPC)-laden GelMA to form a PRP-loaded DPC/EPC co-cultured hydrogel system (DECHS), which was subcutaneously injected into the hypodermis of nude mice. The PRP-loaded DECHS generated significantly more HFs (~ 35 per site) and novel vessels (~ 12 per site) than the other groups (p < 0.05 for each).

Conclusion

Taken together, these results illustrate that, based on high-throughput microfluidics, we obtained scalable and controllable production of ECM-mimicking IGMs and DECHS, which simulate an effective micro- and macro-environment to promote DPC bioactivity and hair regeneration, thus representing a potential new strategy for HF tissue engineering.
Assessing the genetic burden of familial hypercholesterolemia in a large middle eastern biobank
Authors: Gandhi Geethanjali Devadoss , Aamer Waleed , Krishnamoorthy Navaneethakrishnan , Syed Najeeb , Aliyev Elbay , Al-Maraghi Aljazi , Kohailan Muhammad , Alenbawi Jamil , Elanbari Mohammed ,   Qatar Genome Program Research Consortium (QGPRC), Mifsud Borbala , Mokrab Younes , Abi Khalil Charbel , Fakhro Khalid A.
Published: November 2022

Background

The genetic architecture underlying Familial Hypercholesterolemia (FH) in Middle Eastern Arabs is yet to be fully described, and approaches to assess this from population-wide biobanks are important for public health planning and personalized medicine.

Methods

We evaluate the pilot phase cohort (n = 6,140 adults) of the Qatar Biobank (QBB) for FH using the Dutch Lipid Clinic Network (DLCN) criteria, followed by an in-depth characterization of all genetic alleles in known dominant (LDLR,APOB, andPCSK9) and recessive (LDLRAP1,ABCG5,ABCG8, andLIPA) FH-causing genes derived from whole-genome sequencing (WGS). We also investigate the utility of a globally established 12-SNP polygenic risk score to predict FH individuals in this cohort with Arab ancestry.

Results

Using DLCN criteria, we identify eight (0.1%) ‘definite’, 41 (0.7%) ‘probable’ and 334 (5.4%) ‘possible’ FH individuals, estimating a prevalence of ‘definite or probable’ FH in the Qatari cohort of ~ 1:125. We identify ten previously known pathogenic single-nucleotide variants (SNVs) and 14 putatively novel SNVs, as well as one novel copy number variant inPCSK9. Further, despite the modest sample size, we identify one homozygote for a known pathogenic variant (ABCG8, p. Gly574Arg, global MAF = 4.49E-05) associated with Sitosterolemia 2. Finally, calculation of polygenic risk scores found that individuals with ‘definite or probable’ FH have a significantly higher LDL-C SNP score than ‘unlikely’ individuals (p = 0.0003), demonstrating its utility in Arab populations.

Conclusion

We design and implement a standardized approach to phenotyping a population biobank for FH risk followed by systematically identifying known variants and assessing putative novel variants contributing to FH burden in Qatar. Our results motivate similar studies in population-level biobanks – especially those with globally under-represented ancestries – and highlight the importance of genetic screening programs for early detection and management of individuals with high FH risk in health systems.
Apparent mineralocorticoid excess: comprehensive overview of molecular genetics
Authors: Lu Yi-ting , Zhang Di , Zhang Qiong-yu , Zhou Ze-ming , Yang Kun-qi , Zhou Xian-liang , Peng Fan
Published: November 2022

Apparent mineralocorticoid excess is an autosomal recessive form of monogenic disease characterized by juvenile resistant low-renin hypertension, marked hypokalemic alkalosis, low aldosterone levels, and high ratios of cortisol to cortisone metabolites. It is caused by defects in theHSD11B2gene, encoding the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which is primarily involved in the peripheral conversion of cortisol to cortisone. To date, over 50 deleteriousHSD11B2mutations have been identified worldwide. Multiple molecular mechanisms function in the lowering of 11β-HSD2 activity, including damaging protein stability, lowered affinity for the substrate and cofactor, and disrupting the dimer interface. Genetic polymorphism, environmental factors as well as epigenetic modifications may also offer an implicit explanation for the molecular pathogenesis of AME. A precise diagnosis depends on genetic testing, which allows for early and specific management to avoid the morbidity and mortality from target organ damage. In this review, we provide insights into the molecular genetics of classic and non-classic apparent mineralocorticoid excess and aim to offer a comprehensive overview of this monogenic disease.
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

Background

Periodontitis 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.

Methods

Using 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.

Results

We 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.

Conclusion

These 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

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

Background

Previous 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.

Objective

We 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.

Methods

A 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.

Results

A 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.

Conclusion

Here, 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

Background

Service 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.

Methods

This 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.

Conclusion

Current 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

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

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

Metachromatic 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.