bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-specific symptoms and post-treatment Lyme disease syndrome in patients with Lyme borreliosis: a prospective cohort study in Belgium (2016–2020)
Authors: Geebelen Laurence , Lernout Tinne , Devleesschauwer Brecht , Kabamba-Mukadi Benoît , Saegeman Veroniek , Belkhir Leïla , De Munter Paul , Dubois Bénédicte , Westhovens Rene ,   Humtick Hospital Group, Giot Jean-Baptiste , Léonard Philippe , Vangheluwe Riet , Wieërs Grégoire , Marot Jean-Christophe , Evrard Frédéric , Delaere Bénédicte , Noirhomme Séverine , Binnemans Els , Vanhoof Johan , Van Oyen Herman , Speybroeck Niko , Tersago Katrien
Published: September 2022

Background

Patients with Lyme borreliosis (LB) may report persisting non-specific symptoms such as fatigue, widespread musculoskeletal pain or cognitive difficulties. When present for more than 6 months and causing a reduction in daily activities, this is often referred to as post-treatment Lyme disease syndrome (PTLDS). This study aimed to compare the occurrence of symptoms between LB patients and controls, to estimate the proportion of LB patients developing PTLDS and to identify risk factors.

Methods

A prospective cohort study was set up including three subpopulations: patients with an erythema migrans (EM) (i) or disseminated/late LB (ii) and a non-LB control group (iii). At 6- and 12-months follow-up, the occurrence of several symptoms, including six symptoms used to define PTLDS, i.e. muscle pain, joint pain, fatigue, memory problems, difficulties concentrating and problems finding words, and impact on daily activities, was compared between LB patients and controls. Finally, the proportion of LB patients developing PTLDS as defined by the Infectious Disease Society of America was estimated, including a time frame for symptoms to be present.

Results

Although the risk of presenting PTLDS-related symptoms was significantly higher in EM patients (n = 120) compared to controls (n = 128) at 6 months follow-up, the risk of presenting at least one of these symptoms combined with impact on daily activities was not significantly higher in EM patients, at either 6- or 12-months follow-up. A significant association was found between disseminated/late LB (n = 15) and the occurrence of any PTLDS-symptom with an impact on daily activities at both time points. The proportion of patients with PTLDS was estimated at 5.9% (95% CI 2.7–12.9) in EM patients and 20.9% (95% CI 6.8–64.4) in patients with disseminated/late LB (RR = 3.53, 95% CI 0.98–12.68, p = 0.053). No significant risk factors were identified, which may be explained by small sample sizes.

Conclusions

In our study, PTLDS was present in both LB cohorts, yet with a higher percentage in disseminated/late LB patients. Additional research is needed into risk factors for and causes of this syndrome. In addition, development and validation of standardized methods to assess the PTLDS case definition, easily applicable in practice, is of great importance.
Association of human myxovirus resistance protein A with severity of COVID-19
Authors: Lehtinen Otto , Broman Niklas , Waris Matti , Vuorinen Tytti , Peltola Ville , Löyttyniemi Eliisa , Oksi Jarmo , Feuth Thijs
Published: September 2022

Background

In this retrospective cohort study, we explored the correlation of blood human myxovirus resistance protein A (MxA) level with severity of disease in hospitalized COVID-19 patients.

Methods

All 304 patients admitted for COVID-19 in our hospital until 30th of April 2021 were included in this study. MxA was measured from peripheral blood samples in 268 cases. Patients were divided into groups based on their level of MxA on admission. We studied baseline characteristics and severity of disease on admission based on clinical parameters and inflammatory biomarker levels in each group. Severity of disease during hospitalization was determined by the applied level of respiratory support, by the usage of corticosteroids and by the duration of hospitalization.

Results

Higher MxA levels on admission were associated with a shorter duration of symptoms before admission, and with more severe disease. Adjusted Odds Ratios for any respiratory support were 9.92 (95%CI 2.11–46.58; p = 0.004) in patients with MxA between 400 μg/L and 799 μg/L (p = 0.004) and 20.08 (95%CI 4.51–89.44; p < 0.001) in patients with MxA ≥ 800 μg/L in comparison with patients with initial MxA < 400 μg/L. The usage of corticosteroids was significantly higher in the high-MxA group (77%) in comparison with the intermediate-MxA group (62%, p = 0.013) and low-MxA group (47%, p < 0.001).

Conclusions

Higher initial levels of MxA were associated with more severe COVID-19. MxA may be a helpful additional biomarker to predict the severity of the disease.
Association between plasma cadmium and renal stone prevalence in adults in rural areas of Guangxi, China: a case–control study
Authors: Li You , He Kailian , Cao Liang , Tang Xu , Gou Ruoyu , Luo Tingyu , Xiao Song , Chen Ziqi , Li Tingjun , Qin Jian , Zhang Zhiyong , Cai Jiansheng
Published: September 2022

Background

Kidney stones have become a worldwide public health problem. The purpose of this research is to study the relationship between plasma cadmium level and the prevalence of kidney stones in an adult population.

Methods

The data of this study were based on a current survey conducted from December 2018 to November 2019 in Gongcheng Yao Autonomous County, Guangxi, China. A total of 940 study subjects of the same sex and age (within 2 years of each other) according to 1:1 matching were selected for a case–control study. The diagnosis of kidney stones was based on the presence of strong light spots, patches, clusters, or bands within the renal sinus region, followed by an echo-free bundle of acoustic images. Plasma metal elements were determined by the metal plasma method. The relationship between plasma cadmium concentration and the prevalence of kidney stones was assessed using logistic regression and restricted cubic spline regression.

Results

The crude ratio for kidney stones in the highest quartile of plasma cadmium was 1.164 (95% CI, 1.121 to 2.324) compared with the lowest quartile. A positive correlation was found between the two (P for trend = 0.039). After adjusting for potential confounders, the ratio of plasma cadmium to kidney stones in the highest quartile was 1.606 (95% CI, 1.100 to 2.344) compared with the lowest quartile, and the findings remained unchanged.

Conclusion

The odds of kidney stones in adults increased with increasing plasma cadmium exposure, and high plasma cadmium may be a risk factor for kidney stones.
“SpezPat”- common advance directives versus disease-centred advance directives: a randomised controlled pilot study on the impact on physicians’ understanding of non-small cell lung cancer patients’ end-of-life decisions
Authors: Koenig Julia Felicitas Leni , Asendorf Thomas , Simon Alfred , Bleckmann Annalen , Truemper Lorenz , Wulf Gerald , Overbeck Tobias R.
Published: September 2022

Background

The advance directive represents patients’ health care choices and fosters patients’ autonomy. Nevertheless, understanding patients’ wishes based on the information provided in advance directives remains a challenge for health care providers. Based on the ethical premises of positive obligation to autonomy, an advanced directive that is disease-centred and details potential problems and complications of the disease should help health care providers correctly understand patients’ wishes. To test this hypothesis, a pilot-study was conducted to investigate whether physicians could make the correct end-of-life decision for their patients when patients used a disease-centred advance directive compared to a common advance directive. 

Material and methods

A randomised, controlled, prospective pilot study was designed that included patients with non-small cell lung cancer (NSCLC) stage VI from the Department of Haematology and Medical Oncology, University Medical Centre, Goettingen. Patients were randomised into intervention and control groups. The control group received a common advance directive, and the intervention group received a disease-centred advance directive. Both groups filled out their advance directives and returned them. Subsequently, patients were asked to complete nine medical scenarios with different treatment decisions. For each scenario the patients had to decide whether they wanted to receive treatment on a 5-point Likert scale. Four physicians were given the same scenarios and asked to decide on the treatment according to the patients’ wishes as stated in their advance directives. The answers by patients and physicians were then compared to establish whether physicians had made the correct assumptions.

Results

Recruitment was stopped prior to reaching anticipated sample target. 15 patients with stage IV NSCLC completed the study, 9 patients were randomised into the control group and 6 patients in the intervention group. A total of 135 decisions were evaluated. The concordance between physicians’ and patients’ answers, was 0.83 (95%-CI 0.71–0.91) in the intervention group, compared to 0.60 (95%-CI 0.48–0.70) in the control group, and the difference between the two groups was statistically significant (p = 0.005).

Conclusion

This pilot study shows that disease-centred advance directives help physicians understand their NSCLC patients’ wishes more precisely and make treatment choices according to these wishes.

Trial registration

The study is registered at the German Clinical Trial Register (no. DRKS00017580, registration date 27/08/2019).
Erbin protects against sepsis-associated encephalopathy by attenuating microglia pyroptosis via IRE1α/Xbp1s-Ca2+ axis
Authors: Jing Guoqing , Zuo Jing , Fang Qing , Yuan Min , Xia Yun , Jin Qiyan , Liu Yuping , Wang Yanlin , Zhang Zongze , Liu Wanhong , Wu Xiaojing , Song Xuemin
Published: September 2022

Background

Microglia pyroptosis-mediated neuroinflammation is thought to be the crucial pathogenesis of sepsis-associated encephalopathy (SAE). Erbin has been reported to be associated with various inflammatory diseases. However, the role of Erbin in SAE and the relationship between Erbin and microglia pyroptosis are unknown. In this study, we investigated the promising role and underlying molecular mechanism of Erbin in the regulation of microglia pyroptosis.

Methods

WT and Erbin knockout mice underwent cecum ligation perforation (CLP) to induce SAE. Primary mouse microglia and BV2 cells were treated with LPS/nigericin in vitro. Behavioral tests were performed to evaluate cognitive function. Nissl staining and transmission electron microscopy were used to assess histological and structural lesions. ELISA and qPCR were carried out to detect neuroinflammation. Western blot and immunofluorescence were used to analyze protein expression. Flow cytometry and confocal microscopy were utilized to observe the Ca2+ changes in the cytoplasm and endoplasmic reticulum (ER). To further explore the underlying mechanism, STF083010 was administered to block the IRE1α/Xbp1s pathway.

Results

Erbin deletion resulted in more pronounced neuronal damage and cognitive impairment in mice that underwent CLP. Erbin knockout promoted microglial pyroptosis and inflammatory cytokines secretion in vivo and in vitro, which was mediated by activation of the IRE1α/Xbp1s. Treatment with the selective inhibitor STF083010 significantly inhibited IRE1α/Xbp1s pathway activity, decreased intracytoplasmic Ca2+, attenuated microglial pyroptosis, reduced pro-inflammatory cytokine secretion, lessened neuronal damage, and improved cognitive function.

Conclusions

In SAE, Erbin inhibits IRE1/Xbp1s pathway activity and reduces the ER Ca2+ influx to the cytoplasm, reducing microglial pyroptosis.
Determining optimal mobile neurofeedback methods for motor neurorehabilitation in children and adults with non-progressive neurological disorders: a scoping review
Authors: Behboodi Ahad , Lee Walker A. , Hinchberger Victoria S. , Damiano Diane L.
Published: September 2022

Background

Brain–computer interfaces (BCI), initially designed to bypass the peripheral motor system to externally control movement using brain signals, are additionally being utilized for motor rehabilitation in stroke and other neurological disorders. Also called neurofeedback training, multiple approaches have been developed to link motor-related cortical signals to assistive robotic or electrical stimulation devices during active motor training with variable, but mostly positive, functional outcomes reported. Our specific research question for this scoping review was: for persons with non-progressive neurological injuries who have the potential to improve voluntary motor control, which mobile BCI-based neurofeedback methods demonstrate or are associated with improved motor outcomes for Neurorehabilitation applications?

Methods

We searched PubMed, Web of Science, and Scopus databases with all steps from study selection to data extraction performed independently by at least 2 individuals. Search terms included: brain machine or computer interfaces, neurofeedback and motor; however, only studies requiring a motor attempt, versus motor imagery, were retained. Data extraction included participant characteristics, study design details and motor outcomes.

Results

From 5109 papers, 139 full texts were reviewed with 23 unique studies identified. All utilized EEG and, except for one, were on the stroke population. The most commonly reported functional outcomes were the Fugl-Meyer Assessment (FMA; n = 13) and the Action Research Arm Test (ARAT; n = 6) which were then utilized to assess effectiveness, evaluate design features, and correlate with training doses. Statistically and functionally significant pre-to post training changes were seen in FMA, but not ARAT. Results did not differ between robotic and electrical stimulation feedback paradigms. Notably, FMA outcomes were positively correlated with training dose.

Conclusion

This review on BCI-based neurofeedback training confirms previous findings of effectiveness in improving motor outcomes with some evidence of enhanced neuroplasticity in adults with stroke. Associative learning paradigms have emerged more recently which may be particularly feasible and effective methods for Neurorehabilitation. More clinical trials in pediatric and adult neurorehabilitation to refine methods and doses and to compare to other evidence-based training strategies are warranted.
A fatal case of viral sepsis and encephalitis in a child caused by human adenovirus type 7 infection
Authors: Zhao Hongwei , Liu Yingchao , Feng Ziheng , Feng Qianyu , Li Kechun , Gao Hengmiao , Qian Suyun , Xu Lili , Xie Zhengde
Published: September 2022

Adenoviruses are highly prevalent pathogens responsible for a wide range of clinical diseases, including respiratory tract infection, acute gastroenteritis, and conjunctivitis. However, adenovirus infection is rarely associated with central nervous system involvement. Here, we report a fatal viral sepsis and encephalitis in a child caused by a human adenovirus type 7 infection. We detected human adenovirus type 7 in the patient’s nasopharyngeal swab, blood, and cerebrospinal fluid. Our findings indicate clinicians should be aware of the possible central nervous system involvement in adenovirus infection.
Early identification of bleeding in trauma patients: external validation of traumatic bleeding scores in the Swiss Trauma Registry
Authors: Costa Alan , Carron Pierre-Nicolas , Zingg Tobias , Roberts Ian , Ageron François-Xavier ,   for the Swiss Trauma Registry
Published: September 2022

Background

Early identification of bleeding at the scene of an injury is important for triage and timely treatment of injured patients and transport to an appropriate facility. The aim of the study is to compare the performance of different bleeding scores.

Methods

We examined data from the Swiss Trauma Registry for the years 2015–2019. The Swiss Trauma Registry includes patients with major trauma (injury severity score (ISS) ≥ 16 and/or abbreviated injury scale (AIS) head ≥ 3) admitted to any level-one trauma centre in Switzerland. We evaluated ABC, TASH and Shock index (SI) scores, used to predict massive transfusion (MT) and the BATT score and used to predict death from bleeding. We evaluated the scores when used prehospital and in-hospital in terms of discrimination (C-Statistic) and calibration (calibration slope). The outcomes were early death within 24 h and the receipt of massive transfusion (≥ 10 Red Blood cells (RBC) units in the first 24 h or ≥ 3 RBC units in the first hour).

Results

We examined data from 13,222 major trauma patients. There were 1,533 (12%) deaths from any cause, 530 (4%) early deaths within 24 h, and 523 (4%) patients who received a MT (≥ 3 RBC within the first hour). In the prehospital setting, the BATT score had the highest discrimination for early death (C-statistic: 0.86, 95% CI 0.84–0.87) compared to the ABC score (0.63, 95% CI 0.60–0.65) and SI (0.53, 95% CI 0.50–0.56), P < 0.001. At hospital admission, the TASH score had the highest discrimination for MT (0.80, 95% CI 0.78–0.82). The positive likelihood ratio for early death were superior to 5 for BATT, ABC and TASH. The negative likelihood ratio for early death was below 0.1 only for the BATT score.

Conclusions

The BATT score accurately estimates the risk of early death with excellent performance, low undertriage, and can be used for prehospital treatment decision-making. Scores predicting MT presented a high undertriage rate. The outcome MT seems not appropriate to stratify the risk of life-threatening bleeding.

Trial registration: Clinicaltrials.gov, NCT04561050. Registered 15 September 2020.
Transcriptional signatures of the BCL2 family for individualized acute myeloid leukaemia treatment
Authors: Lee Chansub , Lee Sungyoung , Park Eunchae , Hong Junshik , Shin Dong-Yeop , Byun Ja Min , Yun Hongseok , Koh Youngil , Yoon Sung-Soo
Published: September 2022

Background

Although anti-apoptotic proteins of the B-cell lymphoma-2 (BCL2) family have been utilized as therapeutic targets in acute myeloid leukaemia (AML), their complicated regulatory networks make individualized therapy difficult. This study aimed to discover the transcriptional signatures of BCL2 family genes that reflect regulatory dynamics, which can guide individualized therapeutic strategies.

Methods

From three AML RNA-seq cohorts (BeatAML, LeuceGene, and TCGA; n = 451, 437, and 179, respectively), we constructed the BCL2 family signatures (BFSigs) by applying an innovative gene-set selection method reflecting biological knowledge followed by non-negative matrix factorization (NMF). To demonstrate the significance of the BFSigs, we conducted modelling to predict response to BCL2 family inhibitors, clustering, and functional enrichment analysis. Cross-platform validity of BFSigs was also confirmed using NanoString technology in a separate cohort of 47 patients.

Results

We established BFSigs labeled as the BCL2, MCL1/BCL2, and BFL1/MCL1 signatures that identify key anti-apoptotic proteins. Unsupervised clustering based on BFSig information consistently classified AML patients into three robust subtypes across different AML cohorts, implying the existence of biological entities revealed by the BFSig approach. Interestingly, each subtype has distinct enrichment patterns of major cancer pathways, including MAPK and mTORC1, which propose subtype-specific combination treatment with apoptosis modulating drugs. The BFSig-based classifier also predicted response to venetoclax with remarkable performance (area under the ROC curve, AUROC = 0.874), which was well-validated in an independent cohort (AUROC = 0.950). Lastly, we successfully confirmed the validity of BFSigs using NanoString technology.

Conclusions

This study proposes BFSigs as a biomarker for the effective selection of apoptosis targeting treatments and cancer pathways to co-target in AML.
Privacy-aware and Efficient Student Clustering for Sport Training with Hash in Cloud Environment
Authors: Diao Guoyan , Liu Fang , Zuo Zhikai , Moghimi Mohammad Kazem
Published: September 2022

With the wide adoption of health and sport concepts in human society, how to effectively analyze the personalized sports preferences of students based on past sports training records has become a crucial and emergent task with positive research significance. However, the past sports training records of students are often accumulated with time and stored in a central cloud platform and therefore, the data volume is too large to be processed with quick response. In addition, the past sports training records of students often contain certain sensitive information, which probably discloses partial user privacy if we cannot protect the data well. Considering these two challenges, a privacy-aware and efficient student clustering approach, named PESC is proposed, which is based on a hash technique and deployed on a central cloud platform connecting multiple local servers. Concretely, in the cloud platform, each student is firstly assigned an index based on the past sports training records stored in a local server, through a uniform hash mapping operation. Then similar students are clustered and registered in the cloud platform based on the students’ respective sport indexes. At last, we infer the personalized sport preferences of each student based on their belonged clusters. To prove the feasibility of PESC, we provide a case study and a set of experiments deployed on a time-aware dataset.
p53 amyloid aggregation in cancer: function, mechanism, and therapy
Authors: Li Jingzhi , Guo Ming , Chen Lin , Chen Zhuchu , Fu Ying , Chen Yongheng
Published: September 2022

Similar to neurodegenerative diseases, the concept that tumors are prion like diseases has been proposed in recent years. p53, the most well-known tumor suppressor, has been extensively studied for its expression, mutation, and function in various tumors. Currently, an interesting phenomenon of p53 prion-like aggregation has been found in several tumors, and studies have found that its pathological aggregation may lead to functional alterations and ultimately affect tumor progression. It has been demonstrated that the mechanism of p53 aggregation involves its mutation, domains, isoform, etc. In addition to p53 itself, some other factors, including Zn2+ concentration, pH, temperature and chaperone abnormalities, can also contribute to p53 aggregation. Although there are some studies about the mechanism and role of p53 aggregation and amyloidosis in tumors, there still exist some controversies. In this paper, we review the mechanism of p53 amyloid fibril structure and discuss the characteristics and effects of p53 amyloid aggregation, as well as the pathogenic mechanism leading to the occurrence of aggregation in tumors. Finally, we summarize the various inhibitors targeting p53 aggregation and prion-like behavior. In conclusion, a comprehensive understanding of p53 aggregation can expand our understanding of the causes leading its loss of physiological function and that targeting p53 aggregation might be a promising therapeutic strategy for tumor therapy.
Very small collars: an evaluation of telemetry location estimators for small mammals
Authors: Hummell Grace F. , Li Andrew Y. , Mullinax Jennifer M.
Published: September 2022

Background

Fine-scale tracking of animals such asPeromyscusspp. is still done with micro-very high frequency collars due to the animal’s small size and habitat usage. In most cases, tracking micro-very high frequency collars requires manual telemetry, yet throughout the literature, there is little reporting of individual telemetry methods or error reporting for small mammal spatial analyses. Unfortunately, there is even less documentation and consensus on the best programs used to calculate fine-scale animal locations from compass azimuths. In this study, we present a strategy for collecting fine-scale spatial data onPeromyscusspp.as a model species for micro-very high frequency collars and assess multiple programmatic options and issues when calculating telemetry locations.

Results

Mice were trapped from April to October 2018–2019 with Sherman traps in Howard County, Maryland, USA. Collars were placed on 61 mice, of which 31 were included in the analyses. We compared the two most cited location estimator programs in the literature, location of a signal software and Locate III, as well as the Sigloc package in program R. To assess the programmatic estimates of coordinates at a fine scale and examine programmatic impacts on different analyses, we created and compared minimum convex polygon and kernel density estimator home ranges from locations produced by each program. We found that 95% minimum convex polygon home range size significantly differed across all programs. However, we found more similarities in estimates across calculations of core home ranges. Kernel density estimator home ranges had similar patterns as the minimum convex polygon home ranges with significant differences in home range size for 95% and 50% contours. These differences likely resulted from different inclusion requirements of bearings for each program.

Conclusions

This study highlights how different location estimator programs could change the results of a small mammal study and emphasizes the need to calculate telemetry error and meticulously document the specific inputs and settings of the location estimator.
Cultural exchange and integration: archaeometallurgical case study on underneath-blade bronze dagger-axes from Shuangyuan Village Site in the Eastern Zhou Dynasty
Authors: Li Yuexuan , Yang Yingdong , Wang Tianyou , Wang Xiaoting , Luo Wugan
Published: September 2022

As typical artifacts of the Ba-Shu culture, bronze dagger-axes have always been highly valued by academia. Underneath-blade bronze dagger-axes were utilized widely in both the Central Plains and southwest China. However, opinions differ on whether these underneath-blade bronze dagger-axes which excavated from Ba-Shu culture were produced locally. Combined with archaeological typology study, p-XRF and MC-ICP-MS were used to analyze 12 underneath-blade bronze dagger-axes unearthed from Shuangyuan Village Site, an Eastern Zhou cemetery in Chengdu city, Sichuan Province, Southwest China in order to investigate the cultural exchange and integration centered on the Shu culture. The composition results show that the majority of samples were made from copper, tin, and lead ternary alloy. The data on lead isotopes indicate that underneath-blade bronze dagger-axes have different mineral sources. The lead isotope ratio 206Pb/204Pb of 18.3 can draw the conclusion to be used as one of the bases for judging that underneath-blade bronze dagger-axes originated in the Chengdu Plain or the Central Plains which was consistent with the typology. The southern China lead materials of underneath-blade bronze dagger-axes in the Ba-Shu and Central Plains style probably came from southern Sichuan; while the rest of underneath-blade bronze dagger-axes in the Central Plains style might use lead materials in the western Hunan-western Hubei area. The Shu culture which was represented by Shuangyuan Village Site in Chengdu Plain during the Eastern Zhou Dynasty had close cultural communication with the Central Plains and Chu cultures. This study reveals that Ba-Shu had a direct exchange of minerals or metal products with the Central Plains and Chu, as well as an imitation based on the identification of the foreign culture and the belief in the local Shu cultural traditions.
Multiple systemic artery to pulmonary vessel fistulas (SAPVFs) completely resected by video-assisted thoracoscopic surgery: a case report
Authors: Matsudo Kyoto , Haratake Naoki , Ono Yuki , Kohno Mikihiro , Takenaka Tomoyoshi , Yoshizumi Tomoharu
Published: September 2022

Background

Systemic artery to pulmonary vessel fistula (SAPVF) is an uncommon abnormal vascular communication between systemic arteries and the lung parenchyma. It has been reported that the appropriate treatment for SAPVF is embolization or surgical resection. However, in patients such as ours, who have many aberrant vessels or multiple lesions, surgery should be considered as the first-choice treatment.

Case presentation

This case report describes multiple SAPVFs and huge bullae at the apex of the left lung in a 43-year-old man that were resected completely with the video-assisted thoracoscopic surgery (VATS). The patient had an uneventful postoperative recovery without any complications and was discharged 9 days postoperatively. He had heavy smoking history, and the giant bullae and the diffuse emphysematous change were found in the lung. Therefore, the chronic inflammation may have been present in the thoracic cavity, which caused multiple SAPVFs.

Conclusions

We describe the clinical course and management of the patient with multiple SAPVFs who had no obvious history of surgery, trauma, or various inflammatory or infection diseases. VATS should be the first-choice treatment in patients with many abnormal vessels or multiple lesions.
Fund behavioral science like the frameworks we endorse: the case for increased funding of preliminary studies by the National Institutes of Health
Authors: Beets Michael W. , Pfledderer Christopher , von Klinggraeff Lauren , Burkart Sarah , Armstrong Bridget
Published: September 2022

Innovative, groundbreaking science relies upon preliminary studies (aka pilot, feasibility, proof-of-concept). In the behavioral sciences, almost every large-scale intervention is supported by a series of one or more rigorously conducted preliminary studies. The importance of preliminary studies was established by the National Institutes of Health (NIH) in 2014/2015 in two translational science frameworks (NIH Stage and ORBIT models). These frameworks outline the essential role preliminary studies play in developing the next generation of evidence-based behavioral prevention and treatment interventions. Data produced from preliminary studies are essential to secure funding from the NIH’s most widely used grant mechanism for large-scale clinical trials, namely the R01. Yet, despite their unquestionable importance, the resources available for behavioral scientists to conduct rigorous preliminary studies are limited. In this commentary, we discuss ways the existing funding structure at the NIH, despite its clear reliance upon high-quality preliminary studies, inadvertently discourages and disincentivizes their pursuit by systematically underfunding them. We outline how multiple complementary and pragmatic steps via a small reinvestment of funds from larger trials could result in a large increase in funding for smaller preliminary studies. We make the case such a reinvestment has the potential to increase innovative science, increase the number of investigators currently funded, and would yield lasting benefits for behavioral science and scientists alike.
Employment-related musculoskeletal complications experienced by the physical therapists in Bangladesh: a comprehensive cross-sectional case study
Authors: Hossain Amran , Proma Tasnuva Shamarukh , Raju Rashaduzzaman , Ahmed Sharmin , Islam Ariful
Published: September 2022

Background

Dentists, nurses, and physical therapists have all been associated with an increased risk of work-related diseases. The findings of studies in these different occupations might aid in the development of preventative measures. In Bangladesh, however, no comparable evidence has been recorded among physical therapists. The study’s goal was to find out the prevalence of work-related physical problems at different anatomical locations, as well as the link between these disorders and treatment strategies across Bangladeshi physical therapists.

Methods

A physical and online survey of Bangladeshi physical therapists was done. A total of 300 questionnaires were given out, with work-related discomfort or pain detected in nine locations of the body: (1) neck, (2) shoulder, (3) elbow, (4) wrists, (5) upper back, (6) lumbar, (7) thighs, (8) knee, and (9) ankle.

Results

85.5% of Bangladeshi physical therapists suffer musculoskeletal problems, according to the results of this research. The neck (25.7%), lower back (15.2%), elbow (12.3%), ankle (8.6%), and shoulder (8.6%) were the most often affected locations (7.1%). Upper back (3.0%) and hips (2.2%) ailments had the lowest prevalence.

Conclusion

Work-related musculoskeletal illnesses were common among the Bangladeshi physical therapists, especially in their neck, lower back, elbow, and ankle regions.
Monitoring of neutrophil priming in whole blood by antibodies isolated from a synthetic phage antibody library
Authors: Koenderman Leo , Kanters Deon , Maesen B , Raaijmakers Jan , Lammers Jan-Willem J , de Kruif John , Logtenberg Ton
Published: September 2022

Neutrophil activation is a multistep process. In vitro activation of neutrophils with semiphysiological activators is optimal only after preactivation or priming with cytokines, chemotaxins, and/or bacterial products. Until now, no antibodies have been developed that can distinguish between resting and (cytokine) primed neutrophils with a sufficient dynamic range necessary for screening clinical samples. We have isolated two human phage antibodies, designated MoPhab A17 and A27, from a synthetic bacteriophage antibody library. These phage antibodies recognize epitopes that are upregulated on neutrophils present in whole blood treated with low priming concentrations of cytokines, such as GM-CSF and TNF-α. This induction was time- and concentration-dependent and optimal at concentrations that are sufficient for priming functional responses in neutrophils: GM-CSF (10 pM) and TNF-α (100 IU/ml). PMNs, isolated from the peripheral blood of chronic obstructive pulmonary disease (COPD) patients with a clinical exacerbation, exhibited a partial in vivo primed phenotype. These antibodies promise to be an ideal tool to monitor disease activity in whole blood of patients with inflammatory diseases.
Innate and adaptive immunity in Candida albicans infections and saprophytism
Authors: Romani Luigina
Published: September 2022

Underlying acquired immunity to the fungus Candida albicans is usually present in adult immunocompetent individuals and is presumed to prevent mucosal colonization progressing to symptomatic infection. Exploration of immunological events leading to Candida resistance or susceptibility has indicated the central role of the innate and adaptive immune systems, the relative contribution of which may vary depending on the site of the primary infection. Nevertheless, acquired resistance to infection results from the development of Th1 responses. Cytokines produced by Th1 cells activate phagocytic cells to a candidacidal state. In contrast, cytokines produced by Th2 cells inhibit Th1 development and deactivate phagocytic effector cells. Because reciprocal influences have been recognized between innate and adaptive Th immunity, it appears that an integrated immune response determines the life-long commensalism of the fungus at the mucosal level, as well as the transition from mucosal saprophyte to pathogen.
HIV-1 can be recovered from a variety of cells including peripheral blood monocytes of patients receiving highly active antiretroviral therapy: a further obstacle to eradication
Authors: Crowe Suzanne M , Sonza Secondo
Published: September 2022

During highly active antiretroviral therapy (HAART), HIV-1 can still persist in circulating, resting CD4+ T lymphocytes, lymph node mononuclear cells, and seminal cells of patients despite sustained suppression of plasma viremia to undetectable levels. Sanctuary sites where antiretroviral drug penetration is not optimal may allow local HIV-1 infection of cells within and passing through these tissues. Factors such as imperfect drug adherence due to complicated drug regimens may also result in tissue compartments with suboptimal drug concentrations allowing viral replication. We have examined blood monocytes from HIV-1-infected subjects being effectively treated with HAART to determine virus carriage in these cells. Monocytes were purified from peripheral blood of patients with plasma HIV-1 RNA below 50 copies/mL and who had maintained levels of plasma RNA below detection for 3 months or more. Replication-competent virus could be recovered from the majority of monocyte populations by co-culture with CD8-depleted, PHA-activated, peripheral blood mononuclear cells. Sequencing of the reverse transcriptase and protease genes of the recovered viruses did not reveal resistance to both reverse transcriptase and protease inhibitors. Continued new infection of this transitory, circulating population of cells even during prolonged, effective HAART most likely reflects ongoing, low-level HIV-1 replication within cellular reservoirs and sanctuary sites in the body.
Osteopontin augments CD3-mediated interferon-γ and CD40 ligand expression by T cells, which results in IL-12 production from peripheral blood mononuclear cells
Authors: O’Regan Anthony W , Hayden Jason M , Berman Jeffrey S
Published: September 2022

Osteopontin is an RGD-containing bone matrix protein with cytokine-like functions that is associated with early stages of Th1-mediated diseases. Although the function of osteopontin in these responses is unknown, it is expressed by activated T cells and macrophages and can costimulate T cell proliferation. Studies have demonstrated that early IL-12 and IFN-γ expression is required to induce a protective response to many intracellular pathogens. Herein, we demonstrate that osteopontin stimulation augments the ability of anti-CD3 monoclonal antibody to induce CD40 ligand (CD40L) and IFN-γ expression on human T cells, resulting in CD40L- and IFN-γ-dependent IL-12 productionin vitro. These findings suggest a functional role for osteopontin in early Th1 responses, namely regulation of T cell-dependent IL-12 production. Further, osteopontin up-regulation of CD40L provides mechanistic support for the association of osteopontin with polyclonal B cell proliferation and humoral autoimmune disease.
Bleomycin-induced pulmonary fibrosis is independent of eosinophils
Authors: Hao Huiqing , Cohen Donald A , Jennings C Darrell , Bryson J Scott , Kaplan Alan M
Published: September 2022

Eosinophils have been shown to increase in tissues during many fibrotic conditions and consequently have been suggested to contribute to the development of fibrosis. This study tested the hypothesis that eosinophils are essential in the development of lung fibrosis in mice in response to bleomycin (BLM). Anti-IL-5 antibody was administered intraperitoneally into mice 2 h prior to endotracheal BLM inoculation and thereafter, every other day. Lung eosinophilia was evaluated by measurement of eosinophil peroxidase activity and confirmed by eosinophil counts in histologic sections. Lung fibrosis was evaluated by hydroxyproline content and confirmed by collagen staining in histological sections. Results demonstrated that BLM induced pronounced lung eosinophilia, which was maximal 7 days after BLM treatment and remained elevated through day 14, in C57Bl/6 SCID mice and CBA/J mice. In contrast, eosinophilia was a minor component in the lungs of wildtype C57Bl/6 mice after BLM treatment, although lung fibrosis developed similarly in all three strains of mice. Treatment with anti-IL-5 completely abrogated eosinophilia but failed to block pulmonary fibrosis induced by BLM in all mouse strains, including C57Bl/6 SCID, wildtype C57Bl/6 mice, and CBA/J mice. Analysis of cytokine mRNA by RNase-protection assay in C57Bl/6 SCID mice indicated that BLM treatment caused enhanced expression of the cytokines, TNF-α, and IL-6 at days 3, 7, and 14 post-BLM inoculation, regardless of whether eosinophils were depleted by anti-IL-5. Finally, the importance of eosinophils in lung fibrosis was examined in IL-5 gene knockout mice (IL-5tm1Kopf). BLM treatment induced significant lung fibrosis in IL-5 knockout mice in the absence of eosinophilia. These findings indicate that eosinophils are not an absolute requirement for BLM-induced pulmonary fibrosis in the mouse.
Dynamics of rab5 activation in endocytosis and phagocytosis
Authors: Roberts R L , Barbieri M A , Ullrich J , Stahl P D
Published: September 2022

Fluid-phase endocytosis is stimulated by H-ras-linked growth factor receptors and this stimulation requires activation of rab5. We utilized a GFP-rab5a:wt fusion protein to monitor GFP-rab5a:wt activation in living fibroblasts and in J774 macrophages. Control CHO cells that expressed GFP-rab5a:wt were cultured in serum-free conditions and showed GFP-rab5a:wt localized to endosomal vesicles with a mean diameter of 0.3 ± 0.1 μm. Endosome fusion, membrane ruffling, and pinosome formation were rarely detected in these cells. Coexpression of H-ras:G12V, a constitutively active H-ras mutant that activates rab5a, in cells resulted in marked enlargement of labeled endosomes (mean diameter 0.7 ± 0.2 μm) and large numbers of giant GFP-rab5a:wt-positive endosomes were present. Time-lapse recordings showed abundant fusion among giant labeled endosomes, and membrane ruffling and pinosome formation were commonly observed. Alterations in GFP-rab5a:wt endosome structure and activity in cells expressing H-ras:G12V were linked to rab5a activation because these changes were identical to those found in cells expressing GFP-rab5a:Q79L, a constitutively activated rab5a mutant. Furthermore, cells co-expressing H-ras:G12V and GFP-rab5a:S34N, an inactive rab5a mutant, exhibited no evidence of H-ras:G12V-induced endosome enlargement. To observe changes in endosome structure and activity that directly followed activation of GFP-rab5a:wt, we performed time-lapse recordings of cells cultured overnight in serum-free media after addition of EGF. EGF caused a rapid increase in endosome fusion and in membrane ruffling activity. Membrane ruffling was often associated with GFP-rab5a:wt-positive vesicle (pinosome) formation at the base of membrane ruffles. Endosome and pinosome fusion were common in EGF-stimulated cells. Phagocytosis is also regulated by GFP-rab5a:wt. J774 macrophages that expressed GFP-rab5a:wt showed transiently activation and recruitment of GFP-rab5a:wt to newly formed phagosomes that contained rhodamine-labeled Escherichia coli. These studies show that GFP-rab5a:wt activation results in dynamic alterations in the structure and activity of the early endosomal and early phagosomal elements.
Losartan, a selective inhibitor of subtype AT1 receptors for angiotensin II, inhibits neutrophil recruitment in the lung triggered by fMLP
Authors: Raiden Silvina , Pereyra Yanina , Nahmod Víctor , Alvarez Clarisa , Castello Liliana , Giordano Mirta , Geffner Jorge
Published: September 2022

We have shown that losartan, a selective inhibitor of AT1 receptors for angiotensin II (AII), inhibits the binding of [3H]fMLP to neutrophil receptors (FPR). Here, we analyze, in Wistar rats, the effect of losartan on neutrophil recruitment in the lung triggered by fMLP. We found that i.v. infusion of losartan (0.4–20.0 μg/kg/min) inhibits neutrophil recruitment induced by i.t. instillation of fMLP, without affecting the responses induced by other stimuli, such as aggregated human IgG (aIgG), precipitating immune complexes (IC), or zymosan. Histological evaluation of lungs as well as the analysis of lung hemorrhage indices showed that losartan prevents tissue injury partially in fMLP-challenged rats. We also analyzed the effect of losartan on lung-neutrophil recruitment triggered by i.t. instillation of Pseudomonas aeruginosa. Not only was there a marked decrease in neutrophil recruitment but also a significant increase in the survival of rats instillated with Pseudomonas aeruginosa, as a consequence of losartan treatment. Our results support the notion that losartan may be useful in the treatment of certain lung inflammatory disorders associated with bacterial infectious diseases.
Homotypic cluster formation of dendritic cells, a close correlate of their state of maturation. Defects in the biobreeding diabetes-prone rat
Authors: Delemarre Frans G A , Hoogeveen Patricia G , de Haan-Meulman Meeny , Simons Peter J , Drexhage Hemmo A
Published: September 2022

Aggregation of dendritic cells (DCs) in homotypic clusters has been described in vivo in lymph and skin, and here we report studies on homotypic clustering of rat splenic (s) DCs in vitro. Wistar rat sDCs readily formed homotypic clusters in culture, which increased in number and size over time (with a peak att = 3 h). Keeping the cells at higher densities or treatment with anti-CD43 induced more and larger homotypic clusters. After such enhanced clustering the DCs had increased their T cell stimulating capabilities in syngeneic mixed lymphocyte reaction, and had a higher expression of CD80 and CD86 (signs of maturation). Ag transfer from bovine serum albumin-fluorescein isothiocyanate-pulsed to unpulsed DCs was observed during clustering. Here we also show that sDCs of the biobreeding diabetes-prone (BB-DP) rat, a model of autoimmune diabetes/thyroiditis, formed fewer and smaller clusters than Wistar sDCs, and that DC-DC clustering resulted in only a modest maturation of the cells (as determined in syn MLR and by phenotyping). Anti-CD43 completely restored the clustering defect BB-DP DCs in vitro, yet T cell-stimulating capability was only restored to a limited extent. Ag transfer in BB-DP DC clusters was similar.
Protein kinase C θ is expressed in mast cells and is functionally involved in Fcɛ receptor I signaling
Authors: Liu Yin , Graham Caroline , Parravicini Valentino , Brown Martin J , Rivera Juan , Shaw Stephen
Published: September 2022

We investigated possible expression and function in mast cells ofprotein kinase C (PKC) θ, a member of the PKC family withdemonstrated function in a limited range of cell types. We found thatPKC θ is expressed in bone marrow-derived mast cells and in the RBL-2H3 mast cell line. PKC θ underwent translocation to the membranein response to Fcɛ receptor I (FcɛR I) activation. Receptoractivation induced phosphorylation of PKC θ. The tyrosinephosphorylation of PKC θ is delayed relative to PKC δ and coincidestemporally with PKC θ association with c-src family members Lyn andSrc. Studies of RBL-2H3 cells transduced with PKC θ constructsindicated a role for PKC θ in receptor-induced activation ofextracellular regulated kinases, interleukin-3 gene transcription, anddegranulation in response to antigen stimulation. These studies extendthe known functions of PKCθ to another important immune cell type andindicate the concurrent participation of multiple PKCs in the FcɛRI-mediated response of mast cells.
Different Toll-like receptor agonists induce distinct macrophage responses
Authors: Jones Bryan W , Means Terry K , Heldwein Kurt A , Keen Marc A , Hill Preston J , Belisle John T , Fenton Matthew J
Published: September 2022

We previously reported that gram-negative bacterial lipopolysaccharide (LPS) activates cells via Toll-like receptor (TLR) 4, whereas the mycobacterial cell wall glycolipid lipoarabinomannan (LAM) activates cells via TLR2. We also identified a secreted TLR2 agonist activity in short-term culture filtrates of Mycobacterium tuberculosis bacilli, termed soluble tuberculosis factor (STF). Here we show that STF contains mannosylated phosphatidylinositol (PIM) and that purified PIM possesses TLR2 agonist activity. Stimulation of RAW 264.7 macrophages by LPS, LAM, STF, and PIM rapidly activated nuclear factor (NF)-κB, activator protein-1 (AP-1), and mitogen-activated protein (MAP) kinases. These TLR agonists induced similar levels of NF-κB and AP-1 DNA-binding activity, as well as trans-activation function. Unexpectedly, these TLR agonists induced tumor necrosis factor α secretion, whereas only LPS was capable of inducing interleukin-1β and nitric oxide secretion. Thus, different TLR proteins are still capable of activating distinct cellular responses, in spite of their shared capacities to activate NF-κB, AP-1, and MAP kinases.