bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractBackgroundMales 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.MethodsWe 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.ResultsWe 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.ConclusionsMales 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

Abstract
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

Abstract
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

Abstract
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

AbstractBackgroundTo 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.MethodsA 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.ResultsAnalysis 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.”ConclusionsWe 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 registrationUMIN 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

AbstractThe 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

AbstractBackgroundPlasmodium 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 resultsA 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.ConclusionsThese 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

AbstractBackgroundPost-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.MethodsThis 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.ResultsFour 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.ConclusionPreoperative 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

Abstract
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

Abstract
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

Abstract
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.