bluuebunny/crossref_metadata_2025_split huggingface dataset:
Generation and transplantation of hepatocytes‐like cells using human origin hepatogenic serum for acute liver injury treatment
Authors: Gupta Santosh , Sharma Akriti , Paneerselvan Sugan , Kandoi Sangeetha , Patra Bamadeb , Bishi Dillip Kumar , Verma Rama Shanker 
Published: February 2022

AbstractLiver failure is a critical disease for which regenerative therapies are still being explored. The major limitation in the use of a clinical grade, viable cell‐based therapy approach is the scarce availability of sufficient number of in‐vitro differentiated hepatocyte‐like cells (HLC) that can induce regeneration and ameliorate liver injury. Here, we report for the first time an approach to engineer HLCs using sera of hyperbilirubin patients that act as a reservoir of differentiation factor. Utilizing our humanized approach, mesenchymal stem cells (hMSC) derived from umbilical cord tissue were transdifferentiated into HLC using patient‐derived serum along with dimethyl sulfoxide (DMSO). We studied the effects of serum on the proliferation, cell cycle analysis, and apoptosis of hMSC by various differentiation combinations. We optimized the hepatic transdifferentiation ability of hMSC with hyperbilirubin serum treatment for a period of 7 days. Assessment of HLC functionalities was shown by quantifying the HLC spent medium for albumin and urea secretions. Transplantation of HLC in an acute liver injury (ALI) rat model showed an effective improvement in the liver function and histological changes in the liver. The results of this study suggest that hMSC‐derived HLC using humanized hepatogenic serum holds a promising potential for cell transplantation, as an efficient therapy modality for liver failure in humans.
hEPCR.hTBM.hCD47.hHO‐1 with donor clodronate and DDAVP treatment improves perfusion and function of GalTKO.hCD46 porcine livers perfused with human blood
Authors: Cimeno Arielle , Kuravi Kasinath , Sorrells Lori , Dandro Amy , Sendil Selin , Burdorf Lars , Parsell Dawn M. , Eyestone Will , Phelps Carol , Ayares David , Azimzadeh Agnes M. , Pierson Richard N. , Barth Rolf N. , LaMattina John C. 
Published: February 2022

AbstractIntroductionPlatelet sequestration, inflammation, and inappropriate coagulation cascade activation are prominent in liver xenotransplant models and are associated with poor outcomes. Here, we evaluate a cassette of six additional genetic modifications to reduce anti‐pig antibody binding (α‐1,3‐galactosyl transferase knockout [GalTKO]) and target coagulation dysregulation (human endothelial protein C receptor [hEPRC] and thrombomodulin [hTBM]), complement pathway regulation (human membrane cofactor protein, hCD46), inflammation heme oxygenase 1 [hHO‐1]), and a self‐recognition receptor (integrin‐associated protein [hCD47]), as well as donor pharmacologic treatments designed to blunt these phenomena.MethodsLivers from GaltKO.hCD46 pigs (“2‐gene,” n = 3) and GalTKO.hCD46 pigs also transgenic for hEPRC, hTBM, hCD47, and hHO‐1 (“6‐gene,” n = 4) were perfused ex vivo with whole human blood. Six‐gene pigs were additionally pretreated with desmopressin (DDAVP) and clodronate liposomes to deplete vWF and kupffer cells, respectively.ResultsThe average perfusion times increased from 304 (±148) min in the 2‐gene group to 856 (±61) min in the 6‐gene group (p = .010). The average heparin administration was decreased from 8837 U/h in the 2‐gene to 1354 U/h in the 6‐gene group (p = .047). Platelet sequestration tended to be delayed in the 6‐gene group (p = .070), while thromboxane B2 (TXB2, a platelet activation marker) levels were lower over the first hour (p = .044) (401 ± 124 vs. 2048 ± 712 at 60 min). Thrombin production as measured by F1+2 levels tended to be lower in the 6‐gene group (p = .058).ConclusionsThe combination of the hEPCR.hTBM.hCD47.hHO‐1 cassette along with donor pig DDAVP and clodronate liposome pretreatment was associated with prolonged function of xenoperfused livers, reduced coagulation pathway perturbations, and decreased TXB2 elaboration, and reflects significant progress to modulate liver xenograft injury in a pig to human model.
Frequency‐dependent characteristics of nerve‐mediated ATP and acetylcholine release from detrusor smooth muscle
Authors: Chakrabarty Basu , Aitchison Katie , White Paul , McCarthy Carly J. , Kanai Anthony J. , Fry Christopher H. 
Published: February 2022

New Findings

What is the central question of this study?
Is the frequency dependence of co‐transmitter release from postganglionic nerve fibres different for each transmitter?

What is the main finding and its importance?
Release of co‐transmitters from the parasympathetic supply to detrusor smooth muscle can be independently regulated. This offers a targeted drug model to reduce selectively the release of transmitter associated with human pathologies (ATP) and may also be applicable to other smooth muscle‐based disorders of visceral tissues.

AbstractNerve‐mediated contractions of detrusor smooth muscle are mediated by acetylcholine (ACh) and ATP release in most animals. However, with the normal human bladder, only ACh is a functional transmitter, but in benign pathologies such as overactive bladder (OAB), ATP re‐emerges as a secondary transmitter. The selective regulation of ATP release offers a therapeutic approach to manage OAB, in contrast to current primary strategies that target ACh actions. However, the release characteristics of nerve‐mediated ACh and ATP are poorly defined and this study aimed to measure the frequency dependence of ACh and ATP release and determine if selective regulation of ATP or ACh was possible. Experiments were carried out in vitro with mouse detrusor with nerve‐mediated ATP and ACh release measured simultaneously with tension recording. ATP was released in two frequency‐dependent components, both at lower frequencies (mid‐range 0.4 and 5.5 Hz stimulation) compared to a single compartment release of ACh at 14 Hz. Intervention with the phosphodiesterase type‐5 inhibitor sildenafil attenuated ATP release, equally from both components, but had no effect on ACh release. These data demonstrate that nerve‐mediated ACh and ATP release characteristics are distinct and may be separately manipulated. This offers a potential targeted drug model to manage benign lower urinary tract conditions such as OAB.
Strengthening research capacity: a systematic review of manuscript writing and publishing interventions for researchers in low-income and middle-income countries
Authors: Busse Clara E , Anderson Elizabeth W , Endale Tamrat , Smith Yolanda Regina , Kaniecki Marie , Shannon Carol , August Ella T 
Published: February 2022

IntroductionHealth researchers from low-income and middle-income countries (LMICs) are under-represented in the academic literature. Scientific writing and publishing interventions may help researchers publish their findings; however, we lack evidence about the prevalence and effectiveness of such interventions. This review describes interventions for researchers in LMICs aimed at strengthening capacity for writing and publishing academic journal articles.MethodsWe followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to report literature searches in PubMed, Embase, Global Health, Scopus and ERIC. Our keywords included LMICs, low-income and middle-income countries, health research and writing/publication support interventions, with no restrictions on publication date. Our screening process consisted of title screening, abstract review and full-text review. We collected information about the content, implementation and evaluation of each intervention, if included.ResultsWe identified 20 interventions designed to strengthen capacity for scientific writing and publishing. We summarised information from the 14 interventions that reported submitted or published papers as outcomes separately, reasoning that because they provide quantifiable metrics of success, they may offer particular insights into intervention components leading to publication. The writing and publishing components in this ‘Publications Reported’ group were an average length of 5.4 days compared with 2.5 days in the other group we refer to as ‘Other Interventions.’ Whereas all 14 Publications Reported interventions incorporated mentors, only two of five in the Other Interventions group incorporated mentors. Across interventions, leaders expressed the importance of a high ratio of mentors to participants, the need to accommodate time demands of busy researchers, and the necessity of a budget for open access fees and high-quality internet connectivity.ConclusionWriting and publishing interventions in LMICs are an underutilised opportunity for capacity strengthening. To facilitate the implementation of high-quality interventions, future writing and publishing interventions should share their experiences by publishing detailed information about the approach and effectiveness of the interventions.
Experiences of pain in paediatric chronic fatigue syndrome/myalgic encephalomyelitis: a single-centre qualitative study
Authors: Serafimova Teona , Ascough Caitlin , Parslow Roxanne Morin , Crawley Esther 
Published: February 2022

BackgroundModerate to severe pain affects up to two-thirds of children with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and is associated with worse fatigue and physical functioning. This research aims to gain a greater insight into pain experienced by these children.MethodsThematic analysis of qualitative data from semistructured interviews with 13 children with CFS/ME (mean age=15.3 years, 67% female) was completed.ResultsThematic analysis enabled construction of three themes: children’s wide-ranging experiences of pain, negative impact of pain and lack of effective treatment for pain and nine subthemes. The first theme demonstrated highly varied pain experiences, ranging from ‘like [being]… on fire’, like ‘being stabbed’ to ‘like…lead’. Children experienced pain in multiple sites and with wide-ranging frequency and severity. The second theme highlighted the profound negative impact of pain on multiple aspects of children’s lives. Physical activity was severely impaired; some children ‘couldn’t leave bed’ or ‘couldn’t…brush [their] own hair’. Abdominal pain meant some would ‘go…days without eating’. Pain substantially impacted on mental health, leaving children feeling ‘agitated’, experiencing ‘really bad panic attacks’ or making them ‘[want to] breakdown’. Children felt they ‘can’t do the things that everyone else can do’, had ‘missed out’ and are ‘behind everyone’. Some avoided socialising as they ‘don’t want to stop everyone else’. The final theme demonstrates the absence of adequate treatment for pain, with participants reporting ‘nothing has ever really got rid of it’ and only ‘slightly [takes] the edge off’ and other experiencing side effects.ConclusionsPain in paediatric CFS/ME is highly variable, common and often results in severe physical limitation and poor mental health. Effective treatments for pain represent an unmet need.
Muscle-Strengthening Exercise Questionnaire (MSEQ): an assessment of concurrent validity and test–retest reliability
Authors: Shakespear-Druery Jane , De Cocker Katrien , Biddle Stuart J H , Bennie Jason 
Published: February 2022

ObjectivesMuscle-strengthening exercise (MSE) has multiple independent health benefits and is a component of global physical activity guidelines. However, the assessment of MSE in health surveillance is often limited to the constructs of frequency (days/week), with little focus on constructs such as MSE type, muscle groups targeted and intensity. This study describes the test–retest reliability and concurrent validity of the Muscle-Strengthening Exercise Questionnaire (MSEQ), which was developed to assess multiple MSE participation constructs.MethodsThe MSEQ was developed to assess the weekly frequency, session duration and intensity, types of MSE (eg, weight machines, bodyweight exercise) and muscle groups targeted. Two convenience samples of adult participants were recruited. Test–retest reliability was completed online by 85 participants. Concurrent validity was assessed for 54 participants using an online 7-day MSE log.ResultsThe MSEQ shows high test–retest reliability for frequency, duration and level of intensity for each of the four MSE types (using weight machines, bodyweight exercises, resistance exercises and holistic exercises), and for the four types combined (ρ range 0.76–0.91). For muscle groups targeted, the reliability ranged mostly from moderate-to-substantial for each of the four MSE types (κ range 0.44–0.78) and fair-to-moderate for the four types combined (κ range 0.35–0.51). Concurrent validity for frequency, duration and level of intensity for each of the four MSE types, and the four types combined, was moderate-to-high (ρ range 0.30–0.77).ConclusionThe MSEQ shows acceptable reliability and validity for four key MSE constructs. This new MSEQ survey instrument could be used to assess adults’ MSE.
Iberdomide in patients with systemic lupus erythematosus: a randomised, double-blind, placebo-controlled, ascending-dose, phase 2a study
Authors: Furie Richard A , Hough Douglas R , Gaudy Allison , Ye Ying , Korish Shimon , Delev Nikolay , Weiswasser Michael , Zhan Xiaojiang , Schafer Peter H , Werth Victoria P 
Published: February 2022

ObjectiveTo evaluate safety, pharmacokinetics, pharmacodynamics and efficacy of iberdomide in patients with SLE. Iberdomide is a high-affinity cereblon ligand that targets the hematopoietic transcription factors Ikaros and Aiolos for proteasomal degradation.MethodsA 12-week, multicentre, double-blind, placebo-controlled, dose-escalation study in active SLE was followed by a 2-year, open-label active treatment extension phase (ATEP) (NCT02185040). In the dose-escalation phase, adults with active SLE were randomised to oral placebo or iberdomide (0.3 mg every other day, 0.3 mg once daily, 0.6 mg and 0.3 mg alternating once daily, or 0.6 mg once daily). Primary endpoints were safety and tolerability.ResultsThe dose-escalation phase enrolled 42 patients, with 33 completing this phase and 17 patients enrolling into the ATEP. In the dose-escalation phase, the most common treatment-emergent adverse events (TEAEs; iberdomide/placebo groups) were nausea (20.6%/12.5%), diarrhoea (17.6%/12.5%) and upper respiratory tract infection (11.8%/12.5%). Most TEAEs were mild or moderate in severity and more common in the highest dose groups in both study phases. In the dose-escalation phase, Physician’s Global Assessment and Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) activity scores improved relative to baseline and placebo in all iberdomide groups, with a trend toward continued score improvements in the ATEP. In the dose-escalation phase, iberdomide treatment resulted in dose-dependent reductions in total B cells and plasmacytoid dendritic cells in blood. Improvements in CLASI activity scores correlated with plasmacytoid dendritic cell depletion.ConclusionsThese proof-of-concept findings suggest a favourable benefit/risk ratio in SLE for iberdomide, a drug with a novel immunomodulatory mechanism of action, supporting further clinical investigation.
Ropivacaine-loaded, hydroxypropyl chitin thermo-sensitive hydrogel combined with hyaluronan: an injectable, sustained-release system for providing long-lasting local anesthesia in rats
Authors: Qiao Qianqian , Fu Xiangyun , Huang Rui , Lei Shaoqing , Leng Yan , Liu Zhigang , Xia Zhongyuan , Jiang Xulin 
Published: February 2022

Background and objectiveRopivacaine hydrochloride is a commonly used local anesthetic in clinics. However, local injection or continuous infusion of ropivacaine has been associated with several disadvantages. Accordingly, it is important to develop a new controlled release system for local administration of ropivacaine to achieve a prolong anesthetic effect, improve efficacy, and minimize the side effects.MethodsWe developed injectable hydroxypropyl chitin thermo-sensitive hydrogel (HPCH) combined with hyaluronan (HA), which was used to synthesize a ropivacaine (R)-loaded controlled release system. We then conducted drug release test and cytotoxicity assay in vitro. Importantly, we examined the analgesic effects and biocompatibility of this system in vivo by injecting different concentrations of R-HPCH-HA (7.5, 15, 22.5 mg/mL), ropivacaine hydrochloride (RHCL, 7.5 mg/mL), or saline (all in 0.5 mL) near the sciatic nerve in rats.ResultsR-HPCH-HA induced concentration-dependent thermal-sensory blockade and motor blockade in vivo. In hot plate test, R-HPCH-HA (22.5 mg/mL) induced a significant longer thermal-sensory blockade (17.7±0.7 hours), as compared with RHCL(7.5 mg/mL, 5.7±0.8 hours, n=6/group, p<0.05). It also produced a more prolonged motor blockade (6.8±0.8 hours) than RHCL(3.5±0.8 hours, p<0.05). R-HPCH-HA caused less cytotoxicity than RHCL, as indicated by the higher cell viability in vitro (n=8/group).ConclusionOur findings in a sciatic nerve block model demonstrated that the injectable, ropivacaine-loaded controlled release system effectively prolonged the local analgesic effect in rats without notable side effects.
Association between fetal famine exposure and risk of type 2 diabetes: a prospective cohort study
Authors: Wang Cun , Luo Xiaoyan , Tao Boni , Du Wei , Hou Liying , Chen Shuohua , Yang Peng , Wu Shouling , Li Yun 
Published: February 2022

The objective of this study was to explore the effects of fetal experience of famine on the onset of type 2 diabetes mellitus (T2DM) in adults. The analysis included 16 594 participants from the Kailuan Study who were free of diabetes at baseline (2006). According to the date of birth, the individuals born on October 1, 1962 – September 30, 1964, were divided into the non-exposed group (used as the reference group), individuals born on October 1, 1959 – September 30, 1961, were divided into the fetal exposure group, and the early childhood exposure group included those born on October 1, 1956 – September 30, 1958. The cumulative incidence of T2DM for each group was calculated and compared among the 3 groups, and the Cox regression model was used to analyze the effects of fetal famine experience on the risk of diabetes. During a median 10.27 years (170 358 person-years) (2006–2017), 3509 incident T2DM cases were identified, with a cumulative incidence rate of 19.46%. The cumulative incidences of T2DM in the non-exposed, fetal exposure, and early childhood exposure groups were 17.38%, 20.85%, and 20.65%, respectively (P < 0.01). After adjusting for confounding factors, the hazard ratio (HR) of T2DM in the fetal exposure group was 1.222 (95% confidence interval: 1.087–1.374, P < 0.01), compared with the reference group. The association was modified by sex and hypertension (both P interaction less than 0.05). Fetal famine exposure may increase the risk of developing T2DM in adults. This association was more pronounced among women and those with hypertension. Novelty: The association was modified by sex and hypertension. Long follow-up time.
Tidal deformation and radial pulsations of neutron star with holographic multiquark core
Authors: Pinkanjanarod Sitthichai , Burikham Piyabut , Ponglertsakul Supakchai 
Published: February 2022

AbstractTidal deformation of neutron star with multiquark core is calculated using nuclear and multiquark equations of state. The equation of state of the multiquark phase from the holographic Sakai-Sugimoto (SS) model is relatively stiff in the low density region and becomes softer at high densities. The values of Love number and dimensionless deformation parameter, $$k_{2}$$

k
2

and $$\Lambda $$
Λ
, are found to be within the physically viable range under the present constraints. Radial pulsation frequencies of the multiquark core for $$n=0-5$$

n
=
0
-
5

modes are calculated for the entire mass range. For $$M_{\mathrm{core}}\simeq 2 M_{\odot }$$

M
core

≃
2

M
⊙

, the fundamental-mode frequency is approximately 2.5 kHz for the energy density scale $$\epsilon _{s}=23.2037$$

ϵ
s

=
23.2037

GeV/fm$$^{3}$$

3

of the holographic SS model, this frequency is proportional to $$\sqrt{\epsilon _{s}}$$

ϵ
s

.
A Classification Tree Model with Optical Coherence Tomography Angiography Variables to Screen Early-Stage Diabetic Retinopathy in Diabetic Patients
Authors: Yao Hongyan , Wu Shanjun , Zhan Zongyi , Li Zijing 
Published: February 2022

Aim. To establish a classification tree model in DR screening and to compare the DR screening accuracy between the classification tree model and the logistic regression model in type 2 diabetes mellitus (T2DM) patients based on OCTA variables. Methods. Two hundred forty-one eyes of 241 T2DM patients were included and divided into two groups: the development cohort and the validation cohort. Optical coherence tomography angiography (OCTA) images were acquired in these patients. The data of foveal avascular zone area, superficial capillary plexus (SCP) density, and deep capillary plexus (DCP) density were exported after automatically analyzing the macular 6 × 6 mm OCTA images, while the data of radial peripapillary capillary plexus (RPCP) density was exported after automatically analyzing the optic nerve head 4.5 × 4.5 mm OCTA images. These OCTA variables were adopted to establish and validate the logistic regression model and the classification tree model. The area under the curve (AUC), sensitivity, specificity, and statistical power for receiver operating characteristic curves of two models were calculated. Results. In the logistic regression model, best-corrected visual acuity (BCVA) (LogMAR) and SCP density were entered (BVCA : OR= 60.30, 95% CI= [2.40, 1513.82],

p

= 0.013; SCP density: OR= 0.86, 95% CI= [0.78, 0.96],

p

= 0.006). The AUC, sensitivity, and specificity for detecting early-stage DR (mild to moderate NPDR) in the development cohort were 0.75 (95% CI: [0.66, 0.85]), 63%, and 83%, respectively. The AUC, sensitivity, and specificity in the validation cohort were 0.75 (95% CI: [0.66, 0.84]), 79%, and 72%, respectively. In the classification tree model, BVCA (LogMAR), DM duration, SCP density, and DCP density were entered. The AUC, sensitivity, and specificity for detecting early-stage DR were 0.72 (95% CI: [0.60, 0.84]), 66%, and 76%, respectively. The AUC, sensitivity, and specificity in the validation cohort were 0.74 (95% CI: [0.65, 0.83]), 74%, and 72%, respectively. The statistical power of the development and validation cohorts in two models was all more than 99%. Conclusions. Compared to the logistic regression model, the classification tree model has similar accuracy in predicting early-stage DR. The classification tree model with OCTA variables may be a simple tool for clinical practitioners to identify early-stage DR in T2DM patients. Moreover, SCP density is significantly reduced in mild-to-moderate NPDR eyes and might be a biomarker in early-stage DR detection. Further improvement and validation of the DR diagnostic model are awaiting to be performed.
Does the Stoic Body Have a Head?
Authors: Niles T.R. 
Published: February 2022

Abstract
The interpretation of the Christology of Colossians in modern scholarship has depended to a certain extent upon an analysis of Stoic philosophy as a potential conceptual background for the affirmation in Col 1:18a that Christ is “the head of the body.” If the “body” spoken of here is the body of the cosmos as the Stoics understood it, then Christ must be its “cosmic head.” This article examines whether this works on Stoicism’s own terms; that is, would a Stoic have advanced the notion that the cosmic body has a head?