bluuebunny/crossref_metadata_2025 huggingface dataset:
The real-world outcomes of vedolizumab in patients with ulcerative colitis in Korea: a multicenter retrospective study
Authors: Ye Byong Duk , Cheon Jae Hee , Song Ki Hwan , Kim Joo Sung , Kim Young-Ho , Yoon Hyuk , Lee Kang-Moon , Kang Sang-Bum , Jang Byung Ik , Park Jae Jun , Kim Tae Oh , Lee Dae-Wook , Foo Chee Yoong , Shin Jeong Eun , Park Dong Il
Published: July 2021

Aim:

This study examined the real-world effectiveness and safety outcomes of vedolizumab in ulcerative colitis (UC) patients who had failed anti-tumor necrosis factor (anti-TNF) therapy in Korea.

Methods:

A retrospective chart review study was conducted in adults with moderate to severely active UC who had failed anti-TNF agents and subsequently received vedolizumab. Clinical response and clinical remission at week 6 and 14 after vedolizumab initiation was evaluated. Safety outcomes were also reported. Outcome rates were compared with a matched sub-cohort derived from the open-label sub-cohort of the GEMINI 1 trial using the optimal matching method.

Results:

A total of 105 patients (mean age, 45.3 years; 63.8% male) were included. At week 6, 55.8% ( n = 43/77) achieved a clinical response and 18.2% ( n = 14/77) achieved clinical remission. At week 14, 73.2% ( n = 52/71) achieved a clinical response and 39.4% ( n = 28/71) achieved clinical remission. When non-response imputation was used, the clinical response rate at week 6 and week 14 were 40.1% ( n = 43/105) and 49.5% ( n = 52/105) respectively. Of the 105 patients, 16 (15.2%) experienced at least one adverse event. The matched analysis showed that the clinical response rate at week 6 was higher in the matched sub-cohort of this study (24/47, 51.1%) versus the matched sub-cohort from the GEMINI 1 open-label cohort (12/47, 34.3%, p = 0.019). The clinical remission rates at week 6 were similar (7/47, 14.9% versus 9/47, 19.1%, p = 0.785).

Conclusions:

In the real-world setting, vedolizumab is effective and well tolerated within the first 14 weeks of use in Korea. The proportion of patients experiencing clinical response and clinical remission at 6 and 14 weeks appeared to be largely consistent with that observed in real-world studies from other regions and populations.
Service Priority Climate and Service Performance Among Hospitality Employees: The Role of Emotional Labor and Workload Pressure
Authors: Vashdi Dana R. , Katz–Navon Tal , Delegach Marianna
Published: July 2021

Frontline hotel employees face a complex organizational environment that constantly makes multiple demands, creating a persistent trade-off between service as a key element of the organization’s strategy and other competing or even conflicting goals. This study proposes an integrated and unique way of discerning the relationship between service climate and service performance through the prism of surface and deep acting emotional labor and suggests a new dimension of the service climate—the service priority climate. Specifically, we examined employees’ use of emotional labor strategies as a mechanism that explains the relationship between service priority climate and service performance. We also investigated whether workload pressure influences this relationship. Using a multilevel, multisource study, we surveyed a sample of 245 hotel employees working in 39 departments and their direct managers. The results demonstrated that when employees regarded service as a priority compared with other competing goals, they used more deep acting emotional labor strategies, resulting in better service performance. However, this was apparent only when workload pressure was low. Implications for hospitality organizations are discussed.
Brecciation, post-geographies, and spaces in transition
Authors: Bartolini Nadia
Published: July 2021

This commentary on Myriam Houssay-Holzschuch’s article, ‘Keeping You Post-ed: Space-Time Regimes, Metaphors, and Post-Apartheid’, focuses on two aspects. First, I expand on the metaphor of brecciation and how it can shine a light on processes that are still becoming – extending time and spatial configurations as variegated elements in a whole. Second, I want to build on the author’s reflection of tracking space-time regimes by considering how being ‘in the midst of transition’ interferes with preconceived timelines of what it means to be pre and post, and displays hidden processes as spatial configurations unfold.
Recurrent Priapism From Cabergoline and Bromocriptine in a Hypogonadal Man With Prolactinoma
Authors: Menon Lakshmi P. , Rahman Wedad
Published: July 2021

Dopamine agonists are generally well tolerated and represent the first-line therapy for prolactinomas. We report a case of a 20-year-old man with a macroprolactinoma who developed recurrent priapism with cabergoline and bromocriptine. Transsphenoidal pituitary adenoma resection was done with normalization of the prolactin level. Priapism is a rare side effect of dopamine agonists that warrants discontinuation of therapy. Patients should be educated about this potential side effect at the time of prescribing the medication.
Stock-Trading Simulations as a Resource for Management Instructors
Authors: Pierce Jason R.
Published: July 2021

This article reviews stock-trading simulations as a resource for use in management courses. Stock-trading simulations have three highly desirable qualities for educators: (1) they cost nothing to use—instructors can choose from various free simulators that all have the same general functionality, (2) they provide real and continuously updating data (e.g., company news, stock price movements), and (3) they can be customized to enhance learning. Feedback from experience, colleagues, and students confirms that all stock-trading simulations can indirectly enrich learning in courses, such as principles of management and strategy, by compelling students to follow and analyze the decisions of corporate managers. Stock-trading simulations also provide opportunities for students in courses covering managerial decision making to directly analyze and learn from their own decisions when they trade virtual shares of companies. The review concludes with a summary of the potential strengths and limitations management instructors should consider before implementing stock-trading simulations.
Smart as (un)democratic? The making of a smart city imaginary in Kolkata, India
Authors: Ghosh Bipashyee , Arora Saurabh
Published: July 2021

‘Smart’ imaginaries have been enthusiastically embraced by urban planners and policymakers around the world. Indians are no exception. Between 2015–2018, following national government guidelines to use participatory and inclusive processes, many cities developed proposals for a smart city challenge. Successful proposals received financial and technical support from the national government. We examine the making of the smart city proposal submitted by New Town Kolkata (NTK). We ask how (un)democratic was the making of the proposal, along three aspects: distributive, participatory, and responsive. Based on an analysis of documents and interviews with policymakers and citizens, we find that NTK’s smart city imaginary largely failed to be distributive. It rarely accounted for the specific needs of poorer and vulnerable citizens. City officials invested considerable effort in using participatory techniques, but citizen participation was tightly controlled through top-down design and practice of the techniques. The latter often facilitated one-way flow of information from the city administration to the citizens. The proposal was responsive to some citizens’ voices, but only those belonging to the more affluent classes. A messy diversity of citizens’ voices was thus closed down, as the city officials filtered and cherry-picked citizens’ voices that were well-aligned with the official technocratic vision of ‘global’ smart urbanism. The paper shows how democracy can be put in the service of technocracy, within a rhetoric of citizen participation and social inclusion that embodies smart urbanism.
Surface Integrity of Ultrasonically-Assisted Milled Ti6Al4V Alloy Manufactured by Selective Laser Melting
Authors: Guo Sai , Du Wei , Jiang Qinghong , Dong Zhigang , Zhang Bi
Published: July 2021

The Ti6Al4V parts produced by the existing selective laser melting (SLM) are mainly confronted with poor surface finish and inevitable interior defects, which substantially deteriorates the mechanical properties and performances of the parts. In this regard, ultrasonically-assisted machining (UAM) technique is commonly introduced to improve the machining quality due to its merits in increasing tool life and reducing cutting force. However, most of the previous studies focus on the performance of UAM with ultrasonic vibrations applied in the tangential and feed directions, whereas few of them on the impact of ultrasonic vibration along the vertical direction. In this study, the effects of feed rate on surface integrity in ultrasonically-assisted vertical milling (UAVM) of the Ti6Al4V alloy manufactured by SLM were systemically investigated compared with the conventional machining (CM) method. The results revealed that the milling forces in UAVM showed a lower amplitude than that in CM due to the intermittent cutting style. The surface roughness values of the parts produced by UAVM were generally greater than that by CM owing to the extra sinusoidal vibration textures induced by the milling cutter. Moreover, the extra vertical ultrasonic vibration in UAVM was beneficial to suppressing machining chatter. As feed rate increased, surface microhardness and thickness of the plastic deformation zone in CM raised due to more intensive plastic deformation, while these two material properties in UAVM were reduced owing to the mitigated impact effect by the high-frequency vibration of the milling cutter. Therefore, the improved surface microhardness and reduced thickness of the subsurface deformation layer in UAVM were ascribed to the vertical high-frequency impact of the milling cutter in UAVM. In general, the results of this study provided an in-depth understanding in UAVM of Ti6Al4V parts manufactured by SLM.
HOME-BIO (sHOtgun MEtagenomic analysis of BIOlogical entities): a specific and comprehensive pipeline for metagenomic shotgun sequencing data analysis
Authors: Ferravante Carlo , Memoli Domenico , Palumbo Domenico , Ciaramella Paolo , Di Loria Antonio , D’Agostino Ylenia , Nassa Giovanni , Rizzo Francesca , Tarallo Roberta , Weisz Alessandro , Giurato Giorgio
Published: July 2021

Background

Next-Generation-Sequencing (NGS) enables detection of microorganisms present in biological and other matrices of various origin and nature, allowing not only the identification of known phyla and strains but also the discovery of novel ones. The large amount of metagenomic shotgun data produced by NGS require comprehensive and user-friendly pipelines for data analysis, that speed up the bioinformatics steps, relieving the users from the need to manually perform complex and time-consuming tasks.

Results

We describe here HOME-BIO (sHOtgun MEtagenomic analysis of BIOlogical entities), an exhaustive pipeline for metagenomics data analysis, comprising three independent analytical modules designed for an inclusive analysis of large NGS datasets.

Conclusions

HOME-BIO is a powerful and easy-to-use tool that can be run also by users with limited computational expertise. It allows in-depth analyses by removing low-complexity/ problematic reads, integrating the analytical steps that lead to a comprehensive taxonomy profile of each sample by querying different source databases, and it is customizable according to specific users’ needs.
Plasticity in plastid redox networks: evolution of glutathione-dependent redox cascades and glutathionylation sites
Authors: Müller-Schüssele Stefanie J. , Bohle Finja , Rossi Jacopo , Trost Paolo , Meyer Andreas J. , Zaffagnini Mirko
Published: July 2021

Background

Flexibility of plant metabolism is supported by redox regulation of enzymes via posttranslational modification of cysteine residues, especially in plastids. Here, the redox states of cysteine residues are partly coupled to the thioredoxin system and partly to the glutathione pool for reduction. Moreover, several plastid enzymes involved in reactive oxygen species (ROS) scavenging and damage repair draw electrons from glutathione. In addition, cysteine residues can be post-translationally modified by forming a mixed disulfide with glutathione (S-glutathionylation), which protects thiol groups from further oxidation and can influence protein activity. However, the evolution of the plastid glutathione-dependent redox network in land plants and the conservation of cysteine residues undergoing S-glutathionylation is largely unclear.

Results

We analysed the genomes of nine representative model species from streptophyte algae to angiosperms and found that the antioxidant enzymes and redox proteins belonging to the plastid glutathione-dependent redox network are largely conserved, except for lambda- and the closely related iota-glutathione S-transferases. Focussing on glutathione-dependent redox modifications, we screened the literature for target thiols of S-glutathionylation, and found that 151 plastid proteins have been identified as glutathionylation targets, while the exact cysteine residue is only known for 17% (26 proteins), with one or multiple sites per protein, resulting in 37 known S-glutathionylation sites for plastids. However, 38% (14) of the known sites were completely conserved in model species from green algae to flowering plants, with 22% (8) on non-catalytic cysteines. Variable conservation of the remaining sites indicates independent gains and losses of cysteines at the same position during land plant evolution.

Conclusions

We conclude that the glutathione-dependent redox network in plastids is highly conserved in streptophytes with some variability in scavenging and damage repair enzymes. Our analysis of cysteine conservation suggests that S-glutathionylation in plastids plays an important and yet under-investigated role in redox regulation and stress response.
An illuminated respiratory activity monitoring system identifies priming-active compounds in plant seedlings
Authors: Loogen Judith , Müller André , Balzer Arne , Weber Sophie , Schmitz Kathrin , Krug Roxanne , Schaffrath Ulrich , Pietruszk Jörg , Conrath Uwe , Büchs Jochen
Published: July 2021

Background

Growing large crop monocultures and heavily using pesticides enhances the evolution of pesticide-insensitive pests and pathogens. To reduce pesticide use in crop cultivation, the application of priming-active compounds (PrimACs) is a welcome alternative. PrimACs strengthen the plant immune system and could thus help to protect plants with lower amounts of pesticides. PrimACs can be identified, for example, by their capacity to enhance the respiratory activity of parsley cells in culture as determined by the oxygen transfer rate (OTR) using the respiration activity monitoring system (RAMOS) or its miniaturized version, µRAMOS. The latter was designed for with suspensions of bacteria and yeast cells in microtiter plates (MTPs). So far, RAMOS or µRAMOS have not been applied to adult plants or seedlings, which would overcome the limitation of (µ)RAMOS to plant suspension cell cultures.

Results

In this work, we introduce a modified µRAMOS for analysis of plant seedlings. The novel device allows illuminating the seedlings and records the respiratory activity in each well of a 48-well MTP. To validate the suitability of the setup for identifying novel PrimAC in Arabidopsis thaliana, seedlings were grown in MTP for seven days and treated with the known PrimAC salicylic acid (SA; positive control) and the PrimAC candidate methyl 1-(3,4-dihydroxyphenyl)-2-oxocyclopentane-1-carboxylate (Tyr020). Twenty-eight h after treatment, the seedlings were elicited with flg22, a 22-amino acid peptide of bacterial flagellin. Upon elicitation, the respiratory activity was monitored. The evaluation of the OTR course reveals Tyr020 as a likely PrimAC. The priming-inducing activity of Tyr020 was confirmed using molecular biological analyses in A. thaliana seedlings.

Conclusion

We disclose the suitability of µRAMOS for identifying PrimACs in plant seedlings. The difference in OTR during a night period between primed and unprimed plants was distinguishable after elicitation with flg22. Thus, it has been shown that the µRAMOS device can be used for a reliable screening for PrimACs in plant seedlings.
The burden of hand, foot, and mouth disease among children under different vaccination scenarios in China: a dynamic modelling study
Authors: Liu Zhixi , Tian Jie , Wang Yue , Li Yixuan , Liu-Helmersson Jing , Mishra Sharmistha , Wagner Abram L. , Lu Yihan , Wang Weibing
Published: July 2021

Background

Hand, foot, and mouth disease (HFMD) is a common illness in young children. A monovalent vaccine has been developed in China protecting against enterovirus-71, bivalent vaccines preventing HFMD caused by two viruses are under development.

Objective

To predict and compare the incidence of HFMD under different vaccination scenarios in China.

Methods

We developed a compartmental model to capture enterovirus transmission and the natural history of HFMD in children aged 0–5, and calibrated to reported cases in the same age-group from 2015 to 2018. We compared the following vaccination scenarios: different combinations of monovalent and bivalent vaccine; a program of constant vaccination to that of pulse vaccination prior to seasonal outbreaks.

Results

We estimate 1,982,819, 2,258,846, 1,948,522 and 2,398,566 cases from 2015 to 2018. Increased coverage of monovalent vaccine from 0 to 80% is predicted to decrease the cases by 797,262 (49.1%). Use of bivalent vaccine at an 80% coverage level would decrease the cases by 828,560. Use of a 2.0× pulse vaccination for the bivalent vaccine in addition to 80% coverage would reduce cases by over one million. The estimated R0 for HFMD in 2015–2018 was 1.08, 1.10, 1.35 and 1.17.

Conclusions

Our results point to the benefit of bivalent vaccine and using a pulse vaccination in specific months over routine vaccination. Other ways to control HFMD include isolation of patients in the early stage of dissemination, more frequent hand-washing and ventilation, and better treatment options for patients.
Sex-based clinical and immunological differences in COVID-19
Authors: Huang Bin , Cai Yun , Li Ning , Li Kening , Wang Zhihua , Li Lu , Wu Lingxiang , Zhu Mengyan , Li Jie , Wang Ziyu , Wu Min , Li Wanlin , Wu Wei , Zhang Lishen , Xia Xinyi , Wang Shukui , Chen Hongshan , Wang Qianghu
Published: July 2021

Background

Males and females differ in their immunological responses to foreign pathogens. However, most of the current COVID-19 clinical practices and trials do not take the sex factor into consideration.

Methods

We performed a sex-based comparative analysis for the clinical outcomes, peripheral immune cells, and severe acute respiratory syndrome coronavirus (SARS-CoV-2) specific antibody levels of 1558 males and 1499 females COVID-19 patients from a single center. The lymphocyte subgroups were measured by Flow cytometry. The total antibody, Spike protein (S)-, receptor binding domain (RBD)-, and nucleoprotein (N)- specific IgM and IgG levels were measured by chemiluminescence.

Results

We found that male patients had approximately two-fold rates of ICU admission (4.7% vs. 2.7% in males and females, respectively,P = 0.005) and mortality (3% vs. 1.4%, in males and females, respectively,P = 0.004) than female patients. Survival analysis revealed that the male sex is an independent risk factor for death from COVID-19 (adjusted hazard ratio [HR] = 2.22, 95% confidence interval [CI]: 1.3–3.6,P = 0.003). The level of inflammatory cytokines in peripheral blood was higher in males during hospitalization. The renal (102/1588 [6.5%] vs. 63/1499 [4.2%], in males and females, respectively,P = 0.002) and hepatic abnormality (650/1588 [40.9%] vs. 475/1499 [31.7%],P = 0.003) were more common in male patients than in female patients. By analyzing dynamic changes of lymphocyte subsets after symptom onset, we found that the percentage of CD19+ B cells and CD4+ T cells was generally higher in female patients during the disease course of COVID-19. Notably, the protective RBD-specific IgG against SARS-CoV-2 sharply increased and reached a peak in the fourth week after symptom onset in female patients, while gradually increased and reached a peak in the seventh week after symptom onset in male patients.

Conclusions

Males had an unfavorable prognosis, higher inflammation, a lower percentage of lymphocytes, and indolent antibody responses during SARS-CoV-2 infection and recovery. Early medical intervention and close monitoring are important, especially for male COVID-19 patients.
Hepatic cysteine sulphinic acid decarboxylase depletion and defective taurine metabolism in a rat partial nephrectomy model of chronic kidney disease
Authors: Abbasian Nima , Ghaderi-Najafabadi Maryam , Watson Emma , Brown Jeremy , Yu si Li , Bursnall Debbie , Pawluczyk Izabella , Seymour Anne-Marie , Bevington Alan
Published: July 2021

Background

Taurine depletion occurs in patients with end-stage chronic kidney disease (CKD). In contrast, in the absence of CKD, plasma taurine is reported to increase following dietary L-glutamine supplementation. This study tested the hypothesis that taurine biosynthesis decreases in a rat CKD model, but is rectified by L-glutamine supplementation.

Methods

CKD was induced by partial nephrectomy in male Sprague-Dawley rats, followed 2 weeks later by 2 weeks of 12% w/w L-glutamine supplemented diet (designated NxT) or control diet (NxC). Sham-operated control rats (S) received control diet.

Results

Taurine concentration in plasma, liver and skeletal muscle was not depleted, but steady-state urinary taurine excretion (a measure of whole-body taurine biosynthesis) was strongly suppressed (28.3 ± 8.7 in NxC rats versus 78.5 ± 7.6 μmol/24 h in S, P < 0.05), accompanied by reduced taurine clearance (NxC 0.14 ± 0.05 versus 0.70 ± 0.11 ml/min/Kg body weight in S, P < 0.05). Hepatic expression of mRNAs encoding key enzymes of taurine biosynthesis (cysteine sulphinic acid decarboxylase (CSAD) and cysteine dioxygenase (CDO)) showed no statistically significant response to CKD (mean relative expression of CSAD and CDO in NxC versus S was 0.91 ± 0.18 and 0.87 ± 0.14 respectively). Expression of CDO protein was also unaffected. However, CSAD protein decreased strongly in NxC livers (45.0 ± 16.8% of that in S livers, P < 0.005). L-glutamine supplementation failed to rectify taurine biosynthesis or CSAD protein expression, but worsened CKD (proteinuria in NxT 12.5 ± 1.2 versus 6.7 ± 1.5 mg/24 h in NxC, P < 0.05).

Conclusion

In CKD, hepatic CSAD is depleted and taurine biosynthesis impaired. This is important in view of taurine’s reported protective effect against cardio-vascular disease - the leading cause of death in human CKD.
Six things to know about the homicides of doctors: a review of 30 years from Italy
Authors: Lorettu Liliana , Nivoli Alessandra M. A. , Daga Irma , Milia Paolo , Depalmas Cristiano , Nivoli Giancarlo , Bellizzi Saverio
Published: July 2021

Background

Healthcare workers have a 16 times greater risk of suffering workplace violence than workers in other sectors and around 50% experience workplace violence in the course of their career. The objective of this study is to explore the characteristics and circumstances of work-related killings of doctors.

Methods

Work-related homicides of doctors over the period 1988–2019 were identified retrospectively through the Italian national statistical agencies. Variables such as perpetrator, motive and location of the crime were obtained through forensic psychiatric work. After classification, the absolute and percent values of the main characteristics of the homicides were calculated.

Results

Over the period considered, 21 doctors were killed in Italy in connection with their professional activity. In 52% (n = 11) of cases, the killer was one of the doctor’s patients, in 29% (n = 6) of cases it was a patient’s relative, in 19% (n = 4) an occasional patient (first consultation). The location of the homicide was a community clinic in 48% (n = 10) of cases, the street in 19% (n = 4) of cases, the doctor’s home in 14% (n = 3), the hospital in 14% (n = 3) and the patient’s home in 5% (n = 1). In 57% (n = 12) of cases the perpetrator was not affected by any mental disorders. The motive for the homicide was revenge in 66.7% (n = 14) of cases; in 28.6% (n = 6) the revenge was preceded by stalking.

Conclusions

Doctors should be aware that the risk of being killed is not limited to hospital settings and that their patients’ family members might also pose a threat to them.
Comparison of dyad versus individual simulation-based training on stress, anxiety, cognitive load, and performance: a randomized controlled trial
Authors: Abbott Eduardo F. , Laack Torrey A. , Licatino Lauren K. , Wood-Wentz Christina M. , Warner Paul A. , Torsher Laurence C. , Newman James S. , Rieck Katie M.
Published: July 2021

Background

Dyad learning has been shown to be an effective tool for teaching procedural skills, but little is known about how dyad learning may impact the stress, anxiety, and cognitive load that a student experiences when learning in this manner. In this pilot study, we investigate the relationship between dyad training on stress, anxiety, cognitive load, and performance in a simulated bradycardia scenario.

Methods

Forty-one fourth-year medical school trainees were randomized as dyads (n = 24) or individuals (n = 17) for an education session on day 1. Reassessment occurred on day 4 and was completed as individuals for all trainees. Primary outcomes were cognitive load (Paas scale), stress (Cognitive Appraisal Ratio), and anxiety levels (abbreviated State-Trait Anxiety Inventory). Secondary outcomes were time-based performance metrics.

Results

On day 1 we observed significant differences for change in anxiety and stress measured before and after the training scenario between groups. Individuals compared to dyads had larger mean increases in anxiety, (19.6 versus 7.6 on 80-point scale, p = 0.02) and stress ratio (1.8 versus 0.9, p = 0.045). On the day 4 post-intervention assessment, no significant differences were observed between groups. Secondary outcomes were significant for shorter time to diagnosis of bradycardia (p = 0.01) and time to initiation of pacing (p = 0.04) in the dyad group on day 1. On day 4, only time to recognizing the indication for pacing was significantly shorter for individual training (hazard ratio [HR] = 2.26, p = 0.02).

Conclusions

Dyad training results in lower stress and anxiety levels with similar performance compared to individual training.
Identification of care tasks for the use of wearable transfer support robots – an observational study at nursing facilities using robots on a daily basis
Authors: Kato Kenji , Yoshimi Tatsuya , Tsuchimoto Shohei , Mizuguchi Nobuaki , Aimoto Keita , Itoh Naoki , Kondo Izumi
Published: July 2021

Background

To reduce the physical burden of caregivers, wearable transfer support robots are highly desirable. Although these robots are reportedly effective for specific tasks in experimental environments, there is little information about their effectiveness at nursing care facilities. The aim of this study was to identify care tasks and operations suitable for the use of these robots among caregivers in nursing facilities where these robots have been in use on a daily basis.

Methods

A 1-min observational time-motion analysis was conducted to examine care tasks and operations in two nursing facilities where wearable transfer support robots, namely Muscle Suit or HAL® Lumbar Type for Care Support, have been used routinely on a daily basis for more than 24 months.

Results

Analysis of the care tasks and their time ratio while wearing the equipment revealed that both robots were used conspicuously for direct care in over 70% of transits, especially during transfer assistance and toileting care. Furthermore, these robots were used intensively in the morning along with wake-up calls to care recipients, where pre-assigned wearers used them as part of their “routine work.”

Conclusions

We found that these wearable transfer support robots enabled effective performance of care tasks and operations in nursing facilities where these robots have been used on a daily basis for an extended period of time. These results may lead to the effective implementation and sustained operation of other types of care robots in the future.

Trial registration

UMIN Clinical Trials Registry no.UMIN000039204. Trial registration date: January 21, 2020. Interventional study. Parallel, non-randomized, single blinded.
Mitophagy in carcinogenesis, drug resistance and anticancer therapeutics
Authors: Guan Yanjie , Wang Yifei , Li Bo , Shen Kai , Li Quanfu , Ni Yingyin , Huang Lei
Published: July 2021

The mitochondrion is an organelle that plays a vital role in energy production, cytoplasmic protein degradation and cell death. Mitophagy is an autophagic procedure that specifically clears damaged mitochondria and maintains its homeostasis. Emerging evidence indicates that mitophagy is involved in many physiological processes, including cellular homeostasis, cellular differentiation and nerve protection. In this review, we describe the regulatory mechanisms of mitophagy in mammals and yeasts and highlight the recent advances relevant to its function in carcinogenesis and drug resistance. Finally, a section has been dedicated to describing the role of mitophagy in anticancer therapeutics, which is a new frontier that offers a precise and promising strategy.
Direct contact between Plasmodium falciparum and human B-cells in a novel co-culture increases parasite growth and affects B-cell growth
Authors: Reddy Sreenivasulu B. , Nagy Noemi , Rönnberg Caroline , Chiodi Francesca , Lugaajju Allan , Heuts Frank , Szekely Laszlo , Wahlgren Mats , Persson Kristina E. M.
Published: July 2021

Background

Plasmodium falciparumparasites cause malaria and co-exist in humans together with B-cells for long periods of time. Immunity is only achieved after repeated exposure. There has been a lack of methods to mimic the in vivo co-occurrence, where cells and parasites can be grown together for many days, and it has been difficult with long time in vitro studies.

Methods and results

A new method for growingP. falciparumin 5% CO2with a specially formulated culture medium is described. This knowledge was used to establish the co-culture of liveP. falciparumtogether with human B-cells in vitro for 10 days. The presence of B-cells clearly enhanced parasite growth, but less so when Transwell inserts were used (not allowing passage of cells or merozoites), showing that direct contact is advantageous. B-cells also proliferated more in presence of parasites. Symbiotic parasitic growth was verified using CESS cell-line and it showed similar results, indicating that B-cells are indeed the cells responsible for the effect. In malaria endemic areas, people often have increased levels of atypical memory B-cells in the blood, and in this assay it was demonstrated that when parasites were present there was an increase in the proportion of CD19 + CD20 + CD27 − FCRL4 + B-cells, and a contraction of classical memory B-cells. This effect was most clearly seen when direct contact between B-cells and parasites was allowed.

Conclusions

These results demonstrate thatP. falciparumand B-cells undoubtedly can affect each other when allowed to multiply together, which is valuable information for future vaccine studies.
Effect of statins on post-contrast acute kidney injury: a multicenter retrospective observational study
Authors: Lin Maoning , Xu Tian , Zhang Wenjuan , Li Duannbin , Li Ya , Hong Xulin , Luan Yi , Zhang Wenbin , Wang Min
Published: July 2021

Background

Post-contrast acute kidney injury (PC-AKI) is a severe complication of coronary angiography (CAG) and percutaneous coronary intervention (PCI). Currently, the effect of statins on PC-AKI and its mechanism remains unclear.

Methods

This multicenter retrospective observational study included 4386 patients who underwent CAG or PCI from December 2006 to December 2019 in Sir Run Run Shaw Hospital and its medical consortium hospitals. Serum creatinine pre- or post-procedure within 72 h after PCI was recorded. Multivariate logical regression was used to explore whether preoperative use of statins was protective from PC-AKI. The path analysis model was then utilized to look for the mediation factors of statins.

Results

Four thousand three hundred eighty-six patients were enrolled totally. The median age of the study population was 68 years old, 17.9% with PC-AKI, and 83.3% on preoperative statins therapy. The incidence of PC-AKI was significantly lower in group of patients on statins therapy. Multivariate regression indicated that preoperative statins therapy was significantly associated with lower percentage of elevated creatinine (β: -0.118,P < 0.001) and less PC-AKI (OR: 0.575,P < 0.001). In the preoperative statins therapy group, no statistically significant difference was detected between the atorvastatin and rosuvastatin groups (OR: 1.052,P = 0.558). Pathway model analysis indicated a direct protective effect of preoperative statins therapy on PC-AKI (P < 0.001), but not through its lipid-lowering effect (P = 0.277) nor anti-inflammatory effect (P = 0.596). Furthermore, it was found that “low-density lipoprotein cholesterol (LDL-C)→C-reactive protein (CRP)” mediated the relationship between preoperative statins therapy and PC-AKI (P = 0.007). However, this only explained less than 1% of the preoperative protective effects of statins on PC-AKI.

Conclusion

Preoperative statins therapy is an independent protective factor of PC-AKI, regardless of its type. This protective effect is not achieved by lipid-lowering effect or anti-inflammatory effect. These findings underscore the potential use of statins in preventing PC-AKI among those at risk.
Comparative colloidal stability, antitumor efficacy, and immunosuppressive effect of commercial paclitaxel nanoformulations
Authors: Ye Jun , Li Renjie , Yang Yanfang , Dong Wujun , Wang Yujie , Wang Hongliang , Sun Tong , Li Lin , Shen Qiqi , Qin Caiyun , Xu Xiaoyan , Liao Hengfeng , Jin Yiqun , Xia Xuejun , Liu Yuling
Published: July 2021

Background

Standard chemotherapy with taxanes, such as paclitaxel (PTX), remains the mainstay of systemic treatment of triple-negative breast cancer. Nanotechnology-based formulations have gradually replaced PTX injection and are widely used in China. However, no studies have compared the colloidal stability, antitumor efficacy, and safety of commercial PTX nanoformulations. Additionally, the desire to evaluate preclinical antitumor efficacy in human-derived tumor cells led to the widespread application of immunodeficient mouse models that likely contributed to the neglect of nanomedicines-immune system interactions. The present study investigated the colloidal stability, antitumor efficacy and safety, and nanomedicines-host immune system interactions of PTX nanoformulations. A further comparative analysis was performed to evaluate the clinical potential.

Results

Compared with liposome, PTX emulsion and PTX nanoparticle exhibited favorable colloidal stability. PTX emulsion was superior in inducing apoptosis and had a more pronounced inhibitory effect on 4T1-tumor spheroids compared with PTX liposome and PTX nanoparticle. Although PTX emulsion exhibited superior in vitro antitumor effect, no significant differences in the in vivo antitumor efficacy were found among the three types of PTX nanoformulations in an immunocompetent orthotopic 4T1 murine triple-negative breast cancer model. All PTX nanoformulations at maximum tolerated dose (MTD) induced lymphopenia and immunosuppression, as evidenced by the reduction of T cell subpopulations and inhibition of the dendritic cells maturation.

Conclusions

The MTD PTX nanomedicines-induced lymphopenia and immunosuppression may weaken the lymphocyte-mediated antitumor cellular immune response and partly account for the lack of differences in the in vivo antitumor outcomes of PTX nanoformulations. Understanding of what impacts PTX nanomedicines has on the immune system may be critical to improve the design and conduct of translational research of PTX nanomedicines in monotherapy or combination therapy with immunotherapy.

Graphic abstract
Same same-but different: using qualitative studies to inform concept elicitation for quality of life assessment in telemedical care: a request for an extended working model
Authors: Greffin Klara , Schmidt Silke , van den Berg Neeltje , Hoffmann Wolfgang , Ritter Oliver , Oeff Michael , Schomerus Georg , Muehlan Holger
Published: July 2021

Background

Although telemedical applications are increasingly used in the area of both mental and physical illness, there is no quality of life (QoL) instrument that takes into account the specific context of the healthcare setting. Therefore, the aim of this study was to determine a concept of quality of life in telemedical care to inform the development of a setting-sensitive patient-reported outcome measure.

Methods

Overall, 63 semi-structured single interviews and 15 focus groups with 68 participants have been conducted to determine the impact of telemedical care on QoL. Participants were patients with chronic physical or mental illnesses, with or without telemedicine supported healthcare as well as telemedical professionals. Mayring's content analysis approach was used to encode the qualitative data using MAXQDA software.

Results

The majority of aspects that influence the QoL of patients dealing with chronic conditions or mental illnesses could be assigned to an established working model of QoL. However, some aspects that were considered important (e. g. perceived safety) were not covered by the pre-existing domains. For that reason, we re-conceptualized the working model of QoL and added a sixth domain, referred to as healthcare-related domain.

Conclusion

Interviewing patients and healthcare professionals brought forth specific aspects of QoL evolving in telemedical contexts. These results reinforce the assumption that existing QoL measurements lack sensitivity to assess the intended outcomes of telemedical applications. We will address this deficiency by a telemedicine-related re-conceptualization of the assessment of QoL and the development of a suitable add-on instrument based on the resulting category system of this study.
HLA-dependent heterogeneity and macrophage immunoproteasome activation during lung COVID-19 disease
Authors: Desterke Christophe , Turhan Ali G. , Bennaceur-Griscelli Annelise , Griscelli Frank
Published: July 2021

Background

The worldwide pandemic caused by the SARS-CoV-2 virus is characterized by significant and unpredictable heterogeneity in symptoms that remains poorly understood.

Methods

Transcriptome and single cell transcriptome of COVID19 lung were integrated with deeplearning analysis of MHC class I immunopeptidome against SARS-COV2 proteome.

Results

An analysis of the transcriptomes of lung samples from COVID-19 patients revealed that activation of MHC class I antigen presentation in these tissues was correlated with the amount of SARS-CoV-2 RNA present. Similarly, a positive relationship was detected in these samples between the level of SARS-CoV-2 and the expression of a genomic cluster located in the 6p21.32 region (40 kb long, inside the MHC-II cluster) that encodes constituents of the immunoproteasome. An analysis of single-cell transcriptomes of bronchoalveolar cells highlighted the activation of the immunoproteasome in CD68 + M1 macrophages of COVID-19 patients in addition to a PSMB8-based trajectory in these cells that featured an activation of defense response during mild cases of the disease, and an impairment of alveolar clearance mechanisms during severe COVID-19. By examining the binding affinity of the SARS-CoV-2 immunopeptidome with the most common HLA-A, -B, and -C alleles worldwide, we found higher numbers of stronger presenters in type A alleles and in Asian populations, which could shed light on why this disease is now less widespread in this part of the world.

Conclusions

HLA-dependent heterogeneity in macrophage immunoproteasome activation during lung COVID-19 disease could have implications for efforts to predict the response to HLA-dependent SARS-CoV-2 vaccines in the global population.
Multicenter randomized controlled trial comparing digital and traditional chest drain in a VATS pulmonary lobectomy cohort: interim analysis
Authors: Mendogni Paolo , Tosi Davide , Marulli Giuseppe , Comacchio Giovanni Maria , Pieropan Sara , Rossi Veronica , Brascia Debora , Andriolo Luigi Gaetano , Imbriglio Giovanna , Bonitta Gianluca , Lopez Camillo , Rea Federico , Nosotti Mario
Published: July 2021

Background

The usefulness of digital chest drain is still debated. We are carrying out a study to determine if the use of a digital system compared with a traditional system reduces the duration of chest drainage. To evaluate safety, benefit, or futility of this trial we planned the current interim analysis.

Methods

An interim analysis on preliminary data from ongoing investigator-initiated, multicenter, interventional, prospective randomized trial. Original protocol number: (NCT03536130). The interim main endpoint was overall complications; secondary endpoints were the concordance between the two primary endpoints of the RCT (chest tube duration and length of hospital stay). We planned the interim analysis when half of the patients have been randomised and completed the study. Data were described using mean and standard deviation or absolute frequencies and percentage. T-test for unpaired samples, Chi-square test, Poisson regression and absolute standardized mean difference (ASMD) were used. P-value < 0.05 was considered significant.

Results

From April 2017 to November 2018, out of 317 patients enrolled by 3 centers, 231 fulfilled inclusion criteria and were randomized. Twenty-two of them dropped out after randomization. Finally, 209 patients were analyzed: among them 94 used the digital device and 115 the traditional one. The overall postoperative complications were 35 (16.8%) including prolonged air leak (1.9%). Mean chest tube duration was 3.6 days (SD = 1.8), with no differences between two groups (p = 0.203). The overall difference between hospital stay and chest tube duration was 1.4 days (SD = 1.4). Air leak at first postoperative day detected by digital and traditional devices predicted increasing in tube duration of 1.6 day (CI 95% 0.8–2.5, p < 0.001) and 2.0 days (CI 95% 1.0–3.1, p < 0.001), respectively.

Conclusions

This interim analysis supported the authors’ will to continue with the enrollment and to analyze data once the estimated sample size will be reached.

Trial registration

Trial registration number NCT03536130, Registered 24 May 2018 - Retrospectively registered.
Plant super-barcode: a case study on genome-based identification for closely related species of Fritillaria
Authors: Wu Lan , Wu Mingli , Cui Ning , Xiang Li , Li Ying , Li Xiwen , Chen Shilin
Published: July 2021

Background

Although molecular analysis offers a wide range of options for species identification, a universal methodology for classifying and distinguishing closely related species remains elusive. This study validated the effectiveness of utilizing the entire chloroplast (cp) genome as a super-barcode to help identify and classify closely related species.

Methods

We here compared 26 complete cp genomes of ten Fritillaria species including 18 new sequences sequenced in this study. Each species had repeats and the cp genomes were used as a whole DNA barcode to test whether they can distinguish Fritillaria species.

Results

The cp genomes of Fritillaria medicinal plants were conserved in genome structure, gene type, and gene content. Comparison analysis of the Fritillaria cp genomes revealed that the intergenic spacer regions were highly divergent compared with other regions. By constructing the phylogenetic tree by the maximum likelihood and maximum parsimony methods, we found that the entire cp genome showed a high discrimination power for Fritillaria species with individuals of each species in a monophyletic clade. These results indicate that cp genome can be used to effectively differentiate medicinal plants from the genus Fritillaria at the species level.

Conclusions

This study implies that cp genome can provide distinguishing differences to help identify closely related Fritillaria species, and has the potential to be served as a universal super-barcode for plant identification.
Nuclear Transglutaminase 2 interacts with topoisomerase II⍺ to promote DNA damage repair in lung cancer cells
Authors: Lei Xiao , Cao Kun , Chen Yuanyuan , Shen Hui , Liu Zhe , Qin Hongran , Cai Jianming , Gao Fu , Yang Yanyong
Published: July 2021

Background

To block repairs of DNA damages, especially the DNA double strand break (DSB) repair, can be used to induce cancer cell death. DSB repair depends on a sequential activation of DNA repair factors that may be potentially targeted for clinical cancer therapy. Up to now, many protein components of DSB repair complex remain unclear or poorly characterized. In this study, we discovered that Transglutaminase 2 (TG2) acted as a new component of DSB repair complex.

Methods

A bioinformatic analysis was performed to identify DNA damage relative genes from dataset from The Cancer Genome Atlas. Immunofluorescence and confocal microscopy were used to monitor the protein localization and recruitment kinetics. Furthermore, immunoprecipitation and mass spectrometry analysis were performed to determine protein interaction of both full-length and fragments or mutants in distinct domain. In situ lung cancer model was used to study the effects cancer therapy in vivo.

Results

After DSB induction, cytoplasmic TG2 was extensively mobilized and translocated into nucleus after phosphorylated at T162 site by DNA-PKcs. Nuclear TG2 quickly accumulated at DSB sites and directly interacting with Topoisomerase IIα (TOPOIIα) with its TGase domain to promote DSB repair. TG2 deficient cells lost capacity of DSB repair and become susceptible to ionizing radiation. Specific inhibition of TG2-TOPOIIα interaction by glucosamine also significantly inhibited DSB repair, which increased sensitivity in lung cancer cells and engrafted lung cancers.

Conclusions

These findings elucidate new mechanism of TG2 in DSB repair trough directly interacting with TOPOIIα, inhibition of which provided potential target for overcoming cancer resistance.