bluuebunny/crossref_metadata_2025 huggingface dataset:
Visualizing Spatial and Stoichiometric Barriers to Bispecific T-Cell Engager Efficacy
Authors: You Ran , Artichoker Jordan , Ray Arja , Gonzalez Velozo Hugo , Rock Dan A. , Conner Kip P. , Krummel Matthew F.
Published: April 2022

Bispecific T-cell engager (BiTE) molecules are biologic T cell–directing immunotherapies. Blinatumomab is approved for treatment of B-cell malignancies, but BiTE molecule development in solid tumors has been more challenging. Here, we employed intravital imaging to characterize exposure and pharmacodynamic response of an anti-muCD3/anti-huEGFRvIII mouse surrogate BiTE molecule in EGFR variant III (EGFRvIII)-positive breast tumors implanted within immunocompetent mice. Our study revealed heterogeneous temporal and spatial dynamics of BiTE molecule extravasation into solid tumors, highlighting physical barriers to BiTE molecule function. We also discovered that high, homogeneous EGFRvIII expression on cancer cells was necessary for a BiTE molecule to efficiently clear tumors. In addition, we found that resident tumor-infiltrating lymphocytes (TIL) were sufficient for optimal tumor killing only at high BiTE molecule dosage, whereas inclusion of peripheral T-cell recruitment was synergistic at moderate to low dosages. We report that deletion of stimulatory conventional type I DCs (cDC1) diminished BiTE molecule–induced T-cell activation and tumor clearance, suggesting that in situ antigen-presenting cell (APC) engagements modulate the extent of BiTE molecule efficacy. In summary, our work identified multiple requirements for optimal BiTE molecule efficacy in solid tumors, providing insights that could be harnessed for solid cancer immunotherapy development.
Simultaneous Detection of Mycobacterium tuberculosis and Atypical Mycobacteria by DNA-Microarray in Egypt
Authors: Gaballah Ahmed , Ghazal Abeer , Almiry Reda , Emad Rasha , Sadek Nadia , Abdel Rahman Mohamed , El-Sherbini Eglal
Published: April 2022

Background and Objectives: Immunocompromised patients are a high-risk group for developing mycobacterial infections with either pulmonary and/or extrapulmonary diseases. Low-cost/density DNA-microarray is considered an easy and efficient method for the detection of typical and atypical mycobacterial species. Materials and Methods: Thirty immunocompromised patients were recruited to provide their clinical specimens (sputum, serum, urine, and lymph node aspirates). Real-time polymerase chain reaction (PCR) and DNA-microarray techniques were performed and compared to the conventional methods of Ziehl-Neelsen staining and Lowenstein Jensen culturing. Results: Mycobacterium tuberculosis complex was detected in all 30 clinical specimens (100% sensitivity) by real-time PCR and DNA-microarray. Additionally, coinfection with 4 atypical species belonging to nontuberculous mycobacteria was identified in 7 sputum specimens. These atypical mycobacterial species were identified as M. kansasii 10% (n = 3), M. avium complex 6.6% (n = 2), M. gordanae 3.3% (n = 1), and M. peregrinum 3.3% (n = 1). Conclusion: This study documents the presence of certain species of atypical mycobacteria among immunocompromised patients in Egypt.
Cost‐Effectiveness of Monitoring Patients Post‐Stroke With Mobile ECG During the Hospital Stay
Authors: Gao Lan , Moodie Marj , Freedman Ben , Lam Christina , Tu Hans , Swift Corey , Ma Sze‐Ho , Mok Vincent C. T. , Sui Yi , Sharpe David , Ghia Darshan , Jannes Jim , Davis Stephen , Liu Xinfeng , Yan Bernard
Published: April 2022

Background

The effectiveness of a nurse‐led in‐hospital monitoring protocol with mobile ECG (iECG) was investigated for detecting atrial fibrillation in patients post‐ischemic stroke or post‐transient ischemic attack. The study aimed to assess the cost‐effectiveness of using iECG during the initial hospital stay compared with standard 24‐hour Holter monitoring.

Methods and Results

A Markov microsimulation model was constructed to simulate the lifetime health outcomes and costs. The rate of atrial fibrillation detection in iECG and Holter monitoring during the in‐hospital phase and characteristics of modeled population (ie, age, sex, CHA2DS2‐VASc) were informed by patient‐level data. Costs related to recurrent stroke, stroke management, medications (new oral anticoagulants), and rehabilitation were included. The cost‐effectiveness analysis outcome was calculated as an incremental cost per quality‐adjusted life‐year gained. As results, monitoring patients with iECG post‐stroke during the index hospitalization was associated with marginally higher costs (A$31 196) and greater benefits (6.70 quality‐adjusted life‐years) compared with 24‐hour Holter surveillance (A$31 095 and 6.66 quality‐adjusted life‐years) over a 20‐year time horizon, with an incremental cost‐effectiveness ratio of $3013/ quality‐adjusted life‐years. Monitoring patients with iECG also contributed to lower recurrence of stroke and stroke‐related deaths (140 recurrent strokes and 20 deaths avoided per 10 000 patients). The probabilistic sensitivity analyses suggested iECG is highly likely to be a cost‐effective intervention (100% probability).

Conclusions

A nurse‐led iECG monitoring protocol during the acute hospital stay was found to improve the rate of atrial fibrillation detection and contributed to slightly increased costs and improved health outcomes. Using iECG to monitor patients post‐stroke during initial hospitalization is recommended to complement routine care.
Towards a moralization of bibliometrics? A response to Kyle Siler
Authors: Gingras Yves
Published: April 2022

In a recent letter to QSS, Kyle Siler (2021), made harsh comments against the decision of the editors to publish a controversial paper signed by Alessandro Strumia (2021) about gender differences in high-energy physics. My aim here is to point to the elements in Siler’s letter that are typical of a new tendency to replace rational and technical arguments with a series of moral statements and ex cathedra affirmations that are not supported by cogent arguments. Such an approach can only be detrimental to rational debates within the bibliometric research community.
Notes on the genus Micropsalliota (Agaricales, Basidiomycota) and the description of a new species from Southern Oman
Authors: AL-KHAROUSI MOZA , HUSSAIN SHAH , AL-MUHARABI MARWA A. , AL-MAQBALI DUA’A , AL-SHABIBI ZAHRA , AL-BALUSHI ABDULLAH H. , AL-YAHYA’EI MOHAMED N. , AL SAADY NADIYA , VELAZHAHAN RETHINASAMY , AL-SADI ABDULLAH M.
Published: April 2022

The genus Micropsalliota is a group of saprotrophic mushrooms, characterized by small to medium-sized basidiomata with fibrillose-squamulose or glabrous pilei, ellipsoid to amygdaliform or cymbiform basidiospores and cheilocystidia that vary in shape from clavate to ventricose or lageniform with more or less a capitate apex. In this study, we described a new species of Micropsalliota from southern Oman. Species description is based on morphological features of basidiomata and phylogenetic analyses of nuc ribosomal DNA internal transcribed spacer (ITS) and D1–D2 domains of the 28S region. The new species Micropsalliota ventricocystidiata is characterized by a medium-sized basidiomata, with plano-convex pileus, covered with reddish-brown squamules and basidiospores are ellipsoid to amygdaliform with acute apex in side view and oblong in face view, measuring 7.5–8.5 × 4.5–5 µm. Morphological comparison of M. ventricocystidiata with respect to other species of the genus is provided. We discussed that species of the genus can be divided into two groups based on their pileus morphology and basidiospores size.
Practitioners’ Curriculum Conceptualization and Their Professional Participation in Curriculum Development and Implementation in Ethiopia
Authors: Molla Amsalu , Melesse Solomon , Melesse Tadese
Published: April 2022

The purpose of this paper was to review practitioners’ conception and involvement in the curriculum development and implementation process. Different empirical works done in Ethiopia and reflections of lived experiences of the researchers were used as sources of this review. The results revealed that the dominant curriculum conceptualization of the practitioners was found to be consistent with the technical procedural curriculum conception. The participation of practitioners in Ethiopia faced varied challenges including academic qualification, power imposition, and failure to consider curriculum as a practical and a phenomenological study. Finally, the researchers forwarded relevant recommendations as detailed in the text.
Moderating Role of Self-Compassion in the Relationships Between the Three Forms of Perfectionism with Anger, Aggression, and Hostility
Authors: Abdollahi Abbas , Gardanova Zhanna R. , Ramaiah Pushpamala , Zainal Anna Gustina , Abdelbasset Walid Kamal , Asmundson Gordon J. G. , Chupradit Supat , Sultonov Shokhrukh Kh , Pashanova Olga V. , Iswanto A. Heri
Published: April 2022

The prevalence of aggression in adolescents is on the rise, and it could be a serious public health concern. Studies have found positive relationships between perfectionism with anger, aggression, and hostility. However, the moderating role of self-compassion in the links between perfectionism with anger, aggression, and hostility has not been studied. To better understand the relationships between the three forms of perfectionism with anger, aggression, and hostility, this study aimed to explore the moderating role of self-compassion. Participants were 380 undergraduates selected using a multi-stage cluster sampling technique from three universities in Iran. Participants completed the Self-Compassion Scale, the Multidimensional Perfectionism Scale, and the Aggression Questionnaire Scale. The results from structural equation modelling analysis showed that other-oriented perfectionism and socially prescribed perfectionism positively predicted anger, aggression, and hostility. The results showed that self-oriented perfectionism significantly and positively predicted anger and hostility; but there were no observed statistically significant relationships of self-oriented perfectionism with verbal aggression and physical aggression. The findings showed that self-compassion played a moderating role in the relationships between other-oriented perfectionism and socially prescribed perfectionism with anger, aggression, and hostility; however, it did not play a moderating effect on self-oriented perfectionism with anger, aggression, and hostility. The findings provide a deeper understanding of the moderating role of self-compassion in the links between other-oriented perfectionism and socially prescribed perfectionism with anger, aggression, and hostility among undergraduates. The findings of this study could be applicable for psychologists and counselors who deal with aggressive behavior, anger, and hostility in undergraduate students to assess the three forms of perfectionism and self-compassion.
Contributing Factors in the Successful Repatriation of Long-Term Adult Christian Missionaries
Authors: Zavala-Barajas Shelby L. , Eltiti Stacy , Crawford Nancy
Published: April 2022

Literature indicates that mental health, time spent on mission, and reverse culture shock are all factors in Christian missionaries successful repatriation. The present study explored the effect of time since return, social support, and reverse culture shock on levels of depression, anxiety, and stress in long-term adult Christian missionaries during the repatriation process. I all, 31 Christian missionaries completed self-report measures of social support, reverse culture shock, depression, anxiety, and stress. Results showed that the longer an individual had been back in their passport country significantly correlated with lower levels of depression. In addition, higher levels of reverse culture shock correlated with higher levels of depression and stress. Although social support did not moderate the relationship between reentry shock and well-being, in open-ended questions, respondents indicated how valuable social support was to them in the repatriation process. Implications for sending agencies and clinicians working with repatriating adult Christian missionaries are discussed.
Loving strangers, avoiding risks: Online dating practices and scams among Chinese lesbian (lala) women
Authors: Tao Han
Published: April 2022

The proliferating online social networking sites have created opportunities for Chinese queer women to meet new friends and lovers; yet, research on lesbian online dating in mainland China is scarce compared to heterosexual and gay online dating. This article investigates lesbian/ lala women’s online dating experiences in the context of economic reforms and the trust crisis in urban China. It is based on 16 in-depth interviews and ethnographic fieldwork in Guangdong from June 2018 to July 2019. It focuses on two digital platforms: Douban Group and WeChat. This article explores how online anonymity and stranger sociality shaped queer women’s moral practices regarding turning virtual strangers into real-life partners. Queer women in this research expressed concerns about being cheated by low quality( suzhi) lovers, swindlers, and married women. This article suggests that the emerging online stranger sociality has both enabled and constrained lesbian/ lala women’s practice of seeking loving relationships, while they must internalize the potential risks by themselves.
Variable thickness thin-walled rotating blades made of functionally graded porous materials
Authors: Farsadi Touraj
Published: April 2022

Within this study, the statics and dynamics performance of turbomachinery variable thickness rotating blades, composed of thin-walled, functionally graded metal-ceramic materials including cross-sectional distributed porosity is optimized. The pre-twisted, tapered, Thin-Wall Rotating Beams (TWRB) with constant angular velocity are considered within this context. For the optimization purpose, a genetic algorithm (GA) is implemented in a nonlinear constraint optimization problem. The goal is to exploit desirable thickness variations with improved dynamic, static, and buckling behavior of the variable thickness functionally graded material (FGM) blades. Hamilton’s principle was applied using the Euler–Lagrange dynamic system of governing equation, while the extended Galerkin’s method (EGM) was applied to solve the equations. Two variables in thickness function for each wall of the beam box (a total of eight variables) are considered in the optimization procedure. The effects of some parameters, such as the FGM volume fraction exponent, angular velocity, the pre-twist angle, porosity coefficient, and taper ratios on the mechanical behavior of the variable thickness FG beams are studied. The optimization result shows that applying the variable thickness concept can significantly increase the 1st and 2nd natural frequencies (by 60.4%, 60.22%) and reduce the weight (by 31.05%) of the system compared to the reference constant thickness beam while the increase in chordwise and flapwise deformations (by 8.16%, 9.93%) under combined loading is in an acceptable range, respectively.
Treatment with low-dose prednisone in refractory obstetric antiphospholipid syndrome: A retrospective cohort study and meta-analysis
Authors: Riancho-Zarrabeitia Leyre , Lopez-Marin Laura , Cacho Pedro Muñoz , López-Hoyos Marcos , Barrio Rafael del , Haya Ana , Martínez-Taboada Víctor M
Published: April 2022

Background

Glucocorticoids have been suggested as a potential therapy in refractory obstetric antiphospholipid syndrome (oAPS). Our aims were to describe a cohort of patients with oAPS treated with low-dose glucocorticoids and to perform a systematic review and meta-analysis evaluating the effects of additional glucocorticoids on the pregnancy outcomes in oAPS patients.

Methods

Retrospective study that included 11 women diagnosed with primary antiphospholipid syndrome. The meta-analysis was conducted by fitting random effects models and was checked for heterogeneity.

Results

All women had suffered from early pregnancy losses and two also had a history of fetal deaths. We studied 47 pregnancies that resulted in 32 abortions (68.1%) and 3 fetal deaths (6.4%). Twenty-six pregnancies were under treatment, mainly LDA and LMWH. Low-dose glucocorticoids were indicated in 13 pregnancies (always in association with LDA and LMWH). There was a decrease in pregnancy loss in those patients treated with LDA and LMWH. Treatment with glucocorticoids significantly increased the rate of successful pregnancy (38.5% abortions in treated vs 85.3% abortions in non-treated pregnancies; p=0.003). After multivariate GEE analysis, only glucocorticoids remained inversely associated with pregnancy loss (OR=0.157, (CI 0.025–0.968, p=0.046)). The meta-analysis showed that glucocorticoids tended to improve the frequency of successful pregnancy (OR= 0.509 (0.252–1.028), p=0.06). Three cases of gestational diabetes and one of preeclampsia were observed in our cohort. The meta-analysis, which mostly included studies using high-dose steroids, showed that glucocorticoids increased not only the frequency of preeclampsia and gestational diabetes, but also the rate of pre-term birth.

Conclusions

The efficacy of low-dose glucocorticoids in addition to the standard therapy in patients with refractory oAPS should be confirmed in well-designed clinical trials. However, high doses of steroids significantly increase the frequency of maternal and fetal morbidities, making their use strongly inadvisable.
2019 ACR/EULAR classification criteria and therapy in predicting organ damage accrual in patients with childhood-onset systemic lupus erythematosus: A retrospective study over the last 29 years
Authors: Kifer Nastasia , Sestan Mario , Frkovic Marijan , Kifer Domagoj , Kozmar Ana , Padjen Ivan , Potocki Kristina , Anic Branimir , Batinic Drago , Malcic Ivan , Jelusic Marija
Published: April 2022

Objective

We explored damage occurrence in patients with childhood-onset SLE (cSLE) and aimed to predict the risk of organ damage occurrence in time.

Methods

The retrospective study included patients treated for cSLE at the Centre of Reference for Pediatric and Adolescent Rheumatology of the Republic Croatia over a 29-year period.

Results

The disease development of 97 patients (77 females) with cSLE was examined. The median (Q1, Q3) follow-up time was 6.5 (2.3, 12.0) years. SDI was determined at 5 time points (6, 12, 24, 36 months, and last follow-up). Thirty-eight patients (48%) had organ damage at the last follow-up. Prepubertal group of patients showed higher SLEDAI scores at the disease onset, while post-pubertal group had significantly lower proportion of patients with relapses. We estimated the time from the first symptom to the moment of damage and our findings suggest that it is unlikely that organ damage will occur in 50% of patients in the first 6 years since the diagnosis. The number of 2019 ACR/EULAR classification criteria at the time of diagnosis associated with SDI determined after 1 year of the follow-up period. The patients who received higher doses of glucocorticoids accumulated damage faster and mycophenolate mofetil was found to be a more frequent therapy in patients with SDI ≥3.

Conclusion

Knowing that damage will most likely happen after the first 6 years after diagnosis in 50% of patients enables physicians to better predict damage occurrence. High number of 2019 ACR/EULAR criteria and treatment with glucocorticoids in childhood-onset SLE are associated with damage accrual and these findings could enable us to detect patients which should be closely monitored for higher risk of damage development.
Parricide, Mental Illness, and Parental Proximity: The Gendered Contexts of Parricide in England and Wales
Authors: Miles Caroline , Condry Rachel , Windsor Elspeth
Published: April 2022

Parricide is underresearched in the UK, and the contexts of this gendered form of violence are poorly understood. Heide’s typology provides an advanced understanding of parricide in the United States, where the majority of parent-killings involve firearms. This article develops a UK-based analysis of the contexts of parricide, combining national statistics with police case study data ( n = 57) and case review data ( n = 21). Our findings indicate that mental illness plays a key role, combined with a gendered context of “parental proximity” and the simultaneous responsibilization and marginalization of parent-victims (particularly mothers), supporting the need for feminist analyses of parricide.
Occurrence, Antibiotic Susceptibility and Genes Encoding Antibacterial Resistance of Salmonella spp. and Escherichia coli From Milk and Meat Sold in Markets of Bushenyi District, Uganda
Authors: Onohuean Hope , Igere Bright E
Published: April 2022

The bacteriological safety of food/food products and the menace of antimicrobial resistance amongst enteropathogenic bacteria raise therapeutic management concerns within the public health system. Recently consumers of food/food products purchased from the public market of Bushenyi District presents with Enterobacteriaceae infection-associated symptoms and clinical conditions. We determine the molecular characterization and antibiotic signatures of some enteric bacterial recovered from foods/food products in markets of Bushenyi District, Uganda. Standard molecular biology techniques (Polymerase chain reaction PCR) and microbiological procedures were applied. Meat (MT) and milk (MK) samples were collected from 4 communities/town markets (Kizinda, Ishaka, Bushenyi, kashenyi) between April and September 2020 and analyzed. Our result reveals high differential counts of Salmonella species (175.33 ± 59.71 Log 10 CFU/100 ml) and Escherichia coli (53.33 ± 26.03 Log 10 CFU/100 ml) within the 4 markets with the count of Salmonella species higher than that of E. coli in each sampled market. The PCR further confirmed the detected strains (22.72% of E. coli and 54.29% of Salmonella species) and diverse multiple antibiotic-resistant determinants {TEM: (12 (23.1%) blaTEM-2 gene, 3 (5.8%) blaTEM gene}, 5 (9.6%) blaSHV gene, 3 (5.8%) bla-CTX-M-2, 1 (1.9%) bla-CTX-M-9 }. Other resistance genes detected were {10 (21.7%) strA gene} and 8 (17.4%) aadA gene} indicating a potential antibiotic failure. The need for alternative medicine and therapeutic measure is suggestive. Astute and routine surveillance/monitoring of potential pathogens and food products in the public market remains a core for maintaining future consumer safety.
Molecular Identification of Infectious Enteropathogens in Faeces of Healthy Horses
Authors: Paruch Lisa , Paruch Adam M
Published: April 2022

Zoogenic faecal contamination of the environment is one of the indices included in the evaluation of ecological threats, health hazards and adverse impacts on various ecosystems. The risks and environmental concerns are associated with the fact that faeces of wild and domesticated animals constitute the largest source of environmental loading of enteropathogens associated with transmission of zoonotic diseases (enteric zoonoses). Although sick animals are more likely to transmit pathogens, healthy ones can also be the carriers and defecate them into the environment. This is of particular importance given the close human-animal interactions and health effects resulting from human and ecological exposures to faecal hazards from companion and farm animals. We have therefore set out to investigate whether healthy equines can carry and defecate human infectious pathogens. For this purpose, we set up a pilot study to examine the faecal DNA of horses using culture-independent molecular diagnostics – fluorescent probe-based quantitative real-time PCR. Our results revealed that among a total of 23 horses, 6 were found to carry Campylobacter jejuni ( C. jejuni), and 5 had Salmonella enterica serovar Typhimurium ( S. Typhimurium). Moreover, Enterococcus faecalis ( E. faecalis) was found in 14 horses, while 19 were positive for Clostridium perfringens ( C. perfringens). Furthermore, the frequently reported protozoan parasites in livestock, Cryptosporidium parvum ( C. parvum) and Giardia lamblia ( G. lamblia), were discovered in 8 and 7 samples, respectively. This pilot study shed new light on the phenomenon of healthy horses carrying C. jejuni and other human-health-related enteropathogens.
Perpetual scrutiny? Mutual control among coalition political parties in the executive and parliamentary phases of law-making
Authors: Zbíral Robert , Lysek Jakub , Bílek Jaroslav
Published: April 2022

There is an ongoing debate on how political parties that form coalition governments keep tabs on each other during the drafting and negotiation of new bills. Our article complements existing studies focused on the parliamentary stage of law-making by enriching current knowledge with an analysis of the executive phase, where bills may be significantly changed before they are submitted to the legislature. Contrary to theoretical expectations, results based on unique data from the Czech Republic reveal that bills which are heavily altered during the executive phase are subsequently significantly changed in the parliament. Additional interaction models indicate the effect is stronger for bills that are highly significant for the proposing minister and are a greater distance from any coalition compromise. Our findings open the question of why the coalition parties leave the resolution of some controversial issues to the parliamentary phase: the outstanding conflict may be genuine, or the coalition MPs may just be playing out a prearranged and staged battle that enables the coalition partners to show their distinctive qualities to the voters.
The role of language control in cross-language phoneme processing: Evidence from Chinese–English bilinguals
Authors: Zuo Mingyue , Schwieter John W. , Cao Ningning , Liu Huanhuan
Published: April 2022

Aims:

Cross-language interference studies of language control mainly focus on the lexical level, whereas language control may occur at the smallest unit phonemic level of language. In the present study, we examined the role of language control during cross-language phoneme processing.

Design:

Participants used one language to name pinyin or alphabet in the single-language blocks, and they used two languages for naming in the mixed-language blocks.

Data and analysis:

Using a linear mixed-effects model, we built models for mixing costs and switching costs based on reaction times (RTs) and accuracy.

Findings:

Switching between Chinese (L1) and English (L2) phonetic symbols revealed both mixing and switching costs.

Originality:

The findings suggest that switching of cross-language phonemes requires not only global control of the non-target phonemes, but also local control of the non-target phonemes.

Significance:

Just as cross-language interference control occurs at the lexical level, this study demonstrates that control also occurs at the phonemic level.
Two coordination polymers: Crystal structures, prevention and nursing values on postoperative infection
Authors: Ding Meng , Yang Fan , Lv Qingquan , Liu Qiongfang
Published: April 2022

In this current work, two fresh transition metal coordination polymers (CPs) have been created with the reaction between terphenyl-3,3″,5,5″-tetracarboxylic acid (H4L), the symmetrical rigid carboxylic acid ligand and the relevant metal salts under the reaction conditions of solvothermal, and the chemical compositions of the compounds respectively are {[Cu2(TPTC) (DMF)2(H2O)]·2DMF·2H2O} (2) and {[Zn (TPTC) (1,2-bimb)2]·4(H2O)}n (1, bimb = 1,2-bis((1H-imidazol-1-yl)methyl)benzene). Moreover, the prevention and nursing values of the compound on postoperative infection was explored and their corresponding mechanism also was investigated. Firstly, enzyme linked immunosorbent assay kit (ELISA) was employed to detect the release of inflammatory cytokines into plasma. Additionally, the expression of the bacterial survival genes was determined via exploiting the real time reverse transcription-polymerase chain reaction (RT-PCR) after treated with the compound.
Come As You Are – Small Groups in an Online Statistics Course for Highly Heterogeneous Students
Authors: Schützler Lena , Christ Oliver
Published: April 2022

Statistics is not the subject most psychology students are feverishly looking forward to. Fears and doubts about its relevance are quite common. This is especially pronounced at our institution, a large distance-teaching university with highly heterogeneous students. We recognized three clusters of students that might need special support: (1) students with fear of statistics, (2) students whose school time was a long time ago, (3) students who already failed the statistics exam. We gave those students the opportunity to participate in small, supervised groups to discuss learning strategies, problems, or fears. Students who did not participate served as a control group. We exploratively evaluated which kind of students were interested, and if the groups affected attitudes towards statistics, general self-efficacy, and exam-related variables. Interest and activity in the groups were low. No unique effect of participation in the groups on attitudes and grades were observable. Students stated that the groups did not help them to deal with the course. If these results prove stable in further studies with an improved design, one might conclude that setting up such small groups is not worth the effort.
Family conflict and aggression in the paediatric intensive care unit: Responding to challenges in practice
Authors: Basu Shreerupa , Preisz Anne
Published: April 2022

The paediatric intensive care unit (PICU) is a high-stress environment for parents, families and health care professionals (HCPs) alike. Family members experiencing stress or grief related to the admission of their sick child may at times exhibit challenging behaviours; these exist on a continuum from those that are anticipated in context, through to unacceptable aggression. Rare, extreme behaviours include threats, verbal or even physical abuse. Both extreme and recurrent ‘subthreshold’ behaviours can cause significant staff distress, impede optimal clinical care and compromise patient outcomes. The unique PICU environment and model of care may magnify stressors for both families and staff and the family-centred approach to care (FCC) central to paediatric practice, may also contribute to contextual challenges. Pervasive conflict in paediatric healthcare is harmful for patients, families, PICU staff and the institution more broadly. We propose that caring for children and caring for staff are inseparable goals and the latter has been inadvertently but detrimentally deprioritised as FCC has become a primary focus. A transparent and graded hierarchy of responses to variable levels of challenging behaviour is necessary to ensure that families are supported, while HCPs remain protected in the workplace. This requires establishing firm limits supported by all teams and levels of the institution. As such, we aim to identify and clarify the context and impact of challenging parent and family behaviour in the PICU and to offer potential, proactive mitigation strategies, based on reflections and stakeholder discussion following recent clinical challenges and experiences in our unit.
Analyses of lung cancer-derived volatiles in exhaled breath and in vitro models
Authors: Choueiry Fouad , Barham Addison , Zhu Jiangjiang
Published: April 2022

Lung cancer is one of the leading causes of cancer incidence and cancer-related deaths in the world. Early diagnosis of pulmonary tumors results in improved survival compared to diagnosis with more advanced disease, yet early disease is not reliably indicated by symptoms. Despite of the improved testing and monitoring techniques for lung cancer in the past decades, most diagnostic tests, such as sputum cytology or tissue biopsies, are invasive and risky, rendering them unfeasible for large population screening. The non-invasive analysis of exhaled breath has gained attentions as an innovative screening method to measure chemical alterations within the human volatilome profile as a result of oncogenesis. More importantly, volatile organic compounds (VOCs) have been correlated to the pathophysiology of disease since the source of volatile compounds relies mostly on endogenous metabolic processes that are altered as a result of disease onset. Therefore, studying VOCs emitted from human breath may assist lung cancer diagnosis, treatment monitoring, and other surveillance of this devastating disease. In this mini review, we evaluated recent human studies that have attempted to identify lung cancer-derived volatiles in exhaled breath of patients. We also examined reported volatiles in cell cultures of lung cancer to better understand the origins of cancer-associated VOCs. We highlight the metabolic processes of lung cancer that could be responsible for the endogenous synthesis of these VOCs and pinpoint the protein-encoding genes involved in these pathways. Finally, we highlight the potential value of a breath test in lung cancer and propose prominent areas for future research required for the incorporation of VOCs-based testing into clinical settings.
The emerging role of cross-resistance between taxanes and AR-targeting therapy in metastatic prostate cancer
Authors: Yao Kang , Li Shun , Liu Qingyong , Wu Fei
Published: April 2022

Background:

To date, the number of prostate cancer ranked first among newly diagnosed malignant tumors in men from multiple countries. Localized prostate cancer could be controlled by curative therapy. However, for patients with metastatic prostate cancer (mPC), the prognosis is poor. As among first-line treatments of systemic therapies for mPC, docetaxel and androgen receptor (AR)-targeted therapies have been widely used. However, mPC patients inevitably developed resistance to the current therapy. More importantly, there is a cross-resistance between docetaxel-based chemotherapy and AR-targeting therapy during the treatment process, which could impair the overall survival benefits without proper administration.

Objective:

Therefore, it is urgent to elucidate the mechanism of cross-resistance and explore the optimal sequential strategy.

Methods:

Here, in this review, we systematically reviewed and summarised the updated literature on clinical evidence and mechanistic research of treatment resistance in mPC.

Results:

Emerging evidence indicated that AR splice variants, AR overexpression or mutations, AR nuclear translocation, as well as AR signaling reactivation collectively contributed to the cross-resistance. With the current understanding of cross-resistance, multiple solutions are promising for improving the benefits, including refining the sequencing of available therapies for mPC, in combination with potential targeted inhibitors or immune checkpoint inhibitors. Further studies are needed to explore the combination of emerging strategies and eventually control the progression of prostate cancer.

Conclusions:

This review defined the mutual and unique resistant mechanism of these treatments, which might help to focus and accelerate therapeutic research that may ultimately improve clinical outcomes for patients with prostate cancer.

Level of evidence:

Not applicable
A complex proinflammatory cascade mediates the activation of HSCs upon LPS exposure in vivo
Authors: Demel Uta Margareta , Lutz Raphael , Sujer Stefanie , Demerdash Yasmin , Sood Shubhankar , Grünschläger Florian , Kuck Andrea , Werner Paula , Blaszkiewicz Sandra , Uckelmann Hannah Julia , Haas Simon , Essers Marieke Alida Gertruda
Published: April 2022

Infections are a key source of stress to the hematopoietic system. While infections consume short-lived innate immune cells, their recovery depends on quiescent hematopoietic stem cells (HSCs) with long-term self-renewal capacity. Both chronic inflammatory stress and bacterial infections compromise competitive HSC capacity and cause bone marrow (BM) failure. However, our understanding of how HSCs act during acute and contained infections remains incomplete. Here, we used advanced chimeric and genetic mouse models in combination with pharmacological interventions to dissect the complex nature of the acute systemic response of HSCs to lipopolysaccharide (LPS), a well-established model for inducing inflammatory stress. Acute LPS challenge transiently induced proliferation of quiescent HSCs in vivo. This response was not only mediated via direct LPS-TLR4 conjugation on HSCs but also involved indirect TLR4 signaling in CD115+ monocytic cells, inducing a complex proinflammatory cytokine cascade in BM. Downstream of LPS-TLR4 signaling, the combined action of proinflammatory cytokines such as interferon (IFN)α, IFNγ, tumor necrosis factor-α, interleukin (IL)-1α, IL-1β, and many others is required to mediate full HSC activation in vivo. Together, our study reveals detailed mechanistic insights into the interplay of proinflammatory cytokine-induced molecular pathways and cell types that jointly orchestrate the complex process of emergency hematopoiesis and HSC activation upon LPS exposure in vivo.
A comparison of topologically associating domain callers over mammals at high resolution
Authors: Sefer Emre
Published: April 2022

Background

Topologically associating domains (TADs) are locally highly-interacting genome regions, which also play a critical role in regulating gene expression in the cell. TADs have been first identified while investigating the 3D genome structure over High-throughput Chromosome Conformation Capture (Hi-C) interaction dataset. Substantial degree of efforts have been devoted to develop techniques for inferring TADs from Hi-C interaction dataset. Many TAD-calling methods have been developed which differ in their criteria and assumptions in TAD inference. Correspondingly, TADs inferred via these callers vary in terms of both similarities and biological features they are enriched in.

Result

We have carried out a systematic comparison of 27 TAD-calling methods over mammals. We use Micro-C, a recent high-resolution variant of Hi-C, to compare TADs at a very high resolution, and classify the methods into 3 categories: feature-based methods, Clustering methods, Graph-partitioning methods. We have evaluated TAD boundaries, gaps between adjacent TADs, and quality of TADs across various criteria. We also found particularly CTCF and Cohesin proteins to be effective in formation of TADs with corner dots. We have also assessed the callers performance on simulated datasets since a gold standard for TADs is missing. TAD sizes and numbers change remarkably between TAD callers and dataset resolutions, indicating that TADs are hierarchically-organized domains, instead of disjoint regions. A core subset of feature-based TAD callers regularly perform the best while inferring reproducible domains, which are also enriched for TAD related biological properties.

Conclusion

We have analyzed the fundamental principles of TAD-calling methods, and identified the existing situation in TAD inference across high resolution Micro-C interaction datasets over mammals. We come up with a systematic, comprehensive, and concise framework to evaluate the TAD-calling methods performance across Micro-C datasets. Our research will be useful in selecting appropriate methods for TAD inference and evaluation based on available data, experimental design, and biological question of interest. We also introduce our analysis as a benchmarking tool with publicly available source code.
COX-2 strengthens the effects of acid and bile salts on human esophageal cells and Barrett esophageal cells
Authors: Jiangang Shen , Nayoung Kang , Hongfang Wang , Junda Li , Li Chen , Xuefeng Bai , Mingsong Li
Published: April 2022

Aims

Investigate the effect and mechanism of COX-2 on viability, intestinal metaplasia, and atypia in human esophageal squamous and Barrett esophageal cell lines.

Methods

Human esophageal squamous and Barrett esophageal cell lines were transfected with a COX-2 expression vector and a COX-2 siRNA, and then were treated with acid, bile salts, and a mixture of both. Cell viability, the expression of COX-2, NF-κB(p65), CDX-2, MUC2, c-myb, and BMP-4, and the morphology and microstructure of cells were then observed.

Results

The viability of COX-2 overexpressed cells was significantly higher than that of control cells, while the viability of COX-2 siRNA-treated cells was significantly lower than that of control cells. Intestinal metaplasia and atypia were observed in cells overexpressing COX-2. Acid, bile salts, and their mixture inhibited the viability of these two cell lines, but the inhibitory effect of the mixture was stronger than a single treatment in either. SiRNA mediated knockdown of COX-2 strengthened the antiproliferative effects of the mixture on HET-1A and BAR-T cells. The expression of p-p65, CDX-2, and BMP-4 was positively correlated with COX-2 expression, while the expression levels of p65, MUC2, and c-myb remained unchanged.

Conclusion

COX-2 may influence the viability, atypia, and intestinal metaplasia of human esophageal cells and Barrett esophageal cells. Activation of the p-p65, CDX-2, and BMP-4 signaling pathways by COX-2 may be part of this mechanism.
Standard rectal swabs as a surrogate sample for gut microbiome monitoring in intensive care
Authors: Schlebusch Sanmarié , Graham Rikki M. A. , Jennison Amy V. , Lassig-Smith Melissa M. , Harris Patrick N. A. , Lipman Jeffrey , Ó Cuív Páraic , Paterson David L.
Published: April 2022

Background

The purpose of this study was to investigate the use of routinely available rectal swabs as a surrogate sample type for testing the gut microbiome and monitoring antibiotic effects on key gut microorganisms, of patients hospitalised in an intensive care unit. A metagenomic whole genome sequencing approach was undertaken to determine the diversity of organisms as well as resistance genes and to compare findings between the two sampling techniques.

Results

No significant difference was observed in overall diversity between the faeces and rectal swabs and sampling technique was not demonstrated to predict microbial community variation. More human DNA was present in the swabs and some differences were observed only for a select few anaerobes and bacteria also associated with skin and/or the female genitourinary system, possibly reflecting sampling site or technique. Antibiotics and collections at different times of admission were both considered significant influences on microbial community composition alteration. Detection of antibiotic resistance genes between rectal swabs and faeces were overall not significantly different, although some variations were detected with a potential association with the number of human sequence reads in a sample.

Conclusion

Testing the gut microbiome using standard rectal swab collection techniques currently used for multi-resistant organism screening has been demonstrated to have utility in gut microbiome monitoring in intensive care. The use of information from this article, in terms of methodology as well as near equivalence demonstrated between rectal swabs and faeces will be able to support and potentially facilitate the introduction into clinical practice.
Plastome structure, phylogenomics and evolution of plastid genes in Swertia (Gentianaceae) in the Qing-Tibetan Plateau
Authors: Cao Qian , Gao Qingbo , Ma Xiaolei , Zhang Faqi , Xing Rui , Chi Xiaofeng , Chen Shilong
Published: April 2022

Background

The genus Swertia is of great medicinal importance and one of the most taxonomically challenging taxa within Gentianaceae, largely due to the morphological similarities of species within this genus and with its closely related genera. Previous molecular studies confirmed its polyphyly but suffered from low phylogenetic resolutions because only limited sequence loci were used. Thus, we conducted the structural, gene evolutionary, and phylogenetic analyses of 11 newly obtained plastomes of Swertia. Our result greatly improved the phylogenetic resolutions in Swertia, shed new light on the plastome evolution and phylogenetic relationships of this genus.

Results

The 11 Swertia plastomes together with the published seven species proved highly similar in overall size, structure, gene order, and content, but revealed some structural variations caused by the expansion and contraction of the IRb region into the LSC region, due to the heterogeneous length of the ψycf1. The gene rps16 was found to be in a state flux with pseudogenes or completely lost. Similar situation was also documented in other genera of Gentianaceae. This might imply loss of the gene in the common ancestor of Gentianaceae. The distribution plot of ENC vs. GC3 showed all these plastomes arranging very close in the Wright line with an expected ENC value (49–52%), suggesting the codon usage of Swertia was mainly constrained by a GC mutation bias. Most of the genes remained under the purifying selection, however, the cemA was identified under positive selection, possibly reflecting an adaptive response to low CO2 atmospheric conditions during the Late Miocene. Our phylogenomic analyses, based on 74 protein-coding genes (CDS), supported the polyphyly of Swertia with its close allies in the subtribe Swertiinae, presumably due to recent rapid radiation. The topology inferred from our phylogenetic analyses partly supported the current taxonomic treatment. Finally, several highly variable loci were identified, which can be used in future phylogenetic studies and accurate identification of medicinal genuineness of Swertia.

Conclusions

Our study confirmed the polyphyly of Swertia and demonstrated the power of plastome phylogenomics in improvement of phylogenetic resolution, thus contributing to a better understanding of the evolutionary history of Swertia.
Serum total bilirubin and long-term prognosis of patients with new-onset non-ST elevation myocardial infarction: a cohort study
Authors: Yang Yi , Wang Jun , Wai Si Ding A Ji Gu Li , Xu Yanan , Jiang Haibing , Ma Kezhong , Zhu Tongjian
Published: April 2022

Background

The potential prognostic role of total bilirubin (TBIL) in patients with new-onset non-ST elevation myocardial infarction (NSTEMI) is not fully understood. This study aims to evaluate the potential predictive value of TBIL for long-term prognosis in patients with new-onset NSTEMI.

Methods

Patients with new-onset NSTEMI that underwent emergency coronary angiography in our department from June 2015 to March 2020 were included. Baseline TBIL was measured at admission. SYNTAX scores were used to indicate the severity of coronary lesions. The association between TBIL and SYNTAX scores was analyzed using multivariate logistic regression. The patients were followed for the incidence of major adverse cardiac and cerebrovascular events (MACCEs). The association between TBIL and MACCEs was analyzed using Kaplan–Meier survival methods.

Results

In total 327 patients were included in this study. Patients were divided according to tertiles of TBIL (first tertile < 10.23 µmol/L, n = 109; second tertile 10.23–14.30 µmol/L, n = 109; and third tertile ≥ 14.30 µmol/L, n = 109). TBIL was independently associated with the severity of coronary lesions in patients with NSTEMI, with an adjusted odds ratio (OR) and 95% confidence interval (CI) for the third tertile and the second tertile compared with the first tertile of TBIL of 2.259 (1.197–4.263) and 2.167 (1.157–4.059), respectively (both p < 0.05). After a mean follow-up of 30.33 months, MACCE had occurred in 57 patients. TBIL was independently associated with the increased risk of MACCEs, with an adjusted hazard ratio (HR) and 95% CI for the third tertile and the second tertile compared with the first tertile of TBIL of 2.737 (1.161–6.450) and 3.272 (1.408–7.607), respectively (both p < 0.05).

Conclusions

Higher myocardial infarction admission TBIL might independently predict poor prognosis in patients with NSTEMI.