bluuebunny/crossref_metadata_2025 huggingface dataset:
Futures past and futures present: Geopolitical thought and intellectual history
Authors: Ferraz de Oliveira António
Published: April 2023

Renewed efforts to write geography's intellectual histories hold promise for re-imagining our hereafter. True for the discipline as a whole, this holds particularly true for geopolitics. Beyond restating the infamy of some figures in this tradition, present-day opportunities lie in three growing orientations: (1) pluralizing our canon through the recovery of non-Western and radical progressive thinkers, (2) deepening our study through digital methods and interdisciplinary dialogue; and (3) rewriting the intellectual histories of geopolitics entwined with contemporary concerns such as climate change, racial injustice, democratic failure, and techno-optimism. Through these three orientations, we may give ourselves a powerful means to re-imagine our future more humbly, critically, and creatively. A better appreciation of the past's latent possibilities, cautionary failures, and imperfect successes may yet inspire us to think and act more effectively in struggling towards better worlds. Futures past may then speak to futures present, summoning us to greater boldness and realism.
Simultaneous adjunctive treatment of malaria and its coevolved genetic disorder sickle cell anemia
Authors: Safeukui Innocent , Ware Russell E. , Mohandas Narla , Haldar Kasturi
Published: April 2023

Effective treatments for genetic disorders that coevolved with pathogens require simultaneous betterment of both conditions. Hydroxyurea (HU) offers safe and efficacious treatment for sickle cell anemia (SCA) by reducing clinical complications, transfusions, and death rates. Despite concerns that the HU treatment for SCA would increase infection risk by the human malaria Plasmodium falciparum, (the genetic driver of the sickle mutation), HU instead reduced clinical malaria. We used physiologically relevant drug exposures that mimic in vivo pharmacokinetics in humans. Under these conditions, we showed that HU and other ribonucleotide reductase (RNR) inhibitors have significant, intrinsic killing activity in vitro against schizont stages of P falciparum in both normal and sickle red blood cells. Long-term in vitro selection with HU increased the expression of Pfrnr genes but showed a low risk of eliciting stably resistant parasites or compromising the potency of current antimalarial drugs. Additive activity devoid of antagonism by HU was observed with a wide spectrum of commonly used antimalarial treatments. These data endorse broad, safe, and long-term use of HU for SCA in malaria-endemic countries and provide a novel biological model for the treatment of a genetic disorder with simultaneous, adjunct therapy of a life-threatening infection needed in a global health setting.
Machine learning and drug discovery for neglected tropical diseases
Authors: Breslin William , Pham Doan
Published: April 2023

Neglected tropical diseases affect millions of individuals and cause loss of productivity worldwide. They are common in developing countries without the financial resources for research and drug development. With increased availability of data from high throughput screening, machine learning has been introduced into the drug discovery process. Models can be trained to predict biological activities of compounds before working in the lab. In this study, we use three publicly available, high-throughput screening datasets to train machine learning models to predict biological activities related to inhibition of species that cause leishmaniasis, American trypanosomiasis (Chagas disease), and African trypanosomiasis (sleeping sickness). We compare machine learning models (tree based models, naive Bayes classifiers, and neural networks), featurizing methods (circular fingerprints, MACCS fingerprints, and RDKit descriptors), and techniques to deal with the imbalanced data (oversampling, undersampling, class weight/sample weight).
Silicon, by promoting a homeostatic balance of C:N:P and nutrient use efficiency, attenuates K deficiency, favoring sustainable bean cultivation
Authors: Costa Milton G. , Prado Renato de M. , Santos Sarah Marcilene M. , Souza Júnior Jonas P. , de Souza Antonia Erica S.
Published: April 2023

Background

In many regions of the world, K is being depleted from soils due to agricultural intensification a lack of accessibility, and the high cost of K. Thus, there is an urgent need for a sustainable strategy for crops in this environment. Si is an option for mitigating stress due to nutritional deficiency. However, the underlying effects of Si in mitigating K deficiency C:N:P homeostasis still remains unknown for bean plants. This is a species of great worldwide importance. Thus, this study aims to evaluate whether i) K deficiency modifies the homeostatic balance of C, N and P, and, if so, ii) Si supply can reduce damage caused to nutritional stoichiometry, nutrient use efficiency, and production of dry mass in bean plants.

Results

K deficiency caused a reduction in the stoichiometric ratios C:N, C:P, and P:Si in shoots and C:N, C:P, C:Si, N:Si, and P:Si in roots, resulting in a decrease in K content and use efficiency and reducing biomass production. The application of Si in K-deficient plants modified the ratios C:N, C:Si, N:P, N:Si, and P:Si in shoots and C:N, C:P, C:Si, N:Si, N:P, and P:Si in roots, increasing the K content and efficiency, reducing the loss of biomass. In bean plants with K sufficiency, Si also changed the stoichiometric ratios C:N, C:P, C:Si, N:P, N:Si, and P:Si in shoots and C:N, C:Si, N:Si, and P:Si in roots, increasing K content only in roots and the use efficiency of C and P in shoots and C, N, and P in roots, increasing the biomass production only in roots.

Conclusion

K deficiency causes damage to the C:N:P homeostatic balance, reducing the efficiency of nutrient use and biomass production. However, Si is a viable alternative to attenuate these nutritional damages, favoring bean growth. The future perspective is that the use of Si in agriculture in underdeveloped economies with restrictions on the use of K will constitute a sustainable strategy to increase food security.
Penehyclidine hydrochloride for treating postoperative nausea and vomiting after laparoscopic bariatric surgery: a double-blinded randomized controlled trial
Authors: Ding Xiahao , Chen Dapeng , Che Jinxing , Xu Siyang , Liang Hui , Gui Bo
Published: April 2023

Background

Postoperative nausea and vomiting (PONV) is a common and distressing complication of laparoscopic bariatric surgery (LBS). Penehyclidine hydrochloride has been reported to be effective in preventing PONV. Considering the potential preventive effects of penehyclidine against PONV, we hypothesized that intravenous infusion of penehyclidine may alleviate PONV within the first 48 h in patients scheduled for LBS.

Methods

Patients who underwent LBS were randomly assigned (1:2) to receive saline (Control group, n = 113) or a single intravenous dose of penehyclidine 0.5 mg (PHC group, n = 221). The primary outcome was incidence of PONV within the first 48 h postoperatively. Secondary endpoints included severity of PONV, need for rescue antiemetic therapy, volume of water intake, and time to first flatus.

Results

PONV occurred in 159 (48%) patients within the first 48 h postoperatively, including 51% in the Control group and 46% in the PHC group. There was no significant difference in the incidence or severity of PONV between the two groups (P > 0.05). Within the first 24 h and 24–48 h, no significant difference was found in incidence or severity of PONV, postoperative nausea, postoperative vomiting, need for rescue antiemetic therapy, or volume of water intake (P > 0.05). Kaplan–Meier curves showed that penehyclidine was significantly associated with a prolonged time to first flatus (median onset time: 22 h vs. 21 h, P = 0.036).

Conclusions

Penehyclidine did not decrease incidence and severity of PONV in patients undergoing LBS. However, a single intravenous dose of penehyclidine (0.5 mg) was associated with a slightly prolonged time to first flatus.

Trial registration

Chinese Clinical Trial Registry (ChiCTR2100052418, http://www.chictr.org.cn/showprojen.aspx?proj=134893, date of registration: 25/10/2021).
Screw fixation without fusion for low lumbar chance fracture accompanied by spinal epidural hematoma in patient with ankylosing spondylitis
Authors: Kim Dae Kyun , Kim Seok Won
Published: April 2023

Ankylosing spondylitis (AS) is a chronic inflammatory disease involving the sacroiliac joint and axial spine. AS may render the ankylosed spine prone to trauma and cause an increased frequency of associated epidural hematomas in spine fractures. Herein, we report a rare case of L5 chance fracture and epidural hematoma in a 27-year-old female patient with AS. She was treated surgically but without bone fusion or decompressive laminectomy due to the neurologically intact status despite significant neural compression by the spinal epidural hematoma (SEH). We believe that conservative treatment with close observation of neurological status may be effective in SEH presenting with mild neurological symptoms despite significant neural compression.
Rating of physiotherapy student clinical performance in a paediatric setting: are assessors consistent in their rating of a simulated clinical student performance?
Authors: Fulton Tessa , Myatt Kerry , Kirwan Garry W , Clark Courtney R , Dalton Megan
Published: April 2023

Background

During workplace-based clinical placements, best practice assessment states students should expect consistency between assessors rating their performance. To assist clinical educators (CEs) to provide consistent assessment of physiotherapy student performance, nine paediatric vignettes depicting various standards of simulated student performance, as assessed by the Assessment of Physiotherapy Practice (APP), were developed. The APP defines adequate on the global rating scale (GRS) as the minimally acceptable standard for an entry-level physiotherapist. The project aimed to evaluate consistency of paediatric physiotherapy educators assessing simulated student performance using the APP GRS.

Methods

Three paediatric scenarios representing neurodevelopment across three age ranges, infant, toddler and adolescent, were developed and scripted that depicted a ‘not adequate’, ‘adequate’ and ‘good-excellent’ performance based on the APP GRS. An expert panel (n = 9) conducted face and content validation. Once agreement was reached for all scripts, each video was filmed. A purposive sample of physiotherapists providing paediatric clinical education in Australia were invited to participate in the study. Thirty-five CEs, with minimum 3-years clinical experience and had supervised a student within the past year, were sent three videos at four-week intervals. Videos depicted the same clinical scenario, however performance varied with each video. Participants rated the performance on the four categories: ‘not adequate’, ‘adequate’, ‘good’ and ‘excellent’ Consistency among raters was assessed using percentage agreement to establish reliability.

Results

The vignettes were assessed a combined total of 59 times. Across scenarios, percentage agreement at the not adequate level was 100%. In contrast, the adequate scenarios for the Infant, Toddler and Adolescent video failed to meet the 75% agreement level. However, when combining adequate or good-excellent, percentage agreement was > 86%. The study demonstrated strong consensus when comparing not adequate to adequate or better performance. Importantly, no performance scripted as not adequate was passed by any assessor.

Conclusions

Experienced educators demonstrate consistency in identifying not adequate from adequate or good-excellent performance when assessing a simulated student performance using the APP. Recommendation for practice: These validated video vignettes will be a valuable training tool to improve educator consistency when assessing student performance in paediatric physiotherapy.
HDL and LDL have distinct, opposing effects on LPS-induced brain inflammation
Authors: Radford-Smith Daniel E. , Yates Abi G. , Rizvi Laila , Anthony Daniel C. , Probert Fay
Published: April 2023

Endotoxemia and sepsis induce neuroinflammation and increase the risk of neurodegenerative disorders although the mechanism by which peripheral infection leads to brain inflammation is not well understood. While circulating serum lipoproteins are known immunometabolites with the potential to modulate the acute phase response and cross the blood brain barrier, their contribution to neuroinflammation during systemic infection is unknown. The objective of this study was to elucidate the mechanisms by which lipoprotein subclasses modulate lipopolysaccharide (LPS)-induced neuroinflammation. Adult C57BL/6 mice were divided into 6 treatment groups, including a sterile saline vehicle control group (n = 9), an LPS group (n = 11), a premixed LPS + HDL group (n = 6), a premixed LPS + LDL group (n = 5), a HDL only group (n = 6) and an LDL only group (n = 3). In all cases injections were administered intraperitoneally. LPS was administered at 0.5 mg/kg, and lipoproteins were administered at 20 mg/kg. Behavioural testing and tissue collection was performed 6 h post-injection. The magnitude of peripheral and central inflammation was determined by qPCR of pro-inflammatory genes in fresh liver and brain. Metabolite profiles of liver, plasma and brain were determined by 1H NMR. Endotoxin concentration in the brain was measured by the Limulus Amoebocyte Lysate (LAL) assay. Co-administration of LPS + HDL exacerbated both peripheral and central inflammation, whilst LPS + LDL attenuated this inflammation. Metabolomic analysis identified several metabolites significantly associated with LPS-induced inflammation, which were partially rescued by LDL, but not HDL. Endotoxin was detected at significantly greater concentrations in the brains of animals that received LPS + HDL compared to LPS + saline, but not those that received LPS + LDL. These results suggest that HDL may promote neuroinflammation through direct shuttling of endotoxin to the brain. In contrast, LDL was shown to have anti-neuroinflammatory properties in this study. Our results indicate that lipoproteins may be useful targets in neuroinflammation and neurodegeneration associated with endotoxemia and sepsis.
Blue light exposure collapses the inner blood-retinal barrier by accelerating endothelial CLDN5 degradation through the disturbance of GNAZ and the activation of ADAM17
Authors: Chan Yen-Ju , Hsiao George , Wan Wang-Nok , Yang Tsung-Min , Tsai Chi-Hao , Kang Jaw-Jou , Lee Yu-Cheng , Fang Te-Chao , Cheng Yu-Wen , Li Ching-Hao
Published: April 2023

Blue light is part of the natural light spectrum that emits high energy. Currently, people are frequently exposed to blue light from 3C devices, resulting in a growing incidence of retinopathy. The retinal vasculature is complex, and retinal vessels not only serve the metabolic needs of the retinal sublayers, but also maintain electrolyte homeostasis by forming the inner blood-retinal barrier (iBRB). The iBRB, which is primarily composed of endothelial cells, has well-developed tight junctions. However, with exposure to blue light, the risks of targeting retinal endothelial cells are currently unknown. We found that endothelial claudin-5 (CLDN5) was rapidly degraded under blue light, coinciding with the activation of a disintegrin and metalloprotease 17 (ADAM17), even at non-cytotoxic lighting. An apparently broken tight junction and a permeable paracellular cleft were observed. Mice exposed to blue light displayed iBRB leakage, conferring attenuation of the electroretinogram b-wave and oscillatory potentials. Both pharmacological and genetic inhibition of ADAM17 remarkably alleviated CLDN5 degradation induced by blue light. Under untreated condition, ADAM17 is sequestered by GNAZ (a circadian-responsive, retina-enriched inhibitory G protein), whereas ADAM17 escapes from GNAZ by blue light illuminance. GNAZ knockdown led to ADAM17 hyperactivation, CLDN5 downregulation, and paracellular permeability in vitro, and retinal damage mimicked blue light exposure in vivo. These data demonstrate that blue light exposure might impair the iBRB by accelerating CLDN5 degradation through the disturbance of the GNAZ-ADAM17 axis.
Mid-term follow-up evaluation of a new arthroscopic Broström procedure for chronic lateral ankle instability
Authors: Liu Zhongdi , Lu Hao , Yuan Yusong , Fu Zhongguo , Xu Hailin
Published: April 2023

Background

Chronic lateral ankle instability (CLAI) usually progresses from a previous lateral ankle sprain that was not treated properly. Several procedures have been introduced to address these patients, including open or arthroscopic techniques, the most common of which is the Broström procedure. Here, we describe a new outside-in arthroscopic Broström procedure and its results for treating patients with CLAI.

Methods

Thirty-nine patients (16 male and 23 female; mean age, 35 years [range, 16–60 years]) with CLAI were treated arthroscopically after failing non-operative management. All patients were symptomatic with a combination of recurrent ankle sprains, “giving way,” and avoidance of sports and presented with a positive anterior drawer test upon the physical examination. All patients underwent arthroscopic lateral ligament reconstruction using the new technique. Patient characteristics and pre- and postoperative visual analog scale (VAS), American Orthopedic Foot and Ankle Society Ankle-Hindfoot Scale system (AOFAS), and Karlsson scores were recorded.

Results

The mean AOFAS score increased from 48 (mean 48, range 33–72) preoperatively to 91 (mean 91, range 75–98) at the final follow-up, Karlsson–Peterson and FAAM scores were also significantly improved. Two patients (5.13%) reported superficial peroneal nerve irritation symptoms postoperatively. Three patients (7.69%) complained of mild pain anteroinferior to the lateral ankle.

Conclusions

The arthroscopic outside-in Broström procedure with a single suture anchor was a safe, effective, and reproducible technique for CLAI. Ankle stability resumed with a high clinical success rate. The main complication was injury to the superficial peroneal nerve, which crossed the area of repair.
Preoperative respiratory muscle training combined with aerobic exercise improves respiratory vital capacity and daily life activity following surgical treatment for myasthenia gravis
Authors: Chen Sai , Li Xin , Wu Yunshan , Li Yana , Cao Peili , Yin Yuchun , Chen Zhenguang
Published: April 2023

Objective

The effects of preoperative respiratory muscle training (RMT) on postoperative complications in patients surgically treated for myasthenia gravis (MG) remain unclear. The present study therefore evaluated the effects of preoperative moderate-to-intense RMT and aerobic exercise, when added to respiratory physiotherapy, on respiratory vital capacity, exercise capacity, and duration of hospital stay in patients with MG.

Methods

Eighty patients with MG scheduled for extended thymectomy were randomly divided into two groups. The 40 subjects in the study group (SG) received preoperative moderate-to-intense RMT and aerobic exercise in addition to respiratory physiotherapy, whereas the 40 subjects in the control group (CG) received only chest physiotherapy. Respiratory vital capacity (as determined by VC, FVC, FEV1, FEV1/FVC, and PEF) and exercise capacity (as determined by the 6-min walk test [6 MWT]) were measured pre- and postoperatively and before discharge. The duration of hospital stay and activity of daily living (ADL) were also determined.

Results

Demographic and surgical characteristics, along with preoperative vital capacity and exercise capacity, were similar in the two groups. In the CG, VC (p = 0.001), FVC (p = 0.001), FEV1 (p = 0.002), PEF (p = 0.004), and 6MWT (p = 0.041) were significantly lower postoperatively than preoperatively, whereas the FEV1/FVC ratio did not differ significantly. Postoperative VC (p = 0.012), FVC (p = 0.030), FEV1 (p = 0.014), and PEF (p = 0.035) were significantly higher in the SG than in the CG, although 6MWT results did not differ. ADL on postoperative day 5 was significantly higher in the SG than in the CG (p = 0.001).

Conclusion

RMT and aerobic exercise can have positive effects on postoperative respiratory vital capacity and daily life activity, and would enhance recovery after surgery in MG patients.
Clonorchis sinensis granulin promotes malignant transformation of human intrahepatic biliary epithelial cells through interaction with M2 macrophages via regulation of STAT3 phosphorylation and the MEK/ERK pathway
Authors: He Qing , Pan Xiaowen , Yin Yingxuan , Xu Anyuan , Yi Xueqing , Wu Yinjuan , Li Xuerong
Published: April 2023

Background

Clonorchis sinensis granulin (CsGRN), a component of the excretory/secretory products of this species, is a multifunctional growth factor that can promote the metastasis of cholangiocarcinoma cells. However, the effect of CsGRN on human intrahepatic biliary epithelial cells (HIBECs) is unclear. Here, we investigated the effect of CsGRN on the malignant transformation of HIBECs and its possible underlying mechanism.

Methods

The malignant transformation phenotypes of HIBECs after CsGRN treatment were estimated by EdU-488 incorporation assay, colony formation assay, wound-healing assay, Transwell assay and western blot. The biliary damage of CsGRN-treated mice was detected by western blot, immunohistochemical staining and hematoxylin and eosin staining. The phenotypes of the macrophages [human monocytic leukemia cell line (THP-1)] were analyzed by flow cytometry, immunofluorescence and immunohistochemistry, both in vitro and in vivo. A co-culture system was developed to explore the interaction between THP-1 and HIBECs in CsGRN-containing medium. Enzyme-linked immunosorbent assay and western blot were used to detected the activation of interleukin 6 (IL-6), phosphorylated signal transducer and activator of transcription 3 (p-STAT3) and the mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway. An inhibitor of the MEK/ERK pathway, PD98059, was used to determine whether this pathway is involved in CsGRN-mediated cell interactions as well as in STAT3 phosphorylation and malignant transformation of HIBECs.

Results

Excessive hyperplasia and abnormal proliferation of HIBECs, enhanced secretion of hepatic pro-inflammatory cytokines and chemokines, as well as biliary damage, were observed in vitro and in vivo after treatment with CsGRN. The expression of the markers of M2 macrophages significantly increased in CsGRN-treated THP-1 cells and biliary duct tissues compared with the controls. Moreover, following treatment with CsGRN, the HIBECs underwent malignant transformation in the THP-1-HIBECs co-culture group. In addition, high expression of IL-6 was observed in the CsGRN-treated co-culture media, which activated the phosphorylation of STAT3, JAK2, MEK and ERK. However, treatment with an inhibitor of the MEK/ERK pathway, PD98059, decreased expression of p-STAT3 in CsGRN-treated HIBECs and further repressed the malignant transformation of HIBECs.

Conclusions

Our results demonstrated that, by inducing the M2-type polarization of macrophages and activating the IL-6/JAK2/STAT3 and MEK/ERK pathways in HIBECs, CsGRN promoted the malignant transformation of the latter.

Graphical abstract
Post-activation effects of accommodating resistance and different rest intervals on vertical jump performance in strength trained males
Authors: Masel Sebastian , Maciejczyk Marcin
Published: April 2023

Background

Post-activation potentiation performance (PAPE) is a physiological phenomenon that has been studied numerously but the researchers are still seeking for the optimal application methods. The accommodating resistance was found to be an effective training method to acutely enhance subsequent explosive performance. The purpose of this study was to evaluate the effects of performing a trap bar deadlift with accommodating resistance on squat jump (SJ) performance with different rest intervals (90, 120, 150s).

Methods

The study had a cross-over design and fifteen strength-trained males (age 22.9 ± 2.1 years; body height 182 ± 6.5 cm; body mass: 80.4 ± 9.8 kg; body fat 15.8 ± 7.0%; BMI 24.1 ± 2.8; lean body mass 67.5 ± 8.8 kg) participated in one familiarization, three experimental and three control sessions within three weeks. The conditioning activity (CA) used in the study was a single set of 3 repetitions of a trap bar deadlift at 80% 1RM with approximately 15% 1RM of an elastic band. The SJ measurements were performed at the baseline and post-CA after 90 or 120 or 150s.

Results

The 90s experimental protocol significantly improved (p < 0.05, effect size 0.34) acute SJ performance whereas 120 and 150 s experimental protocols did not significantly improve performance. The following tendency was observed - the longer the rest interval, the smaller the potentiation effect; p value for 90s (0.046), 120s (0.166), 150s (0.745).

Conclusions

A trap bar deadlift with accommodating resistance and 90s rest interval can be used to acutely enhance jump performance. A 90s rest interval was found to be optimal to enhance subsequent SJ performance, but the potential rest interval extension to 120s could also be taken by strength and conditioning coaches as the PAPE effect is highly individual. However, exceeding the rest interval to more than 120s may not be effective in optimising the PAPE effect.
Machine learning combined with radiomics and deep learning features extracted from CT images: a novel AI model to distinguish benign from malignant ovarian tumors
Authors: Jan Ya-Ting , Tsai Pei-Shan , Huang Wen-Hui , Chou Ling-Ying , Huang Shih-Chieh , Wang Jing-Zhe , Lu Pei-Hsuan , Lin Dao-Chen , Yen Chun-Sheng , Teng Ju-Ping , Mok Greta S. P. , Shih Cheng-Ting , Wu Tung-Hsin
Published: April 2023

Background

To develop an artificial intelligence (AI) model with radiomics and deep learning (DL) features extracted from CT images to distinguish benign from malignant ovarian tumors.

Methods

We enrolled 149 patients with pathologically confirmed ovarian tumors. A total of 185 tumors were included and divided into training and testing sets in a 7:3 ratio. All tumors were manually segmented from preoperative contrast-enhanced CT images. CT image features were extracted using radiomics and DL. Five models with different combinations of feature sets were built. Benign and malignant tumors were classified using machine learning (ML) classifiers. The model performance was compared with five radiologists on the testing set.

Results

 Among the five models, the best performing model is the ensemble model with a combination of radiomics, DL, and clinical feature sets. The model achieved an accuracy of 82%, specificity of 89% and sensitivity of 68%. Compared with junior radiologists averaged results, the model had a higher accuracy (82% vs 66%) and specificity (89% vs 65%) with comparable sensitivity (68% vs 67%). With the assistance of the model, the junior radiologists achieved a higher average accuracy (81% vs 66%), specificity (80% vs 65%), and sensitivity (82% vs 67%), approaching to the performance of senior radiologists.

Conclusions

 We developed a CT-based AI model that can differentiate benign and malignant ovarian tumors with high accuracy and specificity. This model significantly improved the performance of less-experienced radiologists in ovarian tumor assessment, and may potentially guide gynecologists to provide better therapeutic strategies for these patients.
TNF-α/IL-1β-licensed hADSCs alleviate cholestatic liver injury and fibrosis in mice via COX-2/PGE2 pathway
Authors: Luan Xiaoyu , Chen Peng , Li Yaxin , Yuan Xinying , Miao Longyu , Zhang Pengyu , Cao Qilong , Song Xiaomin , Di Guohu
Published: April 2023

Background

Adipose tissue-derived stem cell (ADSC) transplantation has been shown to be effective for the management of severe liver disorders. Preactivation of ADSCs enhanced their therapeutic efficacy. However, these effects have not yet been examined in relation to cholestatic liver injury.

Methods

In the present study, a cholestatic liver injury model was established by bile duct ligation (BDL) in male C57BL/6 mice. Human ADSCs (hADSCs) with or without tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) pretreatment were administrated into the mice via tail vein injections. The efficacy of hADSCs on BDL-induced liver injury was assessed by histological staining, real-time quantitative PCR (RT-qPCR), Western blot, and enzyme-linked immune sorbent assay (ELISA). In vitro, the effects of hADSC conditioned medium on the activation of hepatic stellate cells (HSCs) were investigated. Small interfering RNA (siRNA) was used to knock down cyclooxygenase-2 (COX-2) in hADSCs.

Results

TNF-α/IL-1β preconditioning could downregulate immunogenic gene expression and enhance the engraftment efficiency of hADSCs. Compared to control hADSCs (C-hADSCs), TNF-α/IL-1β-pretreated hADSCs (P-hADSCs) significantly alleviated BDL-induced liver injury, as demonstrated by reduced hepatic cell death, attenuated infiltration of Ly6G + neutrophils, and decreased expression of pro-inflammatory cytokines TNF-α, IL-1β, C-X-C motif chemokine ligand 1 (CXCL1), and C-X-C motif chemokine ligand 2 (CXCL2). Moreover, P-hADSCs significantly delayed the development of BDL-induced liver fibrosis. In vitro, conditioned medium from P-hADSCs significantly inhibited HSC activation compared to that from C-hADSCs. Mechanistically, TNF-α/IL-1β upregulated COX-2 expression and increased prostaglandin E2 (PGE2) secretion. The blockage of COX-2 by siRNA transfection reversed the benefits of P-hADSCs for PGE2 production, HSC activation, and liver fibrosis progression.

Conclusion

In conclusion, our results suggest that TNF-α/IL-1β pretreatment enhances the efficacy of hADSCs in mice with cholestatic liver injury, partially through the COX-2/PGE2 pathway.
CMR validation of left ventricular volumes and ejection fraction measured by the IQ-SPECT system in patients with small heart size
Authors: Wei Hua , Wu Jiaojiao , Han Ke , Hu Guang , Wang Hongliang , Guo Xiaoshan , Liu Haiyan , Wu Zhifang , Li Sijin
Published: April 2023

Background

The IQ-SPECT system is equipped with multifocal collimators and uses ordered-subset conjugate gradient minimization (OSCGM) as its reconstruction algorithm, achieving a shorter acquisition time than conventional SPECT. Left ventricular ejection fraction (LVEF) is overestimated by conventional SPECT in patients with small heart size. In this study, we compared IQ-SPECT with conventional SPECT and cardiovascular magnetic resonance (CMR) for the estimation of LVEF in patients with small hearts (males: EDV ≤ 60 ml, ESV ≤ 25 ml; females: EDV ≤ 45 ml, ESV ≤ 20 ml).

Methods

The study consisted of 49 consecutive patients (20 normal and 29 with small heart size) undergoing gated myocardial perfusion imaging (GMPI) with a 99mTc-labelled agent during stress or rest to assess the risk of coronary artery disease (CAD). The data were reconstructed using filtered back-projection (FBP) for conventional SPECT and OSCGM for IQ-SPECT. ESV, EDV, and LVEF were calculated using quantitative gated SPECT (QGS). To determine the optimal ordered-subset reconstruction parameters, we compared the LVEF from SPECT to the corresponding measurement from CMR.

Results

EDV, ESV, and LVEF values obtained from IQ-SPECT and conventional SPECT showed that the results of these two forms of SPECT were significantly correlated, although the EDV and ESV obtained by IQ-SPECT were higher than those obtained by conventional SPECT. IQ-SPECT yielded lower LVEF measurements than conventional SPECT (normal heart size: 50.6 ± 4.3% vs. 73.4 ± 8.4%, P = 0.002; small heart size: 62.1 ± 7.8% vs. 75.0 ± 11.4%, P < 0.001). There were no significant differences in LVEF measurements made by IQ-SPECT and CMR (normal heart size: 50.6 ± 4.3% vs. 53.2 ± 5.8%, P > 0.05; small heart size: 62.1 ± 7.8% vs. 64.6 ± 8.8%, P > 0.05). Five subsets (S) and 12 iterations (I) did not differ significantly in LVEF between CMR and IQ-SPECT for patients with small hearts (64.6 ± 8.8% vs. 62.1 ± 7.8%, P = 0.120), while 3 S and 10 I were the best parameters for patients with normal heart size (50.6 ± 4.3% vs. 53.1 ± 5.8%, P = 0.117).

Conclusion

With CMR as the standard, IQ-SPECT yields more reliable LVEF values than conventional SPECT for populations with small heart size. The best reconstruction parameters from IQ-SPECT were 5 S and 12 I for patients with small hearts.
Quantitative evidence synthesis: a practical guide on meta-analysis, meta-regression, and publication bias tests for environmental sciences
Authors: Nakagawa Shinichi , Yang Yefeng , Macartney Erin L. , Spake Rebecca , Lagisz Malgorzata
Published: April 2023

Meta-analysis is a quantitative way of synthesizing results from multiple studies to obtain reliable evidence of an intervention or phenomenon. Indeed, an increasing number of meta-analyses are conducted in environmental sciences, and resulting meta-analytic evidence is often used in environmental policies and decision-making. We conducted a survey of recent meta-analyses in environmental sciences and found poor standards of current meta-analytic practice and reporting. For example, only ~ 40% of the 73 reviewed meta-analyses reported heterogeneity (variation among effect sizes beyond sampling error), and publication bias was assessed in fewer than half. Furthermore, although almost all the meta-analyses had multiple effect sizes originating from the same studies, non-independence among effect sizes was considered in only half of the meta-analyses. To improve the implementation of meta-analysis in environmental sciences, we here outline practical guidance for conducting a meta-analysis in environmental sciences. We describe the key concepts of effect size and meta-analysis and detail procedures for fitting multilevel meta-analysis and meta-regression models and performing associated publication bias tests. We demonstrate a clear need for environmental scientists to embrace multilevel meta-analytic models, which explicitly model dependence among effect sizes, rather than the commonly used random-effects models. Further, we discuss how reporting and visual presentations of meta-analytic results can be much improved by following reporting guidelines such as PRISMA-EcoEvo (Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Ecology and Evolutionary Biology). This paper, along with the accompanying online tutorial, serves as a practical guide on conducting a complete set of meta-analytic procedures (i.e., meta-analysis, heterogeneity quantification, meta-regression, publication bias tests and sensitivity analysis) and also as a gateway to more advanced, yet appropriate, methods.
Canadian multidisciplinary expert consensus on the use of biologics in upper airways: A Delphi study
Authors: Thamboo Andrew V. , Lee Melissa , Bhutani Mohit , Chan Charles , Chan Yvonne , Chapman Ken R. , Chin Christopher J. , Connors Lori , Dorscheid Del , Ellis Anne K. , Gall Richard M. , Godbout Krystelle , Janjua Arif , Javer Amin , Kilty Shaun , Kim Harold , Kirkpatrick Gordon , Lee John M. , Leigh Richard , Lemiere Catherine , Monteiro Eric , Neighbour Helen , Keith Paul K. , Philteos George , Quirt Jaclyn , Rotenberg Brian , Ruiz Juan C. , Scott John R. , Sommer Doron D. , Sowerby Leigh , Tewfik Marc , Waserman Susan , Witterick Ian , Wright Erin D. , Yamashita Cory , Desrosiers Martin
Published: April 2023

Background

Chronic rhinosinusitis with nasal polyposis (CRSwNP) often coexists with lower airway disease. With the overlap between upper and lower airway disease, optimal management of the upper airways is undertaken in conjunction with that of the lower airways. Biologic therapy with targeted activity within the Type 2 inflammatory pathway can improve the clinical signs and symptoms of both upper and lower airway diseases. Knowledge gaps nevertheless exist in how best to approach patient care as a whole. There have been sixteen randomized, double-blind, placebo-controlled trails performed for CRSwNP targeted components of the Type 2 inflammatory pathway, notably interleukin (IL)-4, IL-5 and IL-13, IL- 5R, IL-33, and immunoglobulin (Ig)E. This white paper considers the perspectives of experts in various disciplines such as rhinology, allergy, and respirology across Canada, all of whom have unique and valuable insights to contribute on how to best approach patients with upper airway disease from a multidisciplinary perspective.

Methods

A Delphi Method process was utilized involving three rounds of questionnaires in which the first two were completed individually online and the third was discussed on a virtual platform with all the panelists. A national multidisciplinary expert panel of 34 certified specialists was created, composed of 16 rhinologists, 7 allergists, and 11 respirologists who evaluated the 20 original statements on a scale of 1–9 and provided comments. All ratings were quantitively reviewed by mean, median, mode, range, standard deviation and inter-rater reliability. Consensus was defined by relative interrater reliability measures—kappa coefficient ([Formula: see text] [Formula: see text]) value > 0.61.

Results

After three rounds, a total of 22 statements achieved consensus. This white paper only contains the final agreed upon statements and clear rationale and support for the statements regarding the use of biologics in patients with upper airway disease.

Conclusion

This white paper provides guidance to Canadian physicians on the use of biologic therapy for the management of upper airway disease from a multidisciplinary perspective, but the medical and surgical regimen should ultimately be individualized to the patient. As more biologics become available and additional trials are published we will provide updated versions of this white paper every few years.

Graphical Abstract
Absence of Cretaceous hairpin in the apparent polar wander path of southwest Japan: consistency in paleomagnetic pole positions
Authors: Uno Koji , Ohara Honoka , Furukawa Kuniyuki , Kanamaru Tatsuo
Published: April 2023

To test the hypothesis that a Cretaceous hairpin turn is absent in the apparent polar wander path (APWP) of the inner arc of southwestern Japanese island (southwest Japan), we refined a mid-Cretaceous (100 Ma) paleomagnetic pole from southwest Japan. Red mudstone samples from the 100 Ma Hayama Formation were collected for paleomagnetic analysis from eight sites in the Hayama area in the central part of southwest Japan. A high-temperature remanent magnetization component carried by hematite was isolated from these sites and was found to be of primary mid-Cretaceous origin. The primary nature of the magnetization is supported by the detrital character of the magnetic carrier. The primary directions provided a paleomagnetic pole (35.0°N, 209.6°E, A95 = 6.1°, N = 8), which represented southwest Japan at 100 Ma. This pole falls into a cluster of Cretaceous poles in southwest Japan. An APWP for southwest Japan between 110 and 70 Ma was updated to ascertain the stationarity of the pole positions for this region. Therefore, it is unlikely that the APWP for southwest Japan experienced a hairpin turn during the Cretaceous.
Undergraduate student perceptions of stress and mental health in engineering culture
Authors: Jensen Karin J. , Mirabelli Joseph F. , Kunze Andrea J. , Romanchek Thomas E. , Cross Kelly J.
Published: April 2023

Background

Mental health for engineering undergraduates is an urgent topic for engineering educators. Narratives of engineering education requiring suffering may create or exacerbate problematic perceptions around stress and mental health in engineering. This study explored the roles of stress and mental health in engineering culture. We sought to explore: (1) how engineering students describe their experiences related to stress and mental health and (2) norms and expectations engineering students share about stress and mental health. Qualitative interview data were collected from 30 students who had previously responded to a college-wide survey.

Results

Codes related to experiences with stress and mental health in engineering were organized in a bioecological systems model and analyzed for emergent themes depicting engineering culture. The study identified three themes related to stress and mental health in engineering culture: (1) engineering workload as a defining stressor, (2) specific barriers that prevent engineering students from seeking help for mental health concerns, and (3) reliance on peers to cope with stress and mental health distress.

Conclusions

Our analysis provided insight into how engineering students perceive norms around stress and mental health in engineering and how this impacts help-seeking for mental health challenges. These findings have important implications for developing interventions and positive cultures that support student mental health.
Improved heating method for shape-memory alloy using carbon nanotube and silver paste
Authors: Kim Sang Jin , Kim Sang Un , Vu Chi Cuong , Kim Joo Yong
Published: April 2023

Shape memory alloys (SMAs) have a special ability to remember their initial shape and return from operating temperature. For this special ability, there are many studies in the field of smart wearables to replace rigid, heavy, and large electric actuators with SMAs that can be a fabrication. The usual operating method of the SMA is heating the SMA by direct Joule heating with electricity. Although direct Joule heating is fast and easy, there is overshooting, unstable, and high-power consumption. For these issues to use the SMA as textile actuators, this research suggested a heating method with silver paste required lower power consumption and coating the basic fabric with carbon nanotubes (CNTs) to support heating stability and heat uniformity. The heating method evaluated the efficiency of heat by comparing direct heating and silver layer heating and the uniformity of heat with the infrared images of whether CNTs coated or not. In this research, we reached higher temperatures with lower power than direct Joule heating using wearable heaters manufactured using silver paste. In addition, we confirmed that coating the basic fabric with carbon nanotubes reduce the temperature imbalance, and improved the heating stability. This research is expected that SMA will be used as a wearable actuator to help develop wearable devices that can move.
Regional and socioeconomic inequalities in access to pre-primary education in India: evidence from a recent household survey
Authors: Choudhury Pradeep Kumar , Joshi Radhika , Kumar Amit
Published: April 2023

In India, the National Education Policy 2020 recommends ensuring universal access to high-quality early childhood care and education for children aged 3–6 years by 2030. Using the 75th round of National Statistical Office data (2017–2018), this paper analyses the regional and socioeconomic inequalities in access to pre-primary education. Also, we investigate the specific role of households’ economic status and educational attainment in explaining these inequalities. We find considerable regional (rural/urban) and socioeconomic inequalities in access to pre-primary education in India, with girls and children belonging to historically disadvantaged social groups (scheduled castes and scheduled tribes) less likely to attend early childhood education, particularly in rural areas. We find that a substantial portion of the rural–urban gap in access to pre-primary education can be removed by controls for households’ economic condition and household head’s educational status. In addition, we find gender and socioeconomic inequalities in the household investment in early years education. These findings highlight the need to put policy efforts and commitments to reducing barriers to accessing pre-primary education for children in disadvantaged conditions in India.
Site-specific 68Ga-labeled nanobody for PET imaging of CD70 expression in preclinical tumor models
Authors: Dewulf Jonatan , Flieswasser Tal , Delahaye Tim , Vangestel Christel , Miranda Alan , de Haard Hans , Jacobs Julie , Smits Evelien , Van den Wyngaert Tim , Elvas Filipe
Published: April 2023

Background

CD70-CD27 is a costimulatory ligand-receptor pair in the tumor necrosis factor receptor family. With only limited expression in normal tissues, CD70 is constitutively expressed in a variety of solid tumors and hematologic malignancies, facilitating immunosuppression through CD27 signaling in the tumor microenvironment by enhanced survival of regulatory T cells, induction of T cell apoptosis, and T cell exhaustion. Consequently, CD70 is an increasingly recognized target for developing antibody-based therapies, but its expression patterns vary among different tumor types in spatial distribution, magnitude of expression and percentage of positive cells. In that regard, individual confirmation of CD70 expression at screening and during treatment could enhance the successful implementation of anti-CD70 therapies. Here, we developed a gallium-68 (68Ga) radiolabeled single-domain antibody-fragment targeting CD70 for in vivo positron emission tomography (PET) imaging.

Results

An anti-CD70 VHH construct containing a C-direct-tag with a free thiol was developed to enable site-specific conjugation to a NOTA bifunctional chelator for 68Ga radiolabeling. [68Ga]Ga-NOTA-anti-CD70 VHH was obtained in good radiochemical yield of 30.4 ± 1.7% and high radiochemical purity (> 94%). The radiolabeled VHH showed excellent in vitro and in vivo stability. Specific binding of [68Ga]Ga-NOTA-anti-CD70 VHH was observed on CD70high 786-O cells, showing significantly higher cell-associated activity when compared to the blocking condition (p < 0.0001) and CD70low NCl-H1975 cells (p < 0.0001). PET imaging showed specific radiotracer accumulation in CD70 expressing human tumor xenografts, which was efficiently blocked by prior injection of unlabeled anti-CD70 VHH (p = 0.0029). In addition, radiotracer uptake in CD70high tumors was significantly higher when compared with CD70low tumors (p < 0.0001). The distribution of the radioactivity in the tumors using autoradiography was spatially matched with immunohistochemistry analysis of CD70 expression.

Conclusion

[68Ga]Ga-NOTA-anti-CD70 VHH showed excellent in vivo targeting of CD70 in human cancer xenografts. PET imaging using this radioimmunoconjugate holds promise as a non-invasive method to identify and longitudinally follow-up patients who will benefit most from anti-CD70 therapies.