bluuebunny/crossref_metadata_2025 huggingface dataset:
Heart-targeted amelioration of sepsis-induced myocardial dysfunction by microenvironment responsive nitric oxide nanogenerators in situ
Authors: Ouyang Minzhi , Ouyang Xiangnan , Peng Zefang , Liu Minghui , Xu Ganqiong , Zou Zhen , Zhang Ming , Shang Quanliang
Published: June 2022

Background

A balanced endogenous level of bioavailable nitric oxide (NO) plays a key role in maintaining cardiovascular homeostasis. The bioactive NO level in the cardiomyocytes was much reduced during sepsis. However, it is clinically challenging for the NO gas therapy due to the lack of spatial and temporal release system with precise control. The purpose of this study is to design a NO-releasing biomaterial with heart-targeted capability responsive to the infectious microenvironment, thus ameliorating lipopolysaccharide (LPS)-induced cardiac dysfunction.

Results

The heart-targeted NO delivery and in situ releasing system, PCM-MSN@LA, was synthesized using hollow mesoporous silica nanoparticles (MSN) as the carrier, and L-arginine (LA) as the NO donor. The myocardial delivery was successfully directed to heart by specific peptide (PCM) combined with low-intensity focused ultrasound (LIFU) guidance. The myocardial system synthesized NO from the LA released from PCM-MSN@LA in the presence of increased endogenous nitric oxide synthase (NOS) activity induced by LPS. This targeted NO release in situ achieved extraordinary protective effects against LPS-challenged myocardial injury by reducing the recruitment of inflammatory cells, inhibiting oxidative stress and maintaining the mitochondria integrity. In particular, this protection was not compromised by simultaneous circulation collapse as an adverse event in the context.

Conclusions

PCM-MSN@LA + LIFU exhibited extraordinary cardioprotective effects against severe sepsis in the hearts of LPS-treated animals without the side effect of NO diffusion. This technology has great potential to be served as a novel therapeutic strategy for sepsis-induced myocardial injury.
Polymerized porin as a novel delivery platform for coronavirus vaccine
Authors: Yang Zhongqian , Hua Liangqun , Yang Mengli , Li Weiran , Ren Zhaoling , Zheng Xiao , Chen Haoqian , Long Qiong , Bai Hongmei , Huang Weiwei , Ma Yanbing
Published: June 2022

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), seriously threatens human life and health. The correct folding and polymerization of the receptor-binding domain (RBD) protein of coronavirus in Escherichia coli may reduce the cost of SARS-CoV-2 vaccines. In this study, we constructed this nanopore by using the principle of ClyA porin polymerization triggered by the cell membrane. We used surfactants to "pick" the ClyA-RBD nanopore from the bacterial outer membrane. More importantly, the polymerized RBD displayed on the ClyA-RBD polymerized porin (RBD-PP) already displays some correct spatial conformational epitopes that can induce neutralizing antibodies. The nanostructures of RBD-PP can target lymph nodes and promote antigen uptake and processing by dendritic cells, thereby effectively eliciting the production of anti-SARS-CoV-2 neutralizing antibodies, systemic cellular immune responses, and memory T cells. We applied this PP-based vaccine platform to fabricate an RBD-based subunit vaccine against SARS-CoV-2, which will provide a foundation for the development of inexpensive coronavirus vaccines. The development of a novel vaccine delivery system is an important part of innovative drug research. This novel PP-based vaccine platform is likely to have additional applications, including other viral vaccines, bacterial vaccines, tumor vaccines, drug delivery, and disease diagnosis.

Graphical Abstract
Nasal administration of diacetylmorphine improved the adherence in a patient receiving heroin-assisted treatment
Authors: Meyer Maximilian , Westenberg Jean N. , Strasser Johannes , Dürsteler Kenneth M. , Lang Undine E. , Krausz Michael , Vogel Marc
Published: June 2022

Background

Traditional heroin-assisted treatment in Switzerland consists of oral and injectable diacetylmorphine (pharmaceutical heroin) administration. To date, no suitable treatment option is available for patients who crave rapid onset (“rush”) but are either unable to inject or primarily sniff or inhale illicit heroin. We present a patient who successfully switched to intranasal heroin-assisted treatment following several unsuccessful treatment attempts.

Case presentation

A 29-year-old male with severe opioid use disorder, injection substance use, and concomitant cocaine use, previously prescribed slow-release oral morphine, was started on intravenous diacetylmorphine. Due to complications and harms associated with intravenous injections, nasal diacetylmorphine was prescribed. With this novel route of administration, the patient who had previously been unable to adhere to other OAT options remained in treatment. Health outcomes improved by reduction of injection-related harms, increased adherence to the heroin-assisted treatment regimen, and increased collaboration with the therapeutic staff.

Conclusions

Nasal heroin-assisted treatment can be a feasible therapeutic option for individuals with severe opioid use disorder who crave the fast onset of effect of diacetylmorphine but are unable to inject intravenously.
A mixed methods study of siblings’ roles in maternal feeding practices in early childhood: an application of the learning from experience process
Authors: Ruggiero Cara F. , Moore Amy M. , Marini Michele E. , Kodish Stephen R. , McHale Susan M. , Savage Jennifer S.
Published: June 2022

Background

Firstborn children have higher rates of obesity compared to secondborns, perhaps due, in part, to differential feeding practices. Despite the centrality of siblings in family life and potential for influence, almost nothing is known about the role of siblings in parent feeding practices in early childhood.

Methods

Participants (n = 117) were mothers of consecutively born siblings. Firstborns participated in an RCT that compared a responsive parenting intervention designed for primary prevention of obesity against a safety control. Secondborns participated in an observational cohort. Multilevel models tested whether and how firstborn characteristics (temperament, appetite, rapid weight gain) at 16 weeks and 1 year were associated maternal feeding practices of secondborns in infancy at 16 weeks, 28 weeks, and 1 year (food to soothe) and at ages 1, 2, and 3 years (structure-and control-based feeding practices). A purposive subsample (n = 30) of mothers also participated in semi-structured interviews to further illuminate potential sibling influences on maternal feeding practices during infancy and toddlerhood.

Results

Firstborn characteristics did not predict secondborn feeding in infancy (all ps > 0.05). Firstborn negative affect, however, predicted mothers’ less consistent mealtime routines (b (SE) = − 0.27 (0.09); p = 0.005) and more pressure (b (SE) = 0.38 (0.12); p = 0.001). Firstborn appetite predicted mothers’ less frequent use of food to soothe (b (SE) = − 0.16 (0.07); p = 0.02) when secondborns were toddlers. Firstborn surgency, regulation, and rapid weight gain, however, did not predict secondborn feeding practices during toddlerhood (all ps > 0.05). Interviews with mothers revealed three ways that maternal experiences with firstborns informed feeding practices of secondborns: 1) Use of feeding practices with secondborn that worked for the firstborn; 2) Confidence came from firstborn feeding experiences making secondborn feeding less anxiety-provoking; and 3) Additional experiences with firstborn and other factors that contributed to secondborn feeding practices.

Conclusions

Some firstborn characteristics and maternal experiences with firstborns as well as maternal psychosocial factors may have implications for mothers’ feeding practices with secondborns. Together, these mixed methods findings may inform future research and family-based interventions focused on maternal feeding of siblings in early childhood.
miR-18a-5p derived from mesenchymal stem cells-extracellular vesicles inhibits ovarian cancer cell proliferation, migration, invasion, and chemotherapy resistance
Authors: Wang Xiaoying , Jiang Lili , Liu Qifang
Published: June 2022

Objective

Ovarian cancer (OC) is a major threat to women’s health. Mesenchymal stem cells (MSCs) are key regulators in cellular communication by secreting extracellular vesicles (EVs) that are involved in OC. This study probed into the mechanism of human MSCs derived-EVs (hMSC-EVs) in regulating OC cell growth and chemotherapy resistance.

Methods

hMSCs and EVs were isolated and identified. After adding EVs, the uptake of EVs by OC CAOV3/ES2 cells (for in vitro studies), and cell proliferation, migration, and invasion were detected. Downregulated miRNAs in hMSC-EVs were screened and miR-18a-5p expression in OC patients was detected. The prognosis of OC patients was analyzed. Binding sites of miR-18a-5p and NACC1 were predicted and validated. NACC1 expression in OC tissues was measured by RT-qPCR, and its correlation with miR-18a-5p was analyzed by Pearson method. AKT/mTOR pathway activation was assessed by WB. The cisplatin sensitivity of EVs-treated CAOV3 cells was evaluated via MTT assay and tested by tumor formation assay in nude mice.

Results

hMSC-EVs suppressed OC cell proliferation, migration, and invasion. miR-18a-5p was downregulated in OC and miR-18a-5p low expression was associated with a poor prognosis. EV-encapsulated miR-18a-5p targeted NACC1. NACC1 was upregulated in OC tissues. miR-18a-5p knockdown and NACC1 overexpression both annulled the inhibition of hMSC-EVs on OC cell growth. AKT and mTOR were elevated in OC and NACC1 activated the AKT/mTOR pathway in OC cells. hMSC-EVs promoted cisplatin sensitivity of OC cells by carrying miR-18a-5p.

Conclusion

hMSC-EVs-derived miR-18a-5p inhibits OC cell proliferation, migration, invasion, and chemotherapy resistance.
Perspectives in Immunotherapy: meeting report from the Immunotherapy Bridge, December 1st–2nd, 2021
Authors: Ascierto Paolo A. , Avallone Antonio , Bhardwaj Nina , Bifulco Carlo , Bracarda Sergio , Brody Joshua D. , Buonaguro Luigi , Demaria Sandra , Emens Leisha A. , Ferris Robert L. , Galon Jérôme , Khleif Samir N. , Klebanoff Christopher A. , Laskowski Tamara , Melero Ignacio , Paulos Chrystal M. , Pignata Sandro , Ruella Marco , Svane Inge Marie , Taube Janis M. , Fox Bernard A. , Hwu Patrick , Puzanov Igor
Published: June 2022

Over the past decade, immunotherapy has become an increasingly fundamental modality in the treatment of cancer. The positive impact of immune checkpoint inhibition, especially anti-programmed death (PD)-1/PD-ligand (L)1 blockade, in patients with different cancers has focused attention on the potential for other immunotherapeutic approaches. These include inhibitors of additional immune checkpoints, adoptive cell transfer (ACT), and therapeutic vaccines. Patients with advanced cancers who previously had limited treatment options available may now benefit from immunotherapies that can offer durable responses and improved survival outcomes. However, despite this, a significant proportion of patients fail to respond to immunotherapy, especially those with less immunoresponsive cancer types, and there remains a need for new treatment strategies.

The virtual Immunotherapy Bridge (December 1st–2nd, 2021), organized by the Fondazione Melanoma Onlus, Naples, Italy in collaboration with the Society for Immunotherapy of Cancer addressed several areas of current research in immunotherapy, including lessons learned from cell therapies, drivers of immune response, and trends in immunotherapy across different cancers, and these are summarised here.
Practicalities of implementing burden of disease research in Africa: lessons from a population survey component of our multi-partner FOCAL research project
Authors: Desta Binyam N. , Gobena Tesfaye , Macuamule Custodia , Fayemi Olanrewaju E. , Ayolabi Christianah I. , Mmbaga Blandina T. , Thomas Kate M. , Dodd Warren , Pires Sara M. , Majowicz Shannon E. , Hald Tine
Published: June 2022

Background

Collaborative research is being increasingly implemented in Africa to study health-related issues, for example, the lack of evidence on disease burden, in particular for the presumptive high load of foodborne diseases. The FOCAL (Foodborne disease epidemiology, surveillance, and control in African LMIC) Project is a multi-partner study that includes a population survey to estimate the foodborne disease burden in four African low- and middle-income countries (LMICs). Our multi-partner study team had members from seven countries, all of whom contributed to the project from the grant application stage, and who play(ed) specific roles in designing and implementing the population survey.

Main text

In this paper, we applied Larkan et al.’s framework for successful research partnerships in global health to self-evaluate our project’s collaboration, management, and implementation process. Our partnership formation considered the interplay and balance between operations and relations. Using Larkan et al.’s seven core concepts (i.e., focus, values, equity, benefit, communication, leadership, and resolution), we reviewed the process stated above in an African context.

Conclusion

Through our current partnership and research implementing a population survey to study disease burden in four African LMICs, we observed that successful partnerships need to consider these core concepts explicitly, apply the essential leadership attributes, perform assessment of external contexts before designing the research, and expect differences in work culture. While some of these experiences are common to research projects in general, the other best practices and challenges we discussed can help inform future foodborne disease burden work in Africa.
Potential role of astrocyte angiotensin converting enzyme 2 in the neural transmission of COVID-19 and a neuroinflammatory state induced by smoking and vaping
Authors: Zhang Yong , Archie Sabrina Rahman , Ghanwatkar Yashwardhan , Sharma Sejal , Nozohouri Saeideh , Burks Elizabeth , Mdzinarishvili Alexander , Liu Zijuan , Abbruscato Thomas J.
Published: June 2022

Background

Knowledge of the entry receptors responsible for SARS-CoV-2 is key to understand the neural transmission and pathogenesis of COVID-19 characterized by a neuroinflammatory scenario. Understanding the brain distribution of angiotensin converting enzyme 2 (ACE2), the primary entry receptor for SARS-CoV-2, remains mixed. Smoking has been shown as a risk factor for COVID-19 severity and it is not clear how smoking exacerbates the neural pathogenesis in smokers.

Methods

Immunohistochemistry, real-time PCR and western blot assays were used to systemically examine the spatial-, cell type- and isoform-specific expression of ACE2 in mouse brain and primary cultured brain cells. Experimental smoking exposure was conducted to evaluate the effect of smoking on brain expression.

Results

We observed ubiquitous expression of ACE2 but uneven brain distribution, with high expression in the cerebral microvasculature, medulla oblongata, hypothalamus, subventricular zones, and meninges around medulla oblongata and hypothalamus. Co-staining with cell type-specific markers demonstrates ACE2 is primarily expressed in astrocytes around the microvasculature, medulla oblongata, hypothalamus, ventricular and subventricular zones of cerebral ventricles, and subependymal zones in rhinoceles and rostral migratory streams, radial glial cells in the lateral ventricular zones, tanycytes in the third ventricle, epithelial cells and stroma in the cerebral choroid plexus, as well as cerebral pericytes, but rarely detected in neurons and cerebral endothelial cells. ACE2 expression in astrocytes is further confirmed in primary cultured cells. Furthermore, isoform-specific analysis shows astrocyte ACE2 has the peptidase domain responsible for SARS-CoV-2 entry, indicating astrocytes are indeed vulnerable to SARS-CoV-2 infection. Finally, our data show experimental tobacco smoking and electronic nicotine vaping exposure increase proinflammatory and/or immunomodulatory cytokine IL-1a, IL-6 and IL-5 without significantly affecting ACE2 expression in the brain, suggesting smoking may pre-condition a neuroinflammatory state in the brain.

Conclusions

The present study demonstrates a spatial- and cell type-specific expression of ACE2 in the brain, which might help to understand the acute and lasting post-infection neuropsychological manifestations in COVID-19 patients. Our data highlights a potential role of astrocyte ACE2 in the neural transmission and pathogenesis of COVID-19. This also suggests a pre-conditioned neuroinflammatory and immunocompromised scenario might attribute to exacerbated COVID-19 severity in the smokers.
Life threatening rupture of the diaphragm after Covid 19 pneumonia: a case report
Authors: Imamović Arvin , Wagner Doris , Lindenmann Jörg , Fink-Neuböck Nicole , Sauseng Siegfried , Bajric Tarik , Werkgartner Georg , Mischinger Hans Jörg
Published: June 2022

Background

The incidence of diaphragmatic rupture is low; however, it may be life threatening. Normally caused by blunt trauma, some cases are reported after pulmonary infections with extensive coughing. Covid 19 causes pulmonary infections and pneumonia and has been associated with weakening of the diaphragm after prolonged ventilation. We present a patient who suffered from diaphragmatic rupture 2 months after recovering from a severe Covid 19 pneumonia.

Case

A 71 years old male patient presented with massive thoraco-abdominal pain and severe dyspnea. At the time of admission, the patient was diagnosed with rupture of the diaphragm and developed cardiogenic shock. Intraoperatively there was a 4 cm diameter large rupture of the diaphragm with enterothorax (transverse colon, stomach, spleen, parts of the jejunum). Avulsion of the mesenteric arteries made a segmental resection of the jejunum together with the spleen necessary. A jejuno-jejunostomy was performed and organs were replaced into the abdomen. The rupture of the diaphragm underwent primary closure with non-resorbable suture material. The patient has shown an uneventful post-operative course, fully recovered and was discharged on day 11 after surgery.

Conclusion

Covid 19 is a disease that is known to have various effects on different organs. The diaphragm is only paid heed in case of dysfunction. Also in the setting of Covid 19 it is not known as prominent effector organ. Nevertheless its affection by coughing caused by Covid 19 can lead to life threatening complications.
The Amsterdam Foot Model: a clinically informed multi‐segment foot model developed to minimize measurement errors in foot kinematics
Authors: Schallig Wouter , van den Noort Josien C. , Piening Marjolein , Streekstra Geert J. , Maas Mario , van der Krogt Marjolein M. , Harlaar Jaap
Published: June 2022

Background

Foot and ankle joint kinematics are measured during clinical gait analyses with marker‐based multi‐segment foot models. To improve on existing models, measurement errors due to soft tissue artifacts (STAs) and marker misplacements should be reduced. Therefore, the aim of this study is to define a clinically informed, universally applicable multi‐segment foot model, which is developed to minimize these measurement errors.

Methods

The Amsterdam foot model (AFM) is a follow‐up of existing multi‐segment foot models. It was developed by consulting a clinical expert panel and optimizing marker locations and segment definitions to minimize measurement errors. Evaluation of the model was performed in three steps. First, kinematic errors due to STAs were evaluated and compared to two frequently used foot models, i.e. the Oxford and Rizzoli foot models (OFM, RFM). Previously collected computed tomography data was used of 15 asymptomatic feet with markers attached, to determine the joint angles with and without STAs taken into account. Second, the sensitivity to marker misplacements was determined for AFM and compared to OFM and RFM using static standing trials of 19 asymptomatic subjects in which each marker was virtually replaced in multiple directions. Third, a preliminary inter‐ and intra‐tester repeatability analysis was performed by acquiring 3D gait analysis data of 15 healthy subjects, who were equipped by two testers for two sessions. Repeatability of all kinematic parameters was assessed through analysis of the standard deviation (σ) and standard error of measurement (SEM).

Results

The AFM was defined and all calculation methods were provided. Errors in joint angles due to STAs were in general similar or smaller in AFM (≤2.9°) compared to OFM (≤4.0°) and RFM (≤6.7°). AFM was also more robust to marker misplacement than OFM and RFM, as a large sensitivity of kinematic parameters to marker misplacement (i.e. > 1.0°/mm) was found only two times for AFM as opposed to six times for OFM and five times for RFM. The average intra‐tester repeatability of AFM angles was σ:2.2[0.9°], SEM:3.3 ± 0.9° and the inter‐tester repeatability was σ:3.1[2.1°], SEM:5.2 ± 2.3°.

Conclusions

Measurement errors of AFM are smaller compared to two widely‐used multi‐segment foot models. This qualifies AFM as a follow‐up to existing foot models, which should be evaluated further in a range of clinical application areas.
An interventional quasi-experimental study to evaluate the impact of a rapid screening strategy in improving control of nosocomial extended-spectrum beta-lactamase-producing Enterobacterales and carbapenemase-producing organisms in critically ill patients
Authors: Martischang Romain , François Patrice , Cherkaoui Abdessalam , Renzi Gesuele , Fankhauser Carolina , Schrenzel Jacques , Pugin Jérôme , Harbarth Stephan
Published: June 2022

Introduction

Rapid molecular tests could accelerate the control of extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE) and carbapenemase-producing organisms (CPO) in intensive care units (ICUs).

Objective and methods

This interventional 12-month cohort study compared a loop-mediated isothermal amplification (LAMP) assay performed directly on rectal swabs with culturing methods (control period, 6 months), during routine ICU screening. Contact precautions (CP) were implemented for CPO or non-E. coli ESBL-producing Enterobacterales (nEcESBL-PE) carriers. Using survival analysis, we compared the time intervals from admission to discontinuation of unnecessary preemptive CP among patients at-risk and the time intervals from screening to implementation of CP among newly identified carriers. We also compared diagnostic performances, and nEcESBL-PE/CPO acquisition rates. This study is registered, ISRCTN 23588440.

Results

We included 1043 patients. During the intervention and control phases, 92/147 (62.6%) and 47/86 (54.7%) of patients at-risk screened at admission were candidates for early discontinuation of preemptive CP. The LAMP assay had a positive predictive value (PPV) of 44.0% and a negative predictive value (NPV) of 99.9% for CPO, and 55.6% PPV and 98.2% NPV for nEcESBL-PE. Due to result notification and interpretation challenges, the median time from admission to discontinuation of preemptive CP increased during the interventional period from 80.5 (95% CI 71.5–132.1) to 88.3 (95% CI 57.7–103.7) hours (p = 0.47). Due to the poor PPV, we had to stop using the LAMP assay to implement CP. No difference was observed regarding the incidence of nEcESBL-PE and CPO acquisition.

Conclusion

A rapid screening strategy with LAMP assays performed directly on rectal swabs had no benefit for infection control in a low-endemicity setting.
Dipeptidyl peptidase 4 inhibitor improves insulin resistance in Japanese patients with type 2 diabetes: a single-arm study, a brief report
Authors: Okura Tsuyoshi , Fujioka Yohei , Nakamura Risa , Ito Yuichi , Kitao Sonoko , Anno Mari , Matsumoto Kazuhisa , Shoji Kyoko , Okura Hiroko , Matsuzawa Kazuhiko , Izawa Shoichiro , Ueta Etsuko , Kato Masahiko , Imamura Takeshi , Taniguchi Shin-ichi , Yamamoto Kazuhiro
Published: June 2022

Background

Dipeptidyl peptidase 4 inhibitor (DPP4i) is an effective medicine for type 2 diabetes mellitus (T2DM). Some articles reported DPP4i improves insulin secretion and insulin resistance. However, these effects are not well established by glucose clamp test and test meal in Japanese. We investigated the effect of DPP4i on insulin resistance and insulin secretion by using the glucose clamp test and meal tolerance test (MTT).

Methods

We performed a MTT, and the hyperinsulinemic-euglycemic clamp in 8 Japanese patients with T2DM. This study was a single-arm study. We measured fasting and postprandial glucose, insulin, incretins, and glucagon levels. We also measured serum adiponectin levels.

Results

HbA1c was significantly decreased after 3 months. The fasting and postprandial glucose levels were significantly decreased. Fasting and postprandial insulin levels were not changed. The insulin resistance derived from the glucose clamp test was significantly improved. HOMA-IR was not significantly changed. GLP-1 and GIP were significantly increased but glucagon did not change. Adiponectin was not significantly changed.

Conclusions

Although the number of patients was very small, these results suggested that DPP4i treatment might improve insulin resistance without changing insulin secretion.
Klebsiella invasive liver abscess syndrome presenting with a central nervous system manifestation secondary to latent cholecystitis: a case report
Authors: Kinoshita Osamu , Okamoto Takanari , Ota Takayuki , Takayama Shun , Oi Yuta , Tanaka Sachie , Taniyama Ichita , Naito Kei , Inoue Yasuo
Published: June 2022

Background

Brain abscess is a life-threatening event. Moreover, when Klebsiella pneumoniae is the cause, rapid diagnosis and appropriate treatment are required. Klebsiella invasive liver abscess syndrome, a bloodstream metastatic infection of potentially aggressive nature, has been recognized to cause infection in the central nervous system, and concern for Klebsiella liver abscess syndrome is increasing globally.

Case presentation

A 73-year-old Japanese woman was admitted to the institution complaining of aggravated dysarthria and weakness in the right upper extremities with onset 5 days earlier. Magnetic resonance imaging revealed a brain abscess in the left basal ganglia, and abdominal computed tomography revealed a liver abscess in liver segment 7. The patient’s dysarthria symptoms became increasingly worse over the next few days, so surgical drainage via frontotemporal craniotomy was performed on admission day 3, and subsequent culture from the brain abscess showed growth of Klebsiella pneumoniae. On admission day 9, percutaneous transhepatic drainage of the liver segment 7 abscess was undertaken. The pus culture also showed growth of Klebsiella pneumoniae, thus associating the liver abscess with the brain abscess. Following long-term conservative treatment with antibiotics and abscess drainage, the liver abscess disappeared. However, the patient continuously presented with right upper quadrant pain, and abdominal computed tomography showed swelling of the gallbladder. Consequently, percutaneous transhepatic gallbladder drainage was initially administered, and the bile culture was also positive for Klebsiella pneumoniae. For radical treatment, a laparoscopic cholecystectomy was performed on admission day 99. The postoperative period was complicated by an intraabdominal abscess; however, conservative therapy was successful. She was subsequently discharged, and 12-month follow-up revealed no further sequelae.

Conclusions

We describe a rare case of Klebsiella liver abscess syndrome, which first presented with a central nervous system manifestation. Our patient was successfully treated via an early surgical intervention and subsequent antibiotic therapy. Although surgical drainage remains the cornerstone treatment for brain abscess, when a brain abscess is found, and there is a high index of suspicion for the existence of a liver abscess, Klebsiella liver abscess syndrome should be considered as a possible diagnosis.
The therapeutic effects of human embryonic stem cells-derived immunity-and-matrix regulatory cells on membranous nephropathy
Authors: Zhou Hui-song , Cui Zhao , Wang Hui , Gao Ting-ting , Wang Liu , Wu Jun , Xiong Zu-ying , Hao Jie , Zhao Ming-hui
Published: June 2022

Background

Primary membranous nephropathy (MN) is a kidney-specific autoimmune disease. Human embryonic stem cells-derived immunity-and-matrix regulatory cells (hESC-IMRCs) have immunoregulatory functions. We hypothesized that hESC-IMRCs might have therapeutic effects on MN and be a potential treatment in clinical practice.

Methods

Rats of Heymann nephritis were injected with sheep anti-rat Fx1A serum. hESC-IMRCs were intravenously administrated upon the detection of proteinuria, with 6 × 106 cells (high-dose) or 3 × 106 cells (low-dose) in 1 ml every other day. Splenocytes and IMRCs were co-cultured at different times and ratios. Cell types and cytokines were detected by flow cytometry and enzyme-linked immunosorbent assay.

Results

The urinary protein of rats with Heymann nephritis was reduced remarkably to a level comparable to negative controls, in both low-dose (45.6 vs. 282.3 mg/d, P < 0.001) and high-dose (35.2 vs. 282.3 mg/d, P < 0.001) hESC-IMRC treatment groups. IgG and C3 deposit, glomerular basement membrane thickness and foot process effacement were alleviated and the reduced podocin was recovered in the kidneys. The proportions of CD4 + CD25 + T cells in circulation and spleen were increased, and the circulating level of IL-10 was increased, after IMRC interventions. IL-17 and TNF-α were reduced after IMRCs treatments. IL-10 increased remarkably in the co-culture supernatant of lymphocytes and IMRCs at 48 h with ratio 10:1.

Conclusions

The intravenously delivered hESC-IMRCs alleviated proteinuria and kidney injuries of Heymann nephritis, by their immunosuppressive functions through regulatory T cells and IL-10. These pre-clinical results indicate that IMRCs worth careful consideration for human trials in the treatment of MN.
Comprehensive insight into endothelial progenitor cell-derived extracellular vesicles as a promising candidate for disease treatment
Authors: Chen Ke , Li Yang , Xu Luwei , Qian Yiguan , Liu Ning , Zhou Changcheng , Liu Jingyu , Zhou Liuhua , Xu Zheng , Jia Ruipeng , Ge Yu-Zheng
Published: June 2022

Endothelial progenitor cells (EPCs), which are a type of stem cell, have been found to have strong angiogenic and tissue repair capabilities. Extracellular vesicles (EVs) contain many effective components, such as cellular proteins, microRNAs, messenger RNAs, and long noncoding RNAs, and can be secreted by different cell types. The functions of EVs depend mainly on their parent cells. Many researchers have conducted functional studies of EPC-derived EVs (EPC-EVs) and showed that they exhibit therapeutic effects on many diseases, such as cardiovascular disease, acute kidney injury, acute lung injury, and sepsis. In this review article, we comprehensively summarized the biogenesis and functions of EPCs and EVs and the potent role of EPC-EVs in the treatment of various diseases. Furthermore, the current problems and future prospects have been discussed, and further studies are needed to compare the therapeutic effects of EVs derived from various stem cells, which will contribute to the accelerated translation of these applications in a clinical setting.
Estimating gap age using tree-ring width in combination with carbon isotope discrimination in a temperate forest, Northeast China
Authors: Yan Qiaoling , Zhu Chunyu , Zhu Jiaojun , Song Lining , Wang G. Geoff , Lu Deliang
Published: June 2022

Key message

The accuracy of gap age estimation can be improved from 5–6 to 2 years by analyzing the annual width and carbon isotope discrimination of the rings of gap-surrounding trees.

Context

Gap age has a direct link to the composition and structure of regeneration. However, the accuracy of gap age estimation is still limited.

Aim

We aim to improve the accuracy of gap age estimation by analyzing the width in combination with carbon isotope discrimination (∆13C) of the rings of gap-surrounding trees.

Methods

Twenty-four gap-surrounding trees (nine Ulmus laciniata, eight Fraxinus rhynchophylla, and seven Juglans mandshurica) were selected from eight artificial gaps created in December 2004. First, the growth release (i.e., peak time of percent growth change) for sample trees was measured based on the tree-ring width to identify the rough time range of gap formation. Then, the ∆13C of rings during the time range were analyzed for determining the precise year of gap formation.

Results

The peak time of percent growth change occurred from 2005 to 2010 for U. laciniata, 2004 to 2008 for F. rhynchophylla, and 2002 to 2007 for J. mandshurica. Within the range of 2002 to 2010, the ∆13C of rings for all sample trees significantly reduced in 2005–2006 (p < 0.05), which was the estimated year of gap formation.

Conclusion

The introduction of ∆13C analysis could effectively reduce the estimating deviations of gap age by only considering tree-ring width analyses and finally improve the accuracy of gap age estimation within 2 years, which can provide reliable information for gap management.
Optimal boundary control problems for a hierarchical age-structured two-species model
Authors: Liu Rong , Zhou Nan , He Ze-Rong
Published: June 2022

This paper discusses the optimal control problems for a nonlinear age-structured two-species model, where elder individuals are more competitive than younger ones, and each species is described by a nonlinear integropartial differential equation with a global feedback boundary condition. First, we establish the existence of a unique nonnegative bounded solution by means of frozen coefficients and the fixed-point theorem. More importantly, we discuss the least deviation-cost problem and the most benefit-cost problem. For the least deviation-cost problem, the existence of an optimal strategy is established by means of Ekeland’s variational principle, and the minimum principle is obtained via an adjoint system. Meanwhile, the corresponding results for the most benefit-cost problem are given. In addition, some numerical experiment results are presented to examine the effects of parameters on the optimal policies and indexes.
Correlation between dynamic changes in free triiodothyronine levels and 90-day prognosis in patients with HBV-related acute-on-chronic liver failure
Authors: Zhang Jian , Chen Yu , Ding Mei , Duan Zhongping
Published: June 2022

Background

Patients with HBV-related acute-on-chronic liver failure (HBV–ACLF) have a high 90-day mortality rate, so early prognostic evaluation is important.

Aim

We aimed to explore the correlation between dynamic changes in free triiodothyronine (FT3) levels and 90-day prognosis of patients with HBV–ACLF.

Methods

A prospective cohort study investigated 122 inpatients with HBV–ACLF. Patients were divided into three groups based on the dynamic change in FT3 level, as follows: continuous normal FT3; continuous decreased FT3; and FT3 U-shaped change groups, and patients were divided into survival group and non-survival group according to whether they were alive or not. The correlation between the change in FT3 level and 90-day prognosis was explored. Three factors that affected the prognosis most significantly were used to form an FT3 correlation formula to compare the difference in predicting prognosis between the formula score and the conventional score.

Results

There were 98 patients with decreased FT3 level (80.33%), and the lowest FT3 level was at 8.52 ± 6.38 days after admission, which lasted for 16 days. There were no significant differences in FT3 levels at admission and at the lowest point between the survival and non-survival groups. Cox regression analysis showed that the FT3 level, FT3 change type, and hepatic encephalopathy (HE) grading were important factors related to prognosis. The area under the receiver operating characteristics curve for the FT3 correlation formula score was 0.892, which was significantly higher than that of the CTP, MELD, MELD–Na, CLIF–SOFA, CLIF–C OF, and AARC scores (P < 0.001).

Conclusions

The FT3 level and its dynamic change type together with the HE grading can facilitate prediction of 90-day prognosis for patients with HBV–ACLF.
Modified dendritic cell-derived exosomes activate both NK cells and T cells through the NKG2D/NKG2D-L pathway to kill CML cells with or without T315I mutation
Authors: Du Zhuanyun , Huang Zhenglan , Chen Xi , Jiang Guoyun , Peng Yuhang , Feng Wenli , Huang Ningshu
Published: June 2022

Background

Tyrosine kinase inhibitors have achieved quite spectacular advances in the treatment of chronic myeloid leukemia (CML), but disease progression and drug resistance that related to the T315I mutation, remain major obstacles. Dendritic cell-derived exosomes (Dex) induce NK cell immunity, but have yet to achieve satisfactory clinical efficacy. An approach to potentiate antitumor immunity by inducing both NK- and T-cell activation is urgently needed. Retinoic acid early inducible-1γ (RAE-1γ), a major ligand of natural killer group 2 member D (NKG2D), plays an important role in NK-cell and T-lymphocyte responses. We generated RAE-1γ enriched CML-specific Dex (CML-RAE-1γ-Dex) from dendritic cells (DCs) pulsed with lysates of RAE-1γ-expressing CML cells or T315I-mutant CML cells, aiming to simultaneously activate NK cells and T lymphocytes.

Methods

We generated novel CML-RAE-1γ-Dex vaccines, which expressed RAE-1γ, and were loaded with CML tumor cell lysates. NK cells or T lymphocytes were coincubated with CML-RAE-1γ-Dex vaccines. Flow cytometry was performed to evaluate the activation and proliferation of these immune cells. Cytokine production and cytotoxicity toward CML cells with or without the T315I mutation were detected by ELISPOT, ELISA and LDH assays. CML models induced by BCR-ABL or BCR-ABLT315I were used to determine the immunological function of Dex in vivo.

Results

Herein, CML-RAE-1γ-Dex were prepared. CML-RAE-1γ-Dex effectively enhanced the proliferation and effector functions of NK cells, CD4+ T cells and CD8+ T cells, which in turn produced strong anti-CML efficacy in vitro. Moreover, CML-RAE-1γ-Dex-based immunotherapy inhibited leukemogenesis and generated durable immunological memory in CML mouse models. Similar immune responses were also observed with imatinib-resistant CML cells carrying the T315I mutation.

Conclusions

This approach based on CML-RAE-1γ-Dex vaccines may be a promising strategy for CML treatment, especially for cases with the T315I mutation.
Terminal anorexia nervosa is a dangerous term: it cannot, and should not, be defined
Authors: Guarda Angela S. , Hanson Annette , Mehler Philip , Westmoreland Patricia
Published: June 2022

A recent article (JED 10:23, 2022) proposed defining terminal anorexia to improve access to palliative and hospice care, and to medical aid in dying for a minority of patients with severe and enduring anorexia nervosa (SE-AN). The authors presented three cases and, for two, the first author participated in their death. Anorexia nervosa is a treatable psychiatric condition for which recovery may be uncertain. We are greatly concerned however regarding implications of applying the label “terminal” to anorexia nervosa and the risk it will lead to unjustified deaths in individuals whose mental illness impairs their capacity to make a reasoned treatment decision.
The effect of architecture design as the non-digital component to the digital industry development—case study ‘Brick Factory’ in Prishtina, Kosovo
Authors: Basha-Jakupi A. , Kuleta G. , Navakazi V.
Published: June 2022

Buildings that were once the machinery of production, and influencing not only the economic but also the social relations of the inhabitants, and while now those spaces remain 'dead,' it questions and at the same time strives for contemporary intervention to restore vitality and give more to the neighborhood. Neglected industrial facilities of the 'Brick Factory' in Prishtina will be the objective of this study. This research will attempt to give a new function to the current state of the building and its surroundings and new opportunities around it for the Kosovo young generation trying to fight the high unemployment and migration rates. Digital technologies have spread speedily in the world. In many instances, digital technologies have boosted growth, expanded opportunities, and improved services, and, at the same time, have provided an excellent basis for employment (World Bank, World development report 2016: digital dividends, World Bank, Washington, 2016). However, the advantages of digital technologies will be understood better when knowing how digital technology relates with other non-digital components, such as architecture, that are equally important for development. This study aims to connect them coherently and create a stimulating dialogue. Bringing the appropriate digital and non-digital components into the underdeveloped neighborhood enhances its inhabitant's economic development and social and emotional growth.
Corporate managers, price noise and the investment factor
Authors: Lehnert Thorsten
Published: June 2022

This study investigates the impact of flows between bond and equity funds on investment factors over the period 1984–2015. It determines contemporaneous mispricing effects and a statistical reversal relation between these flows and both legs of the investment factor. The statistical reversal relationship between previous flows and the investment factor is economically significant. A one-standard-deviation shock to flows causes a 0.29% decrease in investment factor returns, which are reversed within 5 months. A trading strategy based on signals from past flows and the investment factor outperforms the market by 0.68% in the months following positive flows and produces significant alphas after accounting for well-known equity risk factors. The findings are interpreted as evidence in favor of a behavioral explanation, in which sentiment influences actual managerial decisions. When retail investors and managers are swept up in market euphoria, retail investors shift their holdings from bond to equity mutual funds, and high-investment firms invest more aggressively. Market-level euphoria has a different impact on high- and low-investment firms, and thus the investment factor can be influenced. Hence, the mispricing occurs during these periods, and the reversal relationship is especially pronounced for a high-investment portfolio versus a low-investment portfolio. As a result, during the months following periods of positive flows, the investment factor outperforms the market factor. Interestingly, this study’s measure of flows, which serves as a proxy for market-level euphoria, outperforms other measures of investor sentiment.
Transnational gangs and criminal remittances: a conceptual framework
Authors: Paarlberg Michael Ahn
Published: June 2022

Policy responses to transnational criminal organizations (TCOs) within migrant receiving countries often conflate all organizations which conduct illegal activity in multiple countries based on the mafia or cartel model. This model imagines the TCO to be the most evolved form of organized crime: deeply institutionalized, well resourced, hierarchically structured, highly profitable, and diversified in their criminal activities. Such a model informs law enforcement and immigration policies which are often draconian and counterproductive to citizen security. In reality, transnational crime is highly varied in organization, activities, scope, and membership. A major TCO type that defies the mafia archetype is the transnational gang. This study seeks to nuance our understanding of TCOs, illustrated by case studies of two transnational gangs, MS-13 and Satudarah, by advancing the concept of criminal remittances to locate agency in transnationalization. As the case studies demonstrate, for transnational gangs, the remittance of criminal activity is not at the organization level but at the individual and state level. Thus the transnationalization of crime can itself be the product of state foreign and migration policies.
Effect of omega-three supplementation on serum urate and gout flares in people with gout; a pilot randomized trial
Authors: Stamp Lisa K. , Grainger Rebecca , Frampton Christopher , Drake Jill , Hill Catherine L.
Published: June 2022

Objectives

To determine the effect of omega-three supplementation with fish oil on serum urate, weight and body mass index (BMI) in people with gout.

Methods

A pilot 6-month, randomized, open-label clinical trial was undertaken in people with gout with serum urate ≥ 0.36 mmol/l. Forty participants were randomized to receive 6.2 g omega-3 fish oil daily or no fish oil for 24 weeks. Blood was obtained monthly for serum urate and red cell EPA (20:5n-3) DHA (22:6n-3) were measured using a blood spot collection system.

Results

There was no statistically significant difference in the mean (SEM) decrease in serum urate between baseline and week 24 between randomized groups: fish oil − 0.021 (0.02) mmol/l versus control − 0.006 (0.02) mmol/l. There was no significant difference in change in weight or BMI between baseline and week 24 between randomized groups. There was a statistically significant correlation between red cell omega-three concentrations and the total number of flares per participant between week 12 and week 24; total omega-three r =  − 0.75 (p ≤ 0.001), EPA r =  − 0.75 (p ≤ 0.001) and DHA r = -0.76 (p ≤ 0.001). In the omega-three fish oil group four participants reported gastrointestinal adverse effects definitely or probably related to the omega-three supplementation.

Conclusions

The lack of untoward effect of omega three fish oil supplementation on serum urate and BMI together with the relationship between higher omega-three concentrations and lower gout flares supports the development of further adequately powered clinical trials to determine the role of omega-three supplements as prophylaxis against gout flares in people starting urate lowering therapy.

Clinical trial registration ACTRN12617000539336p Registered 13/04/2017.
Impact of COVID-19 pandemic on the neurosurgical practice in Egypt
Authors: Nabil Mohamed , Dorrah Mohammed , Sharfeldin Asmaa , Abaza Hassan
Published: June 2022

Background

The COVID-19 pandemic and the subsequent lockdown have significantly altered many aspects of the health care services. We investigated the impact of the restrictive measures during the pandemic on the volume and spectrum of operated neurosurgical cases at two University hospitals in Egypt.

Results

The total number of surgeries dropped during the lockdown (second quarter of the year 2020) by 38%, compared with the total number of surgeries in the first quarter of the same year, with an increase in the proportion of urgent surgeries to the total number of surgeries from 46 to 69% (P < 0.001), and a decrease in the proportion of elective surgeries from the total number of neurosurgeries from 54 to 31% (P < 0.001). Similar differences were noted in the volume and spectrum of surgeries in the second quarter of 2020, when compared to the same period of the preceding year (2019).

Conclusions

The COVID-19 pandemic has significantly altered the nature and volume of neurosurgical practice. The overall number of surgeries showed a marked decline in the lockdown period; however, the numbers of urgent surgeries showed no significant difference under the lockdown.