bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractOver 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

Abstract
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

Abstract
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

Abstract
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

AbstractBackgroundFoot 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.MethodsThe 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).ResultsThe 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°.ConclusionsMeasurement 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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

AbstractEndothelial 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

Abstract
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.