bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular and cellular features of CTLA-4 blockade for relapsed myeloid malignancies after transplantation
Authors: Penter Livius , Zhang Yi , Savell Alexandra , Huang Teddy , Cieri Nicoletta , Thrash Emily M. , Kim-Schulze Seunghee , Jhaveri Aashna , Fu Jingxin , Ranasinghe Srinika , Li Shuqiang , Zhang Wandi , Hathaway Emma S. , Nazzaro Matthew , Kim Haesook T. , Chen Helen , Thurin Magdalena , Rodig Scott J. , Severgnini Mariano , Cibulskis Carrie , Gabriel Stacey , Livak Kenneth J. , Cutler Corey , Antin Joseph H. , Nikiforow Sarah , Koreth John , Ho Vincent T. , Armand Philippe , Ritz Jerome , Streicher Howard , Neuberg Donna , Hodi F. Stephen , Gnjatic Sacha , Soiffer Robert J. , Liu X. Shirley , Davids Matthew S. , Bachireddy Pavan , Wu Catherine J.
Published: March 2021

Relapsed myeloid disease after allogeneic stem cell transplantation (HSCT) remains largely incurable. We previously demonstrated the potent activity of immune checkpoint blockade in this clinical setting with ipilimumab or nivolumab. To define the molecular and cellular pathways by which CTLA-4 blockade with ipilimumab can reinvigorate an effective graft-versus-leukemia (GVL) response, we integrated transcriptomic analysis of leukemic biopsies with immunophenotypic profiling of matched peripheral blood samples collected from patients treated with ipilimumab following HSCT on the Experimental Therapeutics Clinical Trials Network 9204 trial. Response to ipilimumab was associated with transcriptomic evidence of increased local CD8+ T-cell infiltration and activation. Systemically, ipilimumab decreased naïve and increased memory T-cell populations and increased expression of markers of T-cell activation and costimulation such as PD-1, HLA-DR, and ICOS, irrespective of response. However, responding patients were characterized by higher turnover of T-cell receptor sequences in peripheral blood and showed increased expression of proinflammatory chemokines in plasma that was further amplified by ipilimumab. Altogether, these data highlight the compositional T-cell shifts and inflammatory pathways induced by ipilimumab both locally and systemically that associate with successful GVL outcomes. This trial was registered at www.clinicaltrials.gov as #NCT01822509.
Mitochondrial dynamics and reactive oxygen species initiate thrombopoiesis from mature megakaryocytes
Authors: Poirault-Chassac Sonia , Nivet-Antoine Valérie , Houvert Amandine , Kauskot Alexandre , Lauret Evelyne , Lai-Kuen René , Dusanter-Fourt Isabelle , Baruch Dominique
Published: March 2021

Blood platelets are essential for controlling hemostasis. They are released by megakaryocytes (MKs) located in the bone marrow, upon extension of cytoplasmic protrusions into the lumen of bone marrow sinusoids. Their number increases in postpulmonary capillaries, suggesting a role for oxygen gradient in thrombopoiesis (ie, platelet biogenesis). In this study, we show that initiation of thrombopoiesis from human mature MKs was enhanced under hyperoxia or during pro-oxidant treatments, whereas antioxidants dampened it. Quenching mitochondrial reactive oxygen species (mtROS) with MitoTEMPO decreased thrombopoiesis, whereas genetically enhancing mtROS by deacetylation-null sirtuin-3 expression increased it. Blocking cytosolic ROS production by NOX inhibitors had no impact. Classification according to the cell roundness index delineated 3 stages of thrombopoiesis in mature MKs. Early-stage round MKs exhibited the highest index, which correlated with low mtROS levels, a mitochondrial tubular network, and the mitochondrial recruitment of the fission activator Drp1. Intermediate MKs at the onset of thrombopoiesis showed high mtROS levels and small, well-delineated mitochondria. Terminal MKs showed the lowest roundness index and long proplatelet extensions. Inhibiting Drp1-dependent mitochondrial fission of mature MKs by Mdivi-1 favored a tubular mitochondrial network and lowered both mtROS levels and intermediate MKs proportion, whereas enhancing Drp1 activity genetically had opposite effects. Reciprocally, quenching mtROS limited mitochondrial fission in round MKs. These data demonstrate a functional coupling between ROS and mitochondrial fission in MKs, which is crucial for the onset of thrombopoiesis. They provide new molecular cues that control initiation of platelet biogenesis and may help elucidate some unexplained thrombocytopenia.
A change in temporal muscle thickness is correlated with past energy adequacy in bedridden older adults: a prospective cohort study
Authors: Hasegawa Yoko , Yoshida Mikako , Sato Aya , Fujimoto Yumiko , Minematsu Takeo , Sugama Junko , Sanada Hiromi
Published: March 2021

Background

Energy inadequacy has a great impact on health outcomes in older adult patients; however, it is difficult to evaluate energy adequacy in these patients, especially in home-care settings. We recently reported that temporal muscle thickness can be an indicator of nutritional status. The present study aims to examine whether a change in temporal muscle thickness is directly correlated with energy adequacy and, if so, to determine the cutoff value of a change in temporal muscle thickness to detect energy inadequacy.

Methods

A prospective cohort study was conducted from September 2015 to June 2016 in two hospitals in Japan, and included bedridden older adult patients aged ≥65 years. Temporal muscle thickness was measured using ultrasonography. Energy intake was estimated by photographic diet records. Total energy expenditure (TEE) was estimated by multiplying basal energy expenditure calculated using the Harris– Benedict equation by activity and stress factors. Energy adequacy was then calculated by dividing TEE by energy intake. Pearson’s correlation coefficient was used to examine the relationship between percentage change in temporal muscle thickness and energy adequacy. Multiple logistic regression analysis was conducted to determine the direct relationship between percentage change in temporal muscle thickness and moderate energy inadequacy (energy adequacy< 75%). Receiver operating characteristic (ROC) analysis was performed to determine the cutoff point for percentage change in temporal muscle thickness to detect moderate energy inadequacy.

Results

Forty-eight patients were analyzed (mean age 84.4 ± 7.8 years; 54.2% were women). The percentage change in muscle thickness was significantly correlated with energy adequacy (r = 0.733, p < 0.001). ROC analysis identified a percentage change in temporal muscle thickness of − 3.6% as the optimal cutoff point for detecting moderate energy inadequacy. Percentage change in muscle thickness was independently correlated with energy inadequacy after adjusting for age, sex, and masticatory status (AOR 0.281, 95% CI 0.125–0.635).

Conclusions

Changes in temporal muscle thickness are directly correlated with energy adequacy and can indicate moderate energy inadequacy in bedridden older adults. These results suggest the assessment of changes in temporal muscle thickness could be useful for guiding nutritional care in older adult patients in home-care settings.
Correction to: Changes in hemodialysis catheter management after introduction of the end-stage renal disease prospective payment system
Authors: Roetker Nicholas S. , Guo Haifeng , Decker-Palmer Marquita R. , Peng Yi , Wetmore James B.
Published: March 2021

An amendment to this paper has been published and can be accessed via the original article.
Pregnancy-related anxiety and its associated factors during COVID-19 pandemic in Iranian pregnant women: a web-based cross-sectional study
Authors: Hamzehgardeshi Zeinab , Omidvar Shabnam , Amoli Arman Asadi , Firouzbakht Mojgan
Published: March 2021

Background

Pregnancy is a risk factor for coronavirus disease 2019 (COVID-19). Pregnant women suffer from varying levels of pregnancy-related anxiety (PRA) which can negatively affect pregnancy outcomes. The aim of this study was to assess PRA and its associated factors during the COVID-19 pandemic.

Methods

This web-based cross-sectional study was conducted in 2020 on 318 pregnant women purposively recruited from primary healthcare centers in Sari and Amol, Iran. Data were collected using questionnaires (PRAQ, Edinburg, KAP of COVID-19, CDA-Q and Demographic questionnaire), which were provided to participants through the social media or were completed for them over telephone. Data were analyzed with the linear regression and the logistic regression analysis, at the significance level of 0.05 using the SPSS software (v. 21).

Results

Around 21% of participants had PRA, 42.1% had depression, and 4.4% had COVID-19 anxiety. The significant predictors of PRA were number of pregnancies (P = 0.008), practice regarding COVID-19 (P < 0.001), COVID-19 anxiety (P < 0.001), depression (P < 0.001), and social support (P = 0.025) which explained 19% of the total variance. Depression and COVID-19 anxiety increased the odds of PRA by respectively four times and 13%, while good practice regarding COVID-19 decreased the odds by 62%.

Conclusion

Around 21% of pregnant women suffer from PRA during the COVID-19 pandemic and the significant predictors of PRA during the pandemic include number of pregnancies, practice regarding COVID-19, COVID-19 anxiety, depression, and social support. These findings can be used to develop appropriate strategies for the management of mental health problems during pregnancy in the COVID-19 pandemic.
The characteristics of circRNA as competing endogenous RNA in pathogenesis of acute myeloid leukemia
Authors: Zhang Siyuan
Published: March 2021

Background

As one of the novel molecules, circRNA has been identified closely involved in the pathogenesis of many diseases. However, the function of circRNA in acute myeloid leukemia (AML) still remains unknown.

Methods

In the current study, the RNA expression profiles were obtained from Gene Expression Omnibus (GEO) datasets. The differentially expressed RNAs were identified using R software and the competing endogenous RNA (ceRNA) network was constructed using Cytoscape. Functional and pathway enrichment analyses were performed to identify the candidate circRNA-mediated aberrant signaling pathways. The hub genes were identified by MCODE and CytoHubba plugins of Cytoscape, and then a subnetwork regulatory module was established.

Results

A total of 27 circRNA-miRNA pairs and 208 miRNA-mRNA pairs, including 12 circRNAs, 24 miRNAs and 112 mRNAs were included in the ceRNA network. Subsequently, a subnetwork, including 4 circRNAs, 5 miRNAs and 6 mRNAs, was established based on related circRNA-miRNA-mRNA regulatory modules.

Conclusions

In summary, this work analyzes the characteristics of circRNA as competing endogenous RNA in AML pathogenesis, which would provide hints for developing novel prognostic, diagnostic and therapeutic strategy for AML.
A place-based analysis of COVID-19 risk factors in Bangladesh urban slums: a secondary analysis of World Bank microdata
Authors: Hasan Shaikh Mehdi , Das Susmita , Hanifi Syed Manzoor Ahmed , Shafique Sohana , Rasheed Sabrina , Reidpath Daniel D.
Published: March 2021

Background

There is a lack of research investigating the confluence of risk factors in urban slums that may make them accelerators for respiratory, droplet infections like COVID-19. Our working hypothesis was that, even within slums, an inverse relationship existed between living density and access to shared or private WASH facilities.

Methods

In an exploratory, secondary analysis of World Bank, cross-sectional microdata from slums in Bangladesh we investigated the relationship between intra-household population density (crowding) and access to private or shared water sources and toilet facilities.

Results

The analysis showed that most households were single-room dwellings (80.4%). Median crowding ranged from 0.55 m2per person up to 67.7 m2per person. The majority of the dwellings (83.3%), shared both toilet facilities and the source of water, and there was a significant positive relationship between crowding and the use of shared facilities.

Conclusion

The findings highlight the practical constraints on implementing, in slums, the conventional COVID19 management approaches of social distancing, regular hand washing, and not sharing spaces. It has implications for the management of future respiratory epidemics.
NO2 exposure increases eczema outpatient visits in Guangzhou, China: an indication for hospital management
Authors: Zhang Luwen , Jing Dian , Lu Qiaochu , Shen Shuqun
Published: March 2021

Background

Ambient nitrogen dioxide (NO2) is a common air pollutant in developing countries and causes skin conditions, but its effect on eczema in subtropical areas is not clear in China.

Object

To measure the effect of short-term exposure of NO2 on the incidence of eczema and the change of outpatient visits.

Methods

Data of daily temperature, air pollutants, and outpatient visits from 2013 to 2018 were collected in a row. The generalized additive model (GAM) and Poisson distribution were used to assess the association between short-term exposure of NO2 and the outpatient visits of patients with eczema. The cumulative exposure effect of lag 0–3 days and the displacement effect of NO2 and other pollutants were considered as well. A single pollutant model was used to examine the independent association, and a two-pollutant model was adopted to control the confounding effect.

Results

The daily outpatient visits of eczema increased from 75.26 to 190.85 from 2013 to 2018 (P < 0.001). The combined influence of NO2 and the related pollutant exerted a stronger influence on the incidence of eczema. The maximum effect of NO2 appeared on the exposed day.

(lag 0) and disappeared on day 4 (lag 3). The children and seniors were more vulnerable to NO2 exposure.

Conclusion

Exposure to NO2 is tightly associated with eczema incidence and outpatient visits. The hospitals should react to the visit fluctuations and adjust physician duty shifts to improve outpatient service efficiency.
Association between plasma interleukin-33 level and acute exacerbation of chronic obstructive pulmonary disease
Authors: Joo Hyonsoo , Park Seoung Ju , Min Kyung Hoon , Rhee Chin Kook
Published: March 2021

Background

The role of interleukin (IL)-33 in patients with chronic obstructive pulmonary disease (COPD) has not been well elucidated. The aim of this study is to analyze the association between plasma IL-33 level and acute exacerbation of COPD.

Methods

Plasma IL-33 was measured in 62 COPD patients during their stable state. Patients were prospectively followed up for 1 year. The expression of IL-33 was measured in lung tissue obtained from 38 patients who underwent surgery.

Results

The number of exacerbations was significantly higher in the high plasma IL-33 group compared with the low plasma IL-33 group. On Poisson regression analysis, high plasma IL-33 was associated with increased risk of exacerbation (incidence rate ratio = 2.166, P = 0.043). The expression of IL-33 in the lung was higher in COPD patients than in controls. The expression of IL-33 was significantly correlated with smoking pack years (R = 0.45, P < 0.01) and Forced expiratory volume in 1 s (%) (R = − 0.58, P < 0.01).

Conclusion

The plasma level of IL-33 in patients with COPD was significantly associated with the risk of exacerbation in prospective follow up. The expression of IL-33 in the lung was positively correlated with smoking and negatively correlated with lung function.
Muscle volume imbalance may be associated with static posterior humeral head subluxation
Authors: Mitterer Marian , Matis Nicholas , Steiner Gernot , Vasvary Imre , Ortmaier Reinhold
Published: March 2021

Background

The transverse force couple (TFC) of the rotator cuff (subscapularis vs. infraspinatus and teres minor muscle) is an important dynamic stabilizer of the shoulder joint in the anterior-posterior direction. In patients with posterior static subluxation of the humeral head (PSSH), decentration of the humeral head posteriorly occurs, which is associated with premature arthritis. We hypothesize that not only pathologic glenoid retroversion but also chronic muscle volume imbalance in the transverse force couple leads to PSSH.

Methods

A retrospective analysis of the TFC muscle volumes of 9 patients with symptomatic, atraumatic PSSH, within 8 were treated with glenoid correction osteotomy, was conducted. The imaging data (CT) of 9 patients/10 shoulders of the full scapula and shoulder were analyzed, and the muscle volumes of the subscapularis (SSC), infraspinatus (ISP) and teres minor muscles (TMM) were measured by manually marking the muscle contours on transverse slices and calculating the volume from software. Furthermore, the glenoid retroversion and glenohumeral distance were measured.

Results

The mean glenoid retroversion was − 16° (− 7° to − 31°). The observed mean glenohumeral distance was 4.0 mm (0 to 6.8 mm). Our study population showed a significant muscle volume imbalance between the subscapularis muscle and the infraspinatus and teres minor muscles (192 vs. 170 ml; p = 0.005). There was no significant correlation between the subscapularis muscle volume and the glenohumeral distance (r = 0.068), (p = 0.872).

Conclusion

The muscle volume of the SSC in patients with PSSH was significantly higher than the muscle volume of the posterior force couple (ISP and TMM). This novel finding, albeit in a small series of patients, may support the theory that transverse force couple imbalance is associated with PSSH.

Level of evidence

Level 4 – Case series with no comparison group.
Evaluation of metabolic equivalents of task (METs) in the preoperative assessment in aortic repair
Authors: Zientara Alicja , Schwegler Igor , Dzemali Omer , Bruijnen Hans , Bernheim Alain , Dick Florian , Attigah Nicolas
Published: March 2021

Background

Reliable prediction of the preoperative risk is of crucial importance for patients undergoing aortic repair. In this retrospective cohort study, we evaluated the metabolic equivalent of task (MET) in the preoperative risk assessment with clinical outcome in a cohort of consecutive patients.

Methods

Retrospective analysis of prospectively collected data in a single center unit of 296 patients undergoing open or endovascular aortic repair from 2009 to 2016. The patients were divided into four anatomic main groups (infrarenal (endo: n = 94; open: n = 88), juxta- and para-renal (open n = 84), thoraco-abdominal (open n = 13) and thoracic (endo: n = 11; open: n = 6). Out of these, 276 patients had a preoperative statement of their functional capacity in metabolic units and were evaluated concerning their postoperative outcome including survival, in-hospital mortality, postoperative complications, myocardial infarction and stroke, and the need of later cardiovascular interventions.

Results

The median follow-up of the cohort was 10.8 months. Patients with < 4MET had a higher incidence of diabetes mellitus (p = 0.0002), peripheral arterial disease (p < 0.0001), history of smoking (p = 0.003), obesity (p = 0.03) and chronic obstructive pulmonary disease (p = 0.05). Overall in-hospital mortality was 4.4% (13 patients). There was no significant difference in the survival between patients with a functional capacity of more than 4 MET (220 patients, mean survival: 74.5 months) and patients with less than 4 MET (56 patients, mean survival: 65.4 months) (p = 0.64). The mean survival of the infrarenal cohort (n = 169) was 74.3 months with no significant differences between both MET groups (> 4 MET: 131 patients, mean survival 75.5 months; < 4 MET: 38 patients, mean survival 63.6 months. p = 0.35). The subgroup after open surgical technique with less than 4 MET had the lowest mean survival of 38.8 months. In 46 patients with > 4MET (20.9%) perioperative complications occurred compared to the group with < 4MET with 18 patients (32.1%) (p = 0.075). There were no significant differences in both groups in the late cardiovascular interventions (p = 0.91) and major events including stroke and myocardial infarction (p = 0.4) monitored during the follow up period. The risk to miss a potential need for cardiac optimization in patients > 4MET was 7%.

Conclusion

The functional preoperative evaluation by MET in patients undergoing aortic surgery is a useful surrogate marker of perioperative performance but cannot be seen as a substitute for preoperative cardiopulmonary testing in selected individuals. Trial registration clinicaltrials.gov, registration number NCT03617601 (retrospectively registered).
Genome-scale model reconstruction of the methylotrophic yeast Ogataea polymorpha
Authors: Liebal Ulf W , Fabry Brigida A , Ravikrishnan Aarthi , Schedel Constantin VL , Schmitz Simone , Blank Lars M , Ebert Birgitta E
Published: March 2021

Background

Ogataea polymorpha is a thermotolerant, methylotrophic yeast with significant industrial applications. While previously mainly used for protein synthesis, it also holds promise for producing platform chemicals. O. polymorpha has the distinct advantage of using methanol as a substrate, which could be potentially derived from carbon capture and utilization streams. Full development of the organism into a production strain and estimation of the metabolic capabilities require additional strain design, guided by metabolic modeling with a genome-scale metabolic model. However, to date, no genome-scale metabolic model is available for O. polymorpha.

Results

To overcome this limitation, we used a published reconstruction of the closely related yeast Komagataella phaffii as a reference and corrected reactions based on KEGG and MGOB annotation. Additionally, we conducted phenotype microarray experiments to test the suitability of 190 substrates as carbon sources. Over three-quarter of the substrate use was correctly reproduced by the model and 27 new substrates were added, that were not present in the K. phaffii reference model.

Conclusion

The developed genome-scale metabolic model of O. polymorpha will support the engineering of synthetic metabolic capabilities and enable the optimization of production processes, thereby supporting a sustainable future methanol economy.
Optimising student-led interprofessional learning across eleven health disciplines
Authors: van Diggele Christie , Roberts Chris , Haq Inam
Published: March 2021

Background

Provision of effective Interprofessional learning (IPL) opportunities plays a vital role in preparing healthcare students for future collaborative practice. There is an identified need for universities to better prepare students for interprofessional teamwork, however, few large-scale IPL activities have been reported. Additionally, little has been reported on disciplinary differences in student learning experience. The Health Collaboration Challenge (HCC) is a large-scale IPL activity held annually at the University of Sydney. This study sought to explore students’ experience of early participation in an interprofessional case-based learning activity, and the similarities and differences in the perceived value of interprofessional (social) learning for each discipline.

Methods

In 2018, 1674 students from 11 disciplines (dentistry, oral health, nursing, pharmacy, medicine, occupational therapy, speech pathology, physiotherapy, dietetics, diagnostic radiography, exercise physiology) participated in the HCC. Students worked in teams to produce a video and patient management plan based on a patient case. Participants completed a questionnaire, including closed and open-ended items. Quantitative data were analysed using descriptive statistics. Thematic analysis was used to code and categorise qualitative data into themes. These themes were then applied and quantified at a disciplinary level to measure prevalence.

Results

In total, 584/1674 (35%) of participants responded to the questionnaire. Overall, students perceived their experience to be largely beneficial to their learning and interprofessional skill development. Positive aspects included opportunities for peer learning, collaboration, networking, and understanding the different roles and responsibilities of other health professions. Negative aspects included the video form of assessment, inequity in assessment weighting across disciplines, the discipline mix within teams and lack of case relevance.

Conclusion

The learning activity provided a framework for students to practice and develop their skills in interprofessional teamwork, as they prepare for increased clinical placements. Overall, students perceived their experience as beneficial to their learning and professional development early in their degree. However, they expressed dissatisfaction with the inequity of assessment weighting across the disciplines; lack of relevance of the case across disciplines; and the activity of producing a video. Further research is needed regarding the ideal number of disciplines to include in teamwork specific to a patient case.
Gut microbiota-mediated lysophosphatidylcholine generation promotes colitis in intestinal epithelium-specific Fut2 deficiency
Authors: Tang Xuelian , Wang Weijun , Hong Gaichao , Duan Caihan , Zhu Siran , Tian Yuen , Han Chaoqun , Qian Wei , Lin Rong , Hou Xiaohua
Published: March 2021

Background and aims

Previous study disclosed Fucosyltransferase 2 (Fut2) gene as a IBD risk locus. This study aimed to explore the mechanism of Fut2 in IBD susceptibility and to propose a new strategy for the treatment of IBD.

Methods

Intestinal epithelium-specific Fut2 knockout (Fut2△IEC) mice was used. Colitis was induced by dextran sulfate sodium (DSS). The composition and diversity of gut microbiota were assessed via 16S rRNA analysis and the metabolomic findings was obtained from mice feces via metabolite profiling. The fecal microbiota transplantation (FMT) experiment was performed to confirm the association of gut microbiota and LPC. WT mice were treated with Lysophosphatidylcholine (LPC) to verify its impact on colitis.

Results

The expression of Fut2 and α-1,2-fucosylation in colonic tissues were decreased in patients with UC (UC vs. control, P = 0.036) and CD (CD vs. control, P = 0.031). When treated with DSS, in comparison to WT mice, more severe intestinal inflammation and destructive barrier functions in Fut2△IEC mice was noted. Lower gut microbiota diversity was observed in Fut2△IEC mice compared with WT mice (p < 0.001). When exposed to DSS, gut bacterial diversity and composition altered obviously in Fut2△IEC mice and the fecal concentration of LPC was increased. FMT experiment revealed that mice received the fecal microbiota from Fut2△IEC mice exhibited more severe colitis and higher fecal LPC concentration. Correlation analysis showed that the concentration of LPC was positively correlated with four bacteria—Escherichia, Bilophila, Enterorhabdus and Gordonibacter. Furthermore, LPC was proved to promote the release of pro-inflammatory cytokines and damage epithelial barrier in vitro and in vivo.

Conclusion

Fut2 and α-1,2-fucosylation in colon were decreased not only in CD but also in UC patients. Gut microbiota in Fut2△IEC mice is altered structurally and functionally, promoting generation of LPC which was proved to promote inflammation and damage epithelial barrier.
The inhibitory effect of melatonin on human prostate cancer
Authors: Shen Dexin , Ju Lingao , Zhou Fenfang , Yu Mengxue , Ma Haoli , Zhang Yi , Liu Tongzu , Xiao Yu , Wang Xinghuan , Qian Kaiyu
Published: March 2021

Prostate cancer (PCa) is one of the most commonly diagnosed human cancers in males. Nearly 191,930 new cases and 33,330 new deaths of PCa are estimated in 2020. Androgen and androgen receptor pathways played essential roles in the pathogenesis of PCa. Androgen depletion therapy is the most used therapies for primary PCa patients. However, due to the high relapse and mortality of PCa, developing novel noninvasive therapies have become the focus of research. Melatonin is an indole-like neurohormone mainly produced in the human pineal gland with a prominent anti-oxidant property. The anti-tumor ability of melatonin has been substantially confirmed and several related articles have also reported the inhibitory effect of melatonin on PCa, while reviews of this inhibitory effect of melatonin on PCa in recent 10 years are absent. Therefore, we systematically discuss the relationship between melatonin disruption and the risk of PCa, the mechanism of how melatonin inhibited PCa, and the synergistic benefits of melatonin and other drugs to summarize current understandings about the function of melatonin in suppressing human prostate cancer. We also raise several unsolved issues that need to be resolved to translate currently non-clinical trials of melatonin for clinic use. We hope this literature review could provide a solid theoretical basis for the future utilization of melatonin in preventing, diagnosing and treating human prostate cancer.
Correction to: COVID-19 biomarkers for severity mapped to polycystic ovary syndrome
Authors: Moin Abu Saleh Md , Sathyapalan Thozhukat , Atkin Stephen L. , Butler Alexandra E.
Published: March 2021

An amendment to this paper has been published and can be accessed via the original article.
Different needs in patients with schizophrenia spectrum disorders who behave aggressively towards others depend on gender: a latent class analysis approach
Authors: Günther Moritz Philipp , Lau Steffen , Kling Sabine , Sonnweber Martina , Habermeyer Elmar , Kirchebner Johannes
Published: March 2021

Background

There is limited research with inconsistent findings on differences between female and male offender patients with a schizophrenia spectrum disorder (SSD), who behave aggressively towards others. This study aimed to analyse inhomogeneities in the dataset and to explore, if gender can account for those.

Methods

Latent class analysis was used to analyse a mixed forensic dataset consisting of 31 female and 329 male offender patients with SSD, who were accused or convicted of a criminal offence and were admitted to forensic psychiatric inpatient treatment between 1982 and 2016 in Switzerland.

Results

Two homogenous subgroups were identified among SSD symptoms and offence characteristics in forensic SSD patients that can be attributed to gender. Despite an overall less severe criminal and medical history, the female-dominated class was more likely to receive longer prison terms, similarly high antipsychotic dosages, and was less likely to benefit from inpatient treatment. Earlier findings were confirmed and extended in terms of socio-demographic variables, diseases and criminal history, comorbidities (including substance use), the types of offences committed in the past and as index offence, accountability assumed in court, punishment adjudicated, antipsychotic treatment received, and the development of symptoms during psychiatric inpatient treatment.

Conclusions

Female offender patients with schizophrenia might need a more tailored approach in prevention, assessment and treatment to diminish tendencies of inequity shown in this study.
Finite element analysis of different locking plate fixation methods for the treatment of ulnar head fracture
Authors: Zhang Yue , Shao Qin , Yang Chensong , Ai Changqing , Zhou Di , Yu Yang , Sun Guixin
Published: March 2021

Background

Ulnar head fractures are increasingly higher with the growing proportion of the elderly people. Failure to achieve a stable anatomic reduction of ulna head fracture may lead to a distal radioulnar joint (DRUJ) dysfunction and nonunion of the distal radius. Due to the lack of the postoperative reporting outcomes and the biomechanical studies, it has not been well established about the optimal management of the comminuted distal ulna head fracture. Hence, the purpose of this study is to use finite element analysis to explain the advantages and disadvantages of ulnar-side locking plate fixation compared with dorsal-side locking plate fixation and its screw arrangement in the treatment of ulnar head fractures.

Methods

FE models of the ulnar head fracture and the models of ulnar-side locking plate and dorsal-side plate with two or three distal screws was constructed. In order to simulate forces acting on the ulnar and the osteosynthesis material during daily-life activity in subjects who underwent reconstructive surgery, we applied three loading conditions to each model, viz. 20 N axial compression, 50 N axial compression, 1 N∙m torsion moment, 1 N∙m lateral bending moments, and 1 N∙m extension bending moments. Under these conditions, values of the von Mises stress (VMS) distribution of the implant, peak VMS, the relative displacement of the head and shaft fragments between the fracture ends and the displacement and its direction of the models were investigated.

Results

The stress values of ulnar-side plates were lower than those of dorsal-side plates. And the ulnar-plate fixation system also has smaller maximum displacement and relative displacement. When adding a screw in the middle hole of the ulnar head, the values of model displacement and the peak stress in fixation system are lower, but it may evidently concentrate the stress on the middle screw.

Conclusions

In conclusion, our study indicated that ulnar-side locking plates resulted in a lower stress distribution in the plate and better stability than dorsal-side locking plates for ulnar head fracture fixation. Adding an additional screw to the ulnar head could increase the stability of the fixation system and provide an anti-torsion function. This study requires clinical confirmation of its practicality in the treatment of ulnar head fractures. This study requires clinical confirmation as to its practicality in the treatment of ulnar head fracture.
Characteristics of three-dimensional acetabular morphology of patients with excellent outcome after rotational acetabular osteotomy over 20 years
Authors: Tanaka Takeyuki , Moro Toru , Ishikura Hisatoshi , Hashikura Kazuaki , Kaneko Taizo , Tanaka Sakae
Published: March 2021

Background

Rotational acetabular osteotomy (RAO) is a type of pelvic osteotomy performed to improve the acetabular bony coverage against the femoral head for patients with acetabular dysplasia. The acetabular bony coverage is ideally evaluated three-dimensionally; however, there is a paucity of published data regarding three-dimensional morphology in patients with long-term excellent outcome after RAO. The present study investigated the characteristics of three-dimensional acetabular morphology with long-term excellent outcome after RAO in comparison to patients with normal hip joints and those converted to total hip arthroplasty (THA) after RAO because of osteoarthritis (OA) progression.

Methods

Anteroposterior plain radiograph and computed tomography data of 57 hip joints (17 joints with excellent outcome 20 years or more after RAO, 16 normal joints, and 20 joints converted to THA after RAO) were analyzed. The two-dimensional lateral center-edge (CE) angle from plain radiographs and acetabular anteversion, anterior acetabular sector angle, and posterior sector angle from computed tomography (CT) images were calculated.

Results

Compared with patients converted to THA, all parameters in patients with long-term excellent outcome after RAO were similar to those in patients with normal hip joints, particularly in the three-dimensional analyses. The anterior bony coverage was excessive, whereas the posterior bony coverage was deficient in patients converted to THA after RAO. Anterior bony impingement and posterior instability may be the cause of OA progression after RAO.

Conclusion

Caution must be taken to avoid rotating the separated fragment excessively to the anterior direction during RAO to prevent OA progression and achieve long-term excellent outcome.
A placental trisomy 2 detected by NIPT evolved in a fetal small Supernumerary Marker Chromosome (sSMC)
Authors: Domaradzka Justyna , Deperas Marta , Obersztyn Ewa , Kucińska-Chahwan Anna , Brison Nathalie , Van Den Bogaert Kris , Roszkowski Tomasz , Kędzior Marta , Bartnik-Głaska Magdalena , Łuszczek Alicja , Jakubów-Durska Krystyna , Vermeesch Joris Robert , Nowakowska Beata Anna
Published: March 2021

Background

Non-invasive prenatal testing (NIPT) is a rapidly developing and widely used method in the prenatal screening. Recently, the widespread use of the NIPT caused a neglecting of the limitations of this technology.

Case presentation

The 38-year-old woman underwent amniocentesis because of a high risk of trisomy 2 revealed by the genome-wide Non-Invasive Prenatal Test (NIPT). The invasive prenatal diagnosis revealed the mosaicism for a small supernumerary marker chromosome sSMC derived from chromosome 2. Interphase fluorescence in situ hybridization (FISH) on uncultured amniocytes revealed three signals of centromere 2 in 30% of the cells. GTG-banded metaphases revealed abnormal karyotype (47,XX,+mar[21]/46,XX[19]) and was confirmed by array comparative genomic hybridization (aCGH). Cytogenetic analyses (FISH, aCGH, karyotype) on fetal skin biopsies were performed and confirmed the genomic gain of the centromeric region of chromosome 2. In the placenta, three cell lines were detected: a normal cell line, a cell line with trisomy 2 and a third one with only the sSMC.

Conclusion

Whole-genome Non-Invasive Prenatal Testing allows not only the identification of common fetal trisomies but also diagnosis of rare chromosomal abnormalities. Especially in such cases, it is extremely important to perform not only NIPT verification on a sample of material other than trophoblast, but also to apply appropriate research methods. Such conduct allows detailed analysis of the detected aberration, thus appropriate clinical validity.
Insulin-like growth factor binding protein 3 promotes radiosensitivity of oral squamous cell carcinoma cells via positive feedback on NF-κB/IL-6/ROS signaling
Authors: Wang Ssu-Han , Chen Yu-Lin , Hsiao Jenn-Ren , Tsai Fang-Yu , Jiang Shih Sheng , Lee Alan Yueh-Luen , Tsai Hui-Jen , Chen Ya-Wen
Published: March 2021

Background

Ectopic insulin-like growth factor binding protein 3 (IGFBP3) expression has been shown to enhance cell migration and lymph node metastasis of oral squamous cell carcinoma (OSCC) cells. However, OSCC patients with high IGFBP3 expression had improved survival compared with those with low expression. Therefore, we speculated that IGFBP3 expression may play a role in response to conventional OSCC therapies, such as radiotherapy.

Methods

We used in vitro and in vivo analyses to explore IGFBP3-mediated radiosensitivity. Reactive oxygen species (ROS) detection by flow cytometry was used to confirm IGFBP3-mediated ionizing radiation (IR)-induced apoptosis. Geneset enrichment analysis (GSEA) and ingenuity pathway analysis (IPA) were used to analyze the relationship between IGFBP3 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling. Assays involving an NF-κB inhibitor, ROS scavenger or interleukin 6 (IL-6) were used to evaluate the NF-κB/IL-6/ROS signaling in IGFBP3-mediated radiosensitivity.

Results

Ectopic IGFBP3 expression enhanced IR-induced cell-killing in vitro. In vivo, IGFBP3 reduced tumor growth and increased apoptotic signals of tumor tissues in immunocompromised mice treated with IR. Combined with IR, ectopic IGFBP3 expression induced mitochondria-dependent apoptosis, which was apparent through mitochondrial destruction and increased ROS production. Ectopic IGFBP3 expression enhanced NK-κB activation and downstream cytokine expression. After IR exposure, IGFBP3-induced NF-κB activation was inhibited by the ROS scavenger N-acetyl-L-cysteine (NAC). IGFBP3-mediated ROS production was reduced by the NF-κB inhibitor BMS-345541, while exogenous IL-6 rescued the NF-κB-inhibited, IGFBP3-mediated ROS production.

Conclusions

Our data demonstrate that IGFBP3, a potential biomarker for radiosensitivity, promotes IR-mediated OSCC cell death by increasing ROS production through NF-κB activation and cytokine production.
Correction to: Multi-modal imaging of high-risk ductal carcinoma in situ of the breast using C2Am: a targeted cell death imaging agent
Authors: Szucs Zoltan , Joseph James , Larkin Tim J. , Xie Bangwen , Bohndiek Sarah E. , Brindle Kevin M. , Neves André A.
Published: March 2021

An amendment to this paper has been published and can be accessed via the original article.
Characterization of the key aroma compounds in three types of bagels by means of the sensomics approach
Authors: Lasekan Ola , Dabaj Fatma , Muniandy Megala , Juhari Nurul Hanisah , Lasekan Adeseye
Published: March 2021

Background

To evaluate the impact of cold fermentation time on bagel rolls, the key aroma-active compounds in the volatile fractions obtained from three different bagel rolls through solvent assisted flavor evaporation (SAFE) were sequentially characterized by an aroma extract dilution analysis (AEDA), quantified by stable isotope dilution and analyzed by odor activity values (OAVs) respectively.

Results

Findings revealed 40 aroma-active compounds with flavor dilution (FD) factor ranges of 2–1024. Of these, 22 compounds (FD ≥ 16) were quantified by stable isotope dilution assays (SIDA). Subsequent analysis of the 22 compounds by odor activity values (OAVs) revealed 14 compounds with OAVs ≥ 1 and the highest concentrations were obtained for 2,3-butanedione, 2-phenylethanol, 3-methylbutanal and acetoin respectively. Two recombination models of the bagels (i.e. 24 h and 48 h bagels) showed similarity to the corresponding bagels. Omission tests confirmed that 2,3-butanedione (buttery), acetoin (buttery), 2-acetyl-1-pyrroline (roasty), 5-methyl-2-furanmethanol (bread-like), (Z)-4-heptenal (biscuit-like) and 4-hydroxy-2,5-dimethyl-3(2H)-furanone, were the key aroma compounds. Additionally, acetic acid, butanoic acid, 2-phenylethanol (honey-like), 3-methylbutanoic acid, 2/3-methylbutanal, vanillin, 3-methylbutanol, methional were also important odorants of the bagel.

Conclusion

Whilst the long, cold fermented bagels exhibited roasty, malty, buttery, baked potato-like, smoky and biscuit-like notes, the control bagels produced similar but less intense odor notes.
Biodiesel production from alternative raw materials using a heterogeneous low ordered biosilicified enzyme as biocatalyst
Authors: Ferrero Gabriel Orlando , Faba Edgar Maximiliano Sánchez , Eimer Griselda Alejandra
Published: March 2021

Background

Cumulative reported evidence has indicated that renewable feedstocks are a promising alternative source to fossil platforms for the production of fuels and chemicals. In that regard, the development of new, highly active, selective, and easy to recover and reuse catalysts for biomass conversions is urgently needed. The combination of enzymatic and inorganic heterogeneous catalysis generates an unprecedented platform that combines the advantages of both, the catalytic efficiency and selectivity of enzymes with the ordered structure, high porosity, mechanical, thermal and chemical resistance of mesoporous materials to obtain enzymatic heterogeneous catalysts. Enzymatic mineralization with an organic silicon precursor (biosilicification) is a promising and emerging approach for the generation of solid hybrid biocatalysts with exceptional stability under severe use conditions. Herein, we assessed the putative advantages of the biosilicification technology for developing an improved efficient and stable biocatalyst for sustainable biofuel production.

Results

A series of solid enzymatic catalysts denominated LOBE (low ordered biosilicified enzyme) were synthesized from Pseudomonas fluorescens lipase and tetraethyl orthosilicate. The microscopic structure and physicochemical properties characterization revealed that the enzyme formed aggregates that were contained in the heart of silicon-covered micelles, providing active sites with the ability to process different raw materials (commercial sunflower and soybean oils, Jatropha excisa oil, waste frying oil, acid oil from soybean soapstock, and pork fat) to produce first- and second-generation biodiesel. Ester content ranged from 81 to 93% wt depending on the raw material used for biodiesel synthesis.

Conclusions

A heterogeneous enzymatic biocatalyst, LOBE4, for efficient biodiesel production was successfully developed in a single-step synthesis reaction using biosilicification technology. LOBE4 showed to be highly efficient in converting refined, non-edible and residual oils (with high water and free fatty acid contents) and ethanol into biodiesel. Thus, LOBE4 emerges as a promising tool to produce second-generation biofuels, with significant implications for establishing a circular economy and reducing the carbon footprint.
Saccharide analysis of onion outer epidermal walls
Authors: Wilson Liza A. , Deligey Fabien , Wang Tuo , Cosgrove Daniel J.
Published: March 2021

Background

Epidermal cell walls have special structural and biological roles in the life of the plant. Typically they are multi-ply structures encrusted with waxes and cutin which protect the plant from dehydration and pathogen attack. These characteristics may also reduce chemical and enzymatic deconstruction of the wall for sugar analysis and conversion to biofuels. We have assessed the saccharide composition of the outer epidermal wall of onion scales with different analytical methods. This wall is a particularly useful model for cell wall imaging and mechanics.

Results

Epidermal walls were depolymerized by acidic methanolysis combined with 2M trifluoracetic acid hydrolysis and the resultant sugars were analyzed by high-performance anion-exchange chromatography with pulsed amperometric detection (HPAEC-PAD). Total sugar yields based on wall dry weight were low (53%). Removal of waxes with chloroform increased the sugar yields to 73% and enzymatic digestion did not improve these yields. Analysis by gas chromatography/mass spectrometry (GC/MS) of per-O-trimethylsilyl (TMS) derivatives of the sugar methyl glycosides produced by acidic methanolysis gave a high yield for galacturonic acid (GalA) but glucose (Glc) was severely reduced. In a complementary fashion, GC/MS analysis of methyl alditols produced by permethylation gave substantial yields for glucose and other neutral sugars, but GalA was severely reduced. Analysis of the walls by 13C solid-state NMR confirmed and extended these results and revealed 15% lipid content after chloroform extraction (potentially cutin and unextractable waxes).

Conclusions

Although exact values vary with the analytical method, our best estimate is that polysaccharide in the outer epidermal wall of onion scales is comprised of homogalacturonan (~ 50%), cellulose (~ 20%), galactan (~ 10%), xyloglucan (~ 10%) and smaller amounts of other polysaccharides. Low yields of specific monosaccharides by some methods may be exaggerated in epidermal walls impregnated with waxes and cutin and call for cautious interpretation of the results.
Eosinophilic fasciitis (Shulman syndrome), a rare entity and diagnostic challenge, as a manifestation of severe chronic graft-versus-host disease: a case report
Authors: Chalopin Thomas , Vallet Nicolas , Morel Marion , Maguet Raphael , d’Alteroche Louis , de Pinieux Gonzague , Hérault Olivier , Gyan Emmanuel , Sutton Laurent , Villate Alban
Published: March 2021

Background

Shulman’s disease, or eosinophilic fasciitis (EF), is a rare autoimmune disease, characterized by sclerodermic skin lesions with progressive induration and thickening of the soft tissues. Chronic graft-versus-host-disease (GVHD) presenting as EF is a very rare manifestation of cutaneous GVHD.

Case presentation

We report an unusual case of EF in a 46-year-old Caucasian male patient who had received an allogenic hematopoietic stem cell transplantation in the context of relapsed/refractory multiple myeloma. The diagnosis was challenging, with the patient presenting hepatic dysfunction, normal eosinophils count, and incomplete clinical signs. Magnetic resonance imaging (MRI) and skin biopsy confirmed the diagnosis of EF. Early initiation of specific treatment with corticosteroids and prednisolone achieved complete response.

Conclusion

In practice, incomplete signs in this rare complication should lead to MRI as it is a major tool to guide decision-making based on the skin biopsy, allowing a rapid diagnosis and the initiation of treatment without delay.