bluuebunny/crossref_metadata_2025 huggingface dataset:
Recombination rates in pigs differ between breeds, sexes and individuals, and are associated with the RNF212, SYCP2, PRDM7, MEI1 and MSH4 loci
Authors: Brekke Cathrine , Berg Peer , Gjuvsland Arne B. , Johnston Susan E.
Published: May 2022

Background

Recombination is a fundamental part of mammalian meiosis that leads to the exchange of large segments of DNA between homologous chromosomes and is therefore an important driver of genetic diversity in populations. In breeding populations, understanding recombination is of particular interest because it can break up unfavourable linkage phases between alleles and produce novel combinations of alleles that could be exploited in selection. In this study, we used dense single nucleotide polymorphism (SNP) genotype data and pedigree information to analyse individual and sex-specific variation and genetic architecture of recombination rates within and between five commercially selected pig breeds.

Results

In agreement with previous studies, recombination rates were higher in females than in males for all breeds and for all chromosomes, except 1 and 13, for which male rates were slightly higher. Total recombination rate differed between breeds but the pattern of recombination along the chromosomes was well conserved across breeds for the same sex. The autosomal linkage maps spanned a total length of 1731 to 1887 cM for males and of 2231 to 2515 cM for females. Estimates of heritability for individual autosomal crossover count ranged from 0.04 to 0.07 for males and from 0.08 to 0.11 for females. Fourteen genomic regions were found to be associated with individual autosomal crossover count. Of these, four were close to or within candidate genes that have previously been associated with individual recombination rates in pigs and other mammals, namely RNF212, SYCP2 and MSH4. Two of the identified regions included the PRDM7 and MEI1 genes, which are known to be involved in meiosis but have not been previously associated with variation in individual recombination rates.

Conclusions

This study shows that genetic variation in autosomal recombination rate persists in domesticated species under strong selection, with differences between closely-related breeds and marked differences between the sexes. Our findings support results from other studies, i.e., that individual crossover counts are associated with the RNF212, SYCP2 and MSH4 genes in pig. In addition, we have found two novel candidate genes associated with the trait, namely PRDM7 and MEI1.
A comprehensive study on size and definition of the core group in the proven and young algorithm for single-step GBLUP
Authors: Abdollahi-Arpanahi Rostam , Lourenco Daniela , Misztal Ignacy
Published: May 2022

Background

The algorithm for proven and young (APY) has been suggested as a solution for recursively computing a sparse representation for the inverse of a large genomic relationship matrix (G). In APY, a subset of genotyped individuals is used as the core and the remaining genotyped individuals are used as noncore. Size and definition of the core are relevant research subjects for the application of APY, especially given the ever-increasing number of genotyped individuals.

Methods

The aim of this study was to investigate several core definitions, including the most popular animals (MPA) (i.e., animals with high contributions to the genetic pool), the least popular males (LPM), the least popular females (LPF), a random set (Rnd), animals evenly distributed across genealogical paths (Ped), unrelated individuals (Unrel), or based on within-family selection (Fam), or on decomposition of the gene content matrix (QR). Each definition was evaluated for six core sizes based on prediction accuracy of single-step genomic best linear unbiased prediction (ssGBLUP) with APY. Prediction accuracy of ssGBLUP with the full inverse of G was used as the baseline. The dataset consisted of 357k pedigreed Duroc pigs with 111k pigs with genotypes and ~ 220k phenotypic records.

Results

When the core size was equal to the number of largest eigenvalues explaining 50% of the variation of G (n = 160), MPA and Ped core definitions delivered the highest average prediction accuracies (~ 0.41−0.53). As the core size increased to the number of eigenvalues explaining 99% of the variation in G (n = 7320), prediction accuracy was nearly identical for all core types and correlations with genomic estimated breeding values (GEBV) from ssGBLUP with the full inversion of G were greater than 0.99 for all core definitions. Cores that represent all generations, such as Rnd, Ped, Fam, and Unrel, were grouped together in the hierarchical clustering of GEBV.

Conclusions

For small core sizes, the definition of the core matters; however, as the size of the core reaches an optimal value equal to the number of largest eigenvalues explaining 99% of the variation of G, the definition of the core becomes arbitrary.
StaRTrEK:in silico estimation of RNA half-lives from genome-wide time-course experiments without transcriptional inhibition
Authors: Conte Federica , Papa Federico , Paci Paola , Farina Lorenzo
Published: May 2022

Background

Gene expression is the result of the balance between transcription and degradation. Recent experimental findings have shown fine and specific regulation of RNA degradation and the presence of various molecular machinery purposely devoted to this task, such as RNA binding proteins, non-coding RNAs, etc. A biological process can be studied by measuring time-courses of RNA abundance in response of internal and/or external stimuli, using recent technologies, such as the microarrays or the Next Generation Sequencing devices. Unfortunately, the picture provided by looking only at the transcriptome abundance may not gain insight into its dynamic regulation. By contrast, independent simultaneous measurement of RNA expression and half-lives could provide such valuable additional insight. A computational approach to the estimation of RNAs half-lives from RNA expression time profiles data, can be a low-cost alternative to its experimental measurement which may be also affected by various artifacts.

Results

Here we present a computational methodology, called StaRTrEK (STAbility Rates ThRough Expression Kinetics), able to estimate half-life values basing only on genome-wide gene expression time series without transcriptional inhibition. The StaRTrEK algorithm makes use of a simple first order kinetic model and of a$$l_1$$l1-norm regularized least square optimization approach to find its parameter values. Estimates provided by StaRTrEK are validated using simulated data and three independent experimental datasets of two short (6 samples) and one long (48 samples) time-courses.

Conclusions

We believe that our algorithm can be used as a fast valuable computational complement to time-course experimental gene expression studies by adding a relevant kinetic property, i.e. the RNA half-life, with a strong biological interpretation, thus providing a dynamic picture of what is going in a cell during the biological process under study.
Associations between occupational balance, subjective health, and well-being of informal caregivers of older persons based on a cross-sectional study
Authors: Röschel Anna , Wagner Christina , Dür Mona
Published: May 2022

Objectives

Population ageing leads to a noticeable increase in demand for informal care. Informal caregivers experience high caregiver burden, such as restricted subjective health and well-being. Occupational balance is associated with subjective health and well-being. However, associations between occupational balance and subjective health and well-being of informal caregivers of older persons have not been investigated yet. Thus, the objective of this study was to explore associations between occupational balance and subjective health and well-being of informal caregivers of older persons.

Methods

From September 2016 to July 2020, a cross-sectional multicenter study design was employed in Austria. Informal caregivers’ occupational balance, subjective health, and well-being as well as comorbidity of persons to be cared for were assessed with seven self-reported questionnaires. Spearman’s rank correlation coefficients rs were calculated to determine associations between occupational balance and subjective health and well-being of informal caregivers of older persons.

Results

In total 118 informal caregivers, 102 (86%) female, and their persons to be cared for, 70 (59%) female, were considered for analyses. Median age was 58 years for informal caregivers and 81 years for persons to be cared for. Informal caregivers reported restrictions in occupational balance, subjective health, and well-being. Persons to be cared for showed comorbid health conditions. Significant associations between occupational balance and determinants of subjective health and well-being were identified (rs − 0.30 – 0.69; p ≤ 0.01).

Conclusions

As population ageing and the demand for informal care progress, efforts to support informal caregivers and to strengthen their occupational balance, subjective health and well-being are vital.
Transmission routes of antibiotic resistant bacteria: a systematic review
Authors: Godijk Noortje G. , Bootsma Martin C. J. , Bonten Marc J. M.
Published: May 2022

Background

Quantification of acquisition routes of antibiotic resistant bacteria (ARB) is pivotal for understanding transmission dynamics and designing cost-effective interventions. Different methods have been used to quantify the importance of transmission routes, such as relative risks, odds ratios (OR), genomic comparisons and basic reproduction numbers. We systematically reviewed reported estimates on acquisition routes’ contributions of ARB in humans, animals, water and the environment and assessed the methods used to quantify the importance of transmission routes.

Methods

PubMed and EMBASE were searched, resulting in 6054 articles published up until January 1st, 2019. Full text screening was performed on 525 articles and 277 are included.

Results

We extracted 718 estimates with S. aureus (n = 273), E. coli (n = 157) and Enterobacteriaceae (n = 99) being studied most frequently. Most estimates were derived from statistical methods (n = 560), mainly expressed as risks (n = 246) and ORs (n = 239), followed by genetic comparisons (n = 85), modelling (n = 62) and dosage of ARB ingested (n = 17). Transmission routes analysed most frequently were occupational exposure (n = 157), travelling (n = 110) and contacts with carriers (n = 83). Studies were mostly performed in the United States (n = 142), the Netherlands (n = 87) and Germany (n = 60). Comparison of methods was not possible as studies using different methods to estimate the same route were lacking. Due to study heterogeneity not all estimates by the same method could be pooled.

Conclusion

Despite an abundance of published data the relative importance of transmission routes of ARB has not been accurately quantified. Links between exposure and acquisition are often present, but the frequency of exposure is missing, which disables estimation of transmission routes’ importance. To create effective policies reducing ARB, estimates of transmission should be weighed by the frequency of exposure occurrence.
Weight gain rate in the second and third trimesters and fetal growth in women with gestational diabetes mellitus: a retrospective cohort study
Authors: Hong Miao , Liang Feng , Zheng Zheng , Chen Huimin , Guo Yi , Li Kuanrong , Liu Xihong
Published: May 2022

Background

Controversial evidence regarding the applicability of the IOM’s gestational weight gain (GWG) targets for women with gestational diabetes mellitus (GDM) has been reported. However, little is known about the weight gain rate (WGR) during the second and third trimesters. Moreover, previous studies failed to assess the effect modification of pre-pregnancy BMI because of the limited sample size. Therefore, we aimed to assess the applicability of the IOM recommendation for the WGR in women with GDM in different pre-pregnancy BMI categories.

Methods

We conducted this retrospective cohort study of 5275 women with GDM who delivered at Guangzhou Women and Children’s Medical Center (GWCMC) between January 2017 and January 2021. Demographic and clinical information was collected from the electronic medical record system. The primary exposure was the WGR in the late second and third trimesters; they were classified as below, within, and above the IOM standard. The outcomes were fetal growth indicators, including large-for-gestational-age (LGA), macrosomia, small-for-gestational-age (SGA), and low birth weight (LBW). The associations between the WGR and such outcomes were assessed using multiple logistic regression.

Results

A WGR below the IOM standard was associated with the decreased odds of LGA (adjusted OR 0.74; 95% CI 0.49–1.13) and macrosomia (adjusted OR 0.54, 95% CI 0.32–0.92) for women with GDM in the normal weight BMI class. Such decreases were observed greater for women with GDM in the overweight/obese class, with adjusted ORs of 0.34 (95% CI 0.09–0.88) for LGA and 0.31 (95% CI 0.01–0.84) for macrosomia, respectively. No significant difference was observed in the odds ratios of SGA and LBW across the different WGR groups.

Conclusion

LGA and macrosomia are the main outcomes associated with the WGR in the late second and third trimesters, and a WGR below the IOM standard was associated with a decreased odds of such outcomes compared with a WGR within the IOM standard in women with GDM in the normal weight and overweight/obese classes. Our findings suggest that a stricter WGR target than that of the current IOM standard may be more beneficial for women with GDM.
Overexpressed p-S6 associates with lymph node metastasis and predicts poor prognosis in non-small cell lung cancer
Authors: Tang Yaoxiang , Luo Jiadi , Zhou Ying , Zang Hongjing , Yang Yang , Liu Sile , Zheng Hongmei , Ma Jian , Fan Songqing , Wen Qiuyuan
Published: May 2022

Background

Ribosomal protein S6 (S6), a downstream effect media of the AKT/mTOR pathway, not only is a part of 40S small subunit of eukaryotic ribosome, but also involves in protein synthesis and cell proliferation during cancer development.

Methods

In present study, we explore the association between phosphorylated S6 (p-S6) protein expression and clinicopathological features as well as prognostic implications in NSCLC. P-S6 was detected in tissue microarrays (TMAs) containing 350 NSCLC, 53 non-cancerous lung tissues (Non-CLT), and 88 cases of matched metastatic lymph node lesions via immunohistochemistry (IHC). Transwell assays and wound healing assay were used to assess the effects of p-S6 inhibition on NSCLC cell metastasis.

Results

The p-S6 expression in NSCLC was more evident than that in Non-CLT (p < 0.05). Compared to NSCLC patients who have no lymph node metastasis (LNM), those with LNM had higher p-S6 expression (p = 0.001). Regardless of lung squamous cell carcinoma (SCC) or adenocarcinoma (ADC), p-S6 was increased obviously in metastatic lymph nodes compared with matched primary cancers (p = 0.001, p = 0.022, respectively). Inhibition of p-S6 decreased the metastasis ability of NSCLC cells. In addition, p-S6 was an independent predicted marker for LNM in patients with NSCLC (p < 0.001). According to survival analysis, patients with highly expressed p-S6 had a lower survival rate compared with that with lower expression (p = 0.013). P-S6 is an unfavorable independent prognostic factor for NSCLC patients (p = 0.011).

Conclusion

Increased expression of p-S6 is not only a novel predictive biomarker of LNM but also poor prognosis in NSCLC.
Computer-controlled Intraligamentary local anaesthesia in extraction of mandibular primary molars: randomised controlled clinical trial
Authors: Helmy Rodaina H. , Zeitoun Sarah I. , El-Habashy Laila M.
Published: May 2022

Background

Local anesthesia (LA) poses a threat in children more than the treatment process itself, so pediatric dentists are always demanding less painful techniques. Computer-controlled Intraligamentary anaesthesia (CC-ILA) is designed to reduce injection pain and side effects of conventional techniques. The present study aims to assess the pain experience using Computer-controlled Intraligamentary anaesthesia (CC-ILA) during injection and its effectiveness in controlling pain during extraction of mandibular primary molars in pediatric patients.

Methods

This randomized controlled clinical trial includes 50 healthy cooperative children, aged 5–7 years with mandibular primary molars indicated for extraction. They were randomly allocated to two groups according to LA technique: test group received CC-ILA and control group received Inferior alveolar nerve block (IANB). Pain was measured during injection and extraction: physiologically using Heart rate (HR), subjectively using Face-Pain-Scale (FPS), and objectively using Sound-Eye-Motor scale (SEM). Patients were recalled after 24-h to record lip-biting events. Data was collected and statistically analysed.

Results

A total of 50 children (29 females and 21 males) with mean age 6.10 ± 0.76 participated in the study. There were significantly lower scores in the heart rate in the CC-ILA group during injection (p = 0.04), but no significant difference was recorded between the two groups during extraction (p = 0.17). The SEM and FPS showed significant lower scores in the CC-ILA group during injection (p < 0.0001,p < 0.0001) and extraction (p < 0.0001,p = 0.01) respectively. No children in CC-ILA group reported lip-biting after 24-h compared to 32% in IANB (p < 0.0001).

Conclusion

CC-ILA provides significantly less painful injections than conventional techniques and has proved to be as effective as IANB during extraction of mandibular primary molars. An important advantage of this technique was the complete absence of any lip/cheek biting events.

Trial registrationThe study was prospectively registered in ClinicalTrials.gov with the identifier: NCT04739735 on 26th of January 2021,https://clinicaltrials.gov/ct2/show/NCT04739735.
The impact of death and dying on the personhood of senior nurses at the National Cancer Centre Singapore (NCCS): a qualitative study
Authors: Ho Chong Yao , Lim Nicole-Ann , Ong Yun Ting , Lee Alexia Sze Inn , Chiam Min , Gek Gillian Phua Li , Sarraf-Yazdi Shiva , Mason Stephen , Krishna Lalit
Published: May 2022

Background

A nurse’s role in caring for the dying is fraught with ethical, professional, and psychosocial challenges that impact how they perceive their roles as professionals. When unsupported, nurses caring for the dying experience burnout, career dissatisfaction and leave the profession. Better understanding of how caring for the dying affects the professional identity formation (PIF) of nurses will guide efforts to better support nurses.

Methods

Guided by new data on the subject, we adopt the theoretical lens of the Ring Theory of Personhood (RToP) to evaluate how caring for the dying impacts the values, beliefs, principles, professional identities and personhood of nurses. We employ Krishna’s Systematic Evidence-Based Approach (SEBA) to guide the design and piloting of the semi-structured interview tool.

Results

Analysis of interviews with eight senior nurses in Supportive, Palliative and Oncology care revealed three domains: Identity 1) Formation; 2) Conflict and 3) Refinement. Identity Formation occurs early in a nurse’s career, upon entering a new specialist field, and at the start of Supportive, Palliative and Oncology care. Identity Formation reveals significant changes to how self-concepts of professional identities are tied to individual concepts of personhood. Caring for the dying, however, resulted in Conflicts between values, beliefs, and principles within regnant concepts of personhood and their professional duties. These conflicts are captured as conflicts within (‘disharmony’) and/or between (‘dyssynchrony’) the rings of the RToP. These conflicts can result in changes to self-concepts of personhood and professional identities. Identity Refinement sees experience and timely support helping nurses attenuate the impact of difficult experiences. This reduces the risk of burnout and mitigates changes to their professional identities. Identity Refinement helps them develop a ‘rooted identity’ which remains relatively consistent in the face of adversity.

Conclusions

Ongoing Identity Construction amongst nurses, particularly in caring for the dying, underscore the host organisation’s role in ensuring structured, longitudinal, accessible, and personalised assessments and support of nurses, especially when they are prone to dyssynchrony and disharmony whilst caring for the terminally ill. Further study into assessment methods and the role of the environment is critical.
Use of a gamified website to increase pain neurophysiology knowledge and improve satisfaction and motivation among students studying for a degree in physiotherapy: a quasi-experimental study
Authors: Valenzuela-Pascual Fran , Pàmies-Fabra Judith , García-Martínez Ester , Martínez-Navarro Oriol , Climent-Sanz Carolina , Gea-Sánchez Montserrat , Virgili-Gomà Jordi , Rubí-Carnacea Francesc , Garcia-Escudero Maria , Blanco-Blanco Joan
Published: May 2022

Background

The scientific evidence highlights the difficulties that healthcare professionals experience when managing patients with chronic pain. One of the causes of this difficulty could be related to the acquired training and the lack of knowledge about the neurophysiology of pain. In the present study, we assessed the effectiveness of a gamified web platform in acquiring knowledge about pain neurophysiology and determining the satisfaction and motivation of students of the Degree in Physiotherapy at the University of Lleida.

Methods

A quasi-experimental study was carried out with a sample of 60 students who had access to a gamified web platform that included notes, videos, and clinical cases prepared by the teaching staff and was based on a previous study that included patients and healthcare professionals.

Results

The results show that after the intervention, there was a statistically significant increase in knowledge about the neurophysiology of pain, and the effect size was in the desired area of ​​effect. Likewise, many students considered that their motivation had increased as a result of the methodology used in the present study.

Conclusions

The results support the use of this methodology to promote knowledge about the neurophysiology of pain while improving students’ motivation.
Physicians’ knowledge and sepsis guide implementation in tertiary care hospitals in China
Authors: Han Silu , Cui Lijian , Qu Yifan , Tian Tian , Wei Bing , Wang Junyu , Yang Jun
Published: May 2022

Background

This study was designed to investigate the extent to which physicians involved in sepsis management understand and adopt sepsis guidelines in clinical practice. The overarching aim of this study was to generate ideas for developing more effective training methods to help physicians apply the guidelines in patient management.

Methods

Physicians working in a tertiary care hospital, primarily in the emergency and critical care departments, were recruited into the survey. They were asked to fill questionnaires which were designed to collect sepsis score, diagnostic indicators, fluid resuscitation, antibiotics choice, access to knowledge and training, as well as implementation of sepsis guidelines in clinical diagnosis and treatment.

Results

Overall, the response rate was 625/661 (94.5%). The investigate shows the basic information of all physicians who participated in the answer sheet, including their work department, professional title and whether their hospital was a teaching hospital. Significant differences were identified among the physicians in terms of method of acquiring sepsis guidelines, the impact of study guidelines on clinical diagnosis and treatment, efficiency of training methods, cognition of fluid resuscitation in patients with sepsis, the cognition of sepsis rehydration principles, selection of antibiotics for patients with sepsis, the basis for antibiotic selection, among other variables.

Conclusion

Although majority of physicians involved in tertiary care hospital understand the contents of sepsis-3 guidelines, the clinical implementation of the guidelines in the diagnosis and treatment of patients with sepsis is highly heterogeneous. Thus, there is need to develop standardized training for physicians involved in sepsis diagnosis and treatment.
Data-sharing and re-analysis for main studies assessed by the European Medicines Agency—a cross-sectional study on European Public Assessment Reports
Authors: Siebert Maximilian , Gaba Jeanne , Renault Alain , Laviolle Bruno , Locher Clara , Moher David , Naudet Florian
Published: May 2022

Background

Transparency and reproducibility are expected to be normative practices in clinical trials used for decision-making on marketing authorisations for new medicines. This registered report introduces a cross-sectional study aiming to assess inferential reproducibility for main trials assessed by the European Medicines Agency.

Methods

Two researchers independently identified all studies on new medicines, biosimilars and orphan medicines given approval by the European Commission between January 2017 and December 2019, categorised as ‘main studies’ in the European Public Assessment Reports (EPARs). Sixty-two of these studies were randomly sampled. One researcher retrieved the individual patient data (IPD) for these studies and prepared a dossier for each study, containing the IPD, the protocol and information on the conduct of the study. A second researcher who had no access to study reports used the dossier to run an independent re-analysis of each trial. All results of these re-analyses were reported in terms of each study’s conclusions, p-values, effect sizes and changes from the initial protocol. A team of two researchers not involved in the re-analysis compared results of the re-analyses with published results of the trial.

Results

Two hundred ninety-two main studies in 173 EPARs were identified. Among the 62 studies randomly sampled, we received IPD for 10 trials. The median number of days between data request and data receipt was 253 [interquartile range 182–469]. For these ten trials, we identified 23 distinct primary outcomes for which the conclusions were reproduced in all re-analyses. Therefore, 10/62 trials (16% [95% confidence interval 8% to 28%]) were reproduced, as the 52 studies without available data were considered non-reproducible. There was no change from the original study protocol regarding the primary outcome in any of these ten studies. Spin was observed in the report of one study.

Conclusions

Despite their results supporting decisions that affect millions of people’s health across the European Union, most main studies used in EPARs lack transparency and their results are not reproducible for external researchers. Re-analyses of the few trials with available data showed very good inferential reproducibility.

Trial registration

https://osf.io/mcw3t/
Prevalence of extended-spectrum β-lactamase-producing Enterobacterales in retail sheep meat from Zagazig city, Egypt
Authors: Abdallah H. M. , Al Naiemi N. , Elsohaby Ibrahim , Mahmoud Abdallah F. A. , Salem Gamal A. , Vandenbroucke-Grauls C. M. J. E.
Published: May 2022

Background

The goal of this study was to investigate the prevalence of extended-spectrum β-lactamase production in Enterobacterales isolated from retail sheep meat in Zagazig, Egypt.

Methods

One hundred random samples of sheep meat were collected from different retail butcher shops (n = 5) in the city of Zagazig, Egypt. Bacterial isolates were identified by MALDI-TOF MS and screened for antibiotic susceptibility by disk diffusion; further genotypic characterization of β-lactamase-encoding genes was performed with Real-Time PCR. E. coli strains were phylotyped with the Clermont triplex PCR method.

Results

Of the total of 101 bacterial isolates recovered from retail sheep meat samples, 93 were E. coli, six were Enterobacter cloacae and two were Proteus mirabilis. As many as 17% of these 100 samples showed ESBL phenotypes, all were E. coli. The blaCTX-M genes were detected in seven isolates (six were blaCTX-M-15 and one was blaCTX-M-14), three isolates harboured blaTEM (all were blaTEM-one), and two carried genes of the blaSHV family (both were blaSHV-12). Eight E. coli isolates expressed ESBL phenotype but no blaTEM, blaSHV or blaCTX-M genes were detected by PCR. ESBL- positive E. coli isolates were nearly equally distributed over the commensal groups A/B1 and the virulent group D.

Conclusion

Nearly one in five sheep meat samples was contaminated with ESBL-E. coli. This further corroborates the potential role played by contaminated meat in the increasing resistance rates that have been reported worldwide.
B7-H3 is eligible for predicting clinical outcomes in lung adenocarcinoma patients treated with EGFR tyrosine kinase inhibitors
Authors: Yang Ying , Huang Jun-feng , Hu Bing-qi , Zhou Jing , Wang Xian , Feng Zhen-zhong , Chen Yu-ting , Pan Fa-ming , Cheng Huai-dong , Chen Li-wen
Published: May 2022

Background

Not all lung adenocarcinoma (LUAD) patients with activating epidermal growth factor receptor (EGFR) mutations respond to tyrosine kinase inhibitors (TKIs) as intended. Thus, biomarkers are needed to identify patients who benefit most from EGFR-targeted therapy. Our previous in vitro data has shown that the co-signal molecule B7-H3 determines EGFR-TKI gefitinib susceptibility ofEGFR-mutated LUAD cell lines, based on the potential crosslinking between B7-H3-induced signaling and EGFR signaling.

Methods

We detected tumoral B7-H3 expression in the original biopsy from 56 treatment-naïve LUAD patients and analyzed the association between high/low B7-H3 expression with the clinical outcomes of first-line anti-EGFR therapy. The main criteria for the analysis of response were overall response rate (ORR), disease control rate (DCR), and progression-free survival (PFS), and the secondary criterion was overall survival (OS).

Results

In the subgroups of B7-H3 high and low expression, the ORR were 16.0% (4/25) and 74.2% (23/31) (p<0.001), and the DCR were 36.0% (9/25) and 87.1% (27/31) (p<0.001), respectively. The PFS of B7-H3 high [median 8.7, 95% confidence interval (CI) 4.0–13.4] was significantly worse than that of B7-H3 low (median not reached) [HR 6.54 (95% CI 2.18–19.60),p=0.001]. The median OS was 15.9 (95% CI 10.0–21.8) months in the B7-H3 high cohort and 25.7 (95% CI 9.0–42.4) months in the B7-H3 low subjects [HR 2.08 (95% CI 1.07–4.02),p=0.03], respectively. Both the univariate and multivariate analyses identified B7-H3 as an independent factor associated with poor PFS (p=0.001,p=0.000) and OS (p=0.03,p=0.015).

Conclusion

B7-H3 may serve as a potential biomarker to predict clinical outcomes inEGFR-mutated LUAD patients treated with first-line EGFR-TKIs.
Long noncoding RNAs as regulators of pediatric acute myeloid leukemia
Authors: Neyazi Sina , Ng Michelle , Heckl Dirk , Klusmann Jan-Henning
Published: May 2022

Long noncoding RNAs (lncRNAs) are increasingly emerging as regulators across human development and disease, and many have been described in the context of hematopoiesis and leukemogenesis. These studies have yielded new molecular insights into the contribution of lncRNAs to AML development and revealed connections between lncRNA expression and clinical parameters in AML patients. In this mini review, we illustrate the versatile functions of lncRNAs in AML, with a focus on pediatric AML, and present examples that may serve as future therapeutic targets or predictive factors.
Relationship between smoking, narcissism, and impulsiveness among young women
Authors: Kertzman Semion , Kagan Alex , Vainder Michael , Lapidus Rina , Weizman Abraham
Published: May 2022

Although the connection between smoking and individual differences has been recently recognized, the relationship between narcissistic personality traits and cigarette smoking has received less attention. The notion that personality traits can be associated with addictive behavior is influential in clinical practice. However, questions remain about specific interactions between smoking and personality characteristics that need empirical support to substantiate this hypothesis. This study thus identifies narcissistic and impulsive personality traits as precursors of smoking in a sample of tattooed individuals. In a cross-sectional study (N = 120), personality traits were assessed in young women (aged 18–35 years) using the narcissistic personality inventory and the Barratt Impulsivity Scale (BIS-11). The current study, using the regression analysis, has clearly demonstrated that young women who smoke have different personality characteristics as compared with women who do not smoke.
Fibrin monomer complex on postoperative day 1 is correlated with the volume of deep vein thrombosis after knee surgery
Authors: Akagawa Manabu , Kijima Hiroaki , Kimura Yoshiaki , Saito Hidetomo , Saito Kimio , Wakabayashi Ikuko , Kashiwagura Takeshi , Miyakoshi Naohisa
Published: May 2022

Purpose

Patients undergoing knee surgery are at high risk for deep vein thrombosis (DVT), which is infrequent but potentially life-threatening. It has not been identified how to efficiently detect high-risk DVT while minimizing bleeding complications from anticoagulation. We hypothesized that the degree of activation of thrombotic markers may correlate with the size of the thrombus. Therefore, we investigated the correlation between thrombotic markers and DVT thrombus volume in patients after knee surgery.

Methods

This retrospective study involved 29 patients who underwent around knee osteotomy or total / unicompartmental knee arthroplasty from 2018 to 2020. Fibrin monomer complex (FMC) at 1, and 7 days after surgery, and D-dimer at 4, and 7 days after surgery were investigated. In addition, the volume of DVT was estimated with ultrasonography at the 7 days after surgery. Body mass index, surgical time, and total volume of blood loss were also evaluated. Factors related to thrombus volume were examined statistically.

Results

Nine patients (31.0%) exhibited asymptomatic distal DVT, whereas 1 patient (3.4%) experienced asymptomatic proximal DVT. No patients had pulmonary embolism. Statistical analysis showed that only FMC concentration on postoperative day 1 was significantly correlated with thrombus volume (p <  0.001, 95% confidence interval 0.41 to 0.839, r = 0.679).

Conclusions

The FMC concentration was a useful early indicator of deep vein thrombosis after knee surgery. Monitoring the FMC concentration could enable selective identification of patients with a high thrombus volume, which is associated with a high risk for pulmonary embolism.
Prognostic value of cervical nodal necrosis on staging imaging of nasopharyngeal carcinoma in era of intensity-modulated radiotherapy: a systematic review and meta-analysis
Authors: Ai Qi-Yong H. , Hung Kuo Feng , So Tiffany Y. , Mo Frankie K. F. , Tsung Anthony Chin Wing , Hui Edwin P. , Ma Brigette B. Y. , Ying Michael , King Ann D.
Published: May 2022

Purposes

To systematically review and perform meta-analysis to evaluate the prognostic value of cervical nodal necrosis (CNN) on the staging computed tomography/magnetic resonance imaging (MRI) of nasopharyngeal carcinoma (NPC) in era of intensity-modulated radiotherapy.

Methods

Literature search through PubMed, EMBASE, and Cochrane Library was conducted. The hazard ratios (HRs) with 95% confidence intervals (CIs) of CNN for distant metastasis-free survival (DMFS), disease free survival (DFS) and overall survival (OS) were extracted from the eligible studies and meta-analysis was performed to evaluate the pooled HRs with 95%CI.

Results

Nine studies, which investigated the prognostic values of 6 CNN patterns on MRI were included. Six/9 studies were eligible for meta-analysis, which investigated the CNN presence/absence in any nodal group among 4359 patients. The pooled unadjusted HRs showed that the CNN presence predicted poor DMFS (HR =1.89, 95%CI =1.72-2.08), DFS (HR =1.57, 95%CI =1.08-2.26), and OS (HR =1.87, 95%CI =1.69-2.06). The pooled adjusted HRs also showed the consistent results for DMFS (HR =1.34, 95%CI =1.17-1.54), DFS (HR =1.30, 95%CI =1.08-1.56), and OS (HR =1.61, 95%CI =1.27-2.04). Results shown in the other studies analysing different CNN patterns indicated the high grade of CNN predicted poor outcome, but meta-analysis was unable to perform because of the heterogeneity of the analysed CNN patterns.

Conclusion

The CNN observed on the staging MRI is a negative factor for NPC outcome, suggesting that the inclusion of CNN is important in the future survival analysis. However, whether and how should CNN be included in the staging system warrant further evaluation.
Patients with hemodialysis-induced hypoxemia had a poor prognosis of COVID-19
Authors: Toda Masataro , Yoshifuji Ayumi , Fujii Kentaro , Komatsu Motoaki , Kato Ai , Tamura Ikue , Sugi Wataru , Ryuzaki Munekazu
Published: May 2022

Background

We experienced that some hemodialysis (HD) patients with coronavirus disease 2019 (COVID-19) exacerbated hypoxemia during HD. Though HD-induced hypoxemia has been reported, there have been no reports of HD-induced hypoxemia in patients with COVID-19 and its effect on prognosis of COVID-19.

Methods

Eleven HD patients admitted with COVID-19 from August 2020 to April 2021 were classified into the patients whose oxygen demand increased by more than 3 L/min with mask during HD (worsened group, n = 5) and others (not-worsened group, n = 6). The background, laboratory findings, severity of COVID-19 and prognosis were compared between the two groups. In addition, blood gases were measured before and after dialysis among HD patients admitted with COVID-19 on April 2021 (n = 3).

Results

There were no significant differences in backgrounds, except for a higher proportion of diabetes mellitus in worsened group (p = 0.04). Although laboratory findings were not significantly different on admission day, albumin and LDH levels 7 days after admission were significantly lower and higher in worsened group, respectively (p = 0.03 and < 0.01). The severity of COVID-19 and survival rate were significantly worse in worsened group (p = 0.01 and 0.03). The alveolar-arterial oxygen pressure difference (Aa-DO2) opened during HD in a patient with HD-induced hypoxemia, but did not open in patients without HD-induced hypoxemia.

Conclusions

There is a close relationship among HD-induced hypoxemia and poor prognosis of COVID-19. The HD-induced hypoxemia of patients with COVID-19 may be caused by ventilation/perfusion mismatching.
Repeated streptococcal peritoneal dialysis-related peritonitis following stomatitis and gingival bleeding: a case report
Authors: Fukumitsu Kento , Oka Hideaki , Iwamoto Takaki , Kondo Mika , Hirashima Yutaro , Kamimura Taro , Nakano Toshiaki , Kitazono Takanari
Published: May 2022

Background

Identification of the pathogenesis of peritoneal dialysis (PD)-related peritonitis is important. However, identification of endogenous peritonitis, especially hematogenous infection, is difficult, and there are few reports of endogenous peritonitis via the bloodstream. We report a case of PD-related peritonitis presumed to be caused by hematogenous infection through the oral mucosa.

Case presentation

A 65-year-old woman commenced PD at the age of 52. Over the next 13 years, she developed two episodes of streptococcal peritonitis caused by Streptococcus salivarius, a commensal bacteria of the human oral mucosa, and all episodes occurred following stomatitis and gingival bleeding in the early summer. At the age of 65, she again suffered from stomatitis followed by gingival bleeding in early summer, and 2 weeks later, developed a third case of peritonitis caused by Streptococcus salivarius. The streptococcal peritonitis improved immediately following 2 weeks of antibiotic treatment. We surmise that the patient is subject to weakened immunity in the early summer, causing repeated oral problems with gingival bleeding, and subsequently leading to oral streptococcal peritonitis.

Conclusions

Our findings suggest that oral streptococcal peritonitis following oral problems such as stomatitis and gingival bleeding results from a hematogenous infection via the oral mucosa.
Factors affecting mechanical thrombectomy outcome in acute ischemic stroke patients: an Egyptian sample
Authors: Elwan Mohammed Ezzat , Mansour Ossama Yasin , Lashin Mohamed Elsaeed , Melake Mostafa Saleh
Published: May 2022

Background

Stroke constitutes a major health problem worldwide, nowadays endovascular treatment is considered to be a standard of care in acute ischemic stroke patients with large vessel occlusion, accurate prediction of outcome of thrombectomy is essential for health care providers, patients and families. We studied different clinical and radiological variables that could predict functional outcome in stroke patients after thrombectomy. Thirty-four consecutive ischemic stroke patients were included, received intravenous tissue plasminogen activator (iv-tpa), then mechanical thrombectomy was done. Patients were clinically assessed at admission with National Institute of Health Stroke Scale (NIHSS) then evaluated by the Alberta Stroke Program early computerized tomography (CT) score (ASPECTS), clot burden scale (CBS) and collateral score (CS) in multiphase computerized tomography angiography (CTA) then good and poor outcomes at 3 months were defined by Modified Rankin Scale (MRS) of 0–2 and 3–6 points, respectively.

Results

Factors associated with good outcome (MRS 0–2) were lower admission NIHSS score (p < 0.037), small infarct core aspects ≥ 6 (p < 0.001), low clot burden (CBS 7–10) (p = 0.046) good collaterals (2–3) (p = 0.038) and absence of post-procedure hemorrhage (p < 0.0005).

Conclusions

Low admission NIHSS score, absence of post-procedure hemorrhage, small infarct core, low clot burden and good collaterals are reliable factors for good clinical outcome.
Revising the Treatment Pathways in Lymphoma: New Standards of Care—How Do We Choose?
Authors: Ngu Henry , Takiar Radhika , Phillips Tycel , Okosun Jessica , Sehn Laurie H.
Published: May 2022

Diffuse large B-cell lymphoma and follicular lymphoma are the most commonly encountered non-Hodgkin lymphomas in clinical practice. Both are biologically heterogeneous, with management strategies that are becoming increasingly complex. Diffuse large B-cell lymphoma typically exhibits aggressive behavior but can be cured in the majority of cases with immunochemotherapy. While R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) has been the standard of care for decades, the recent combination of polatuzumab-vedotin-R-CHP (rituximab plus cyclophosphamide, doxorubicin, and prednisone) has demonstrated improved progression-free survival for patients with intermediate- and intermediate-high–risk disease. Numerous novel therapies, including targeted agents and immunotherapy-based approaches, have recently been approved for relapsed/refractory disease and have led to improved outcomes. Follicular lymphoma is an indolent lymphoma that remains incurable with standard approaches. Overall survival in most patients is excellent, although a proportion of patients will have early relapsing disease and poorer outcomes. The availability of novel agents in the relapsed/refractory setting has shifted the treatment algorithm, which requires thoughtful consideration of sequencing. This article will review recent developments in the treatment of diffuse large B-cell lymphoma and relapsed/refractory follicular lymphoma.
Novel Therapies in Gynecologic Cancer
Authors: Bejar Francisco Grau , Oaknin Ana , Williamson Casey , Mayadev Jyoti , Peters Pamela N. , Secord Angeles Alvarez , Wield Alyssa M. , Coffman Lan G.
Published: May 2022

During the past decade, considerable strides have been made in the understanding and treatment of gynecologic cancers. The advent of PARP inhibitors, antiangiogenic therapies, immunotherapy combinations, and targeted agents have altered the standard of care in ovarian, endometrial, and cervical cancers. However, continued advancement in the treatment of gynecologic cancers is critical. Fortunately, exciting work defining new therapeutic targets and novel treatment strategies is on the horizon. Here, we discuss emerging treatments for gynecologic cancers, including endometrial, cervical, ovarian, and rare gynecologic cancers. We highlight research that has deepened our understanding of the unique biology and molecular underpinnings of these cancers and is being translated into powerful new treatment approaches. We particularly highlight the advent of immunotherapy in endometrial cancer; radiosensitizers in cervical, vaginal, and vulvar cancers; targeted therapies in ovarian cancer; and molecularly driven approaches to treat rare gynecologic cancers. Continued basic, translational, and clinical research holds the promise to change the landscape of gynecologic cancer and improve the lives of all women impacted by these diseases.
Model of hydrophobic porous media applied to stratified media: Water trapping, intermittent flow and fingering instability
Authors: Beltrame P. , Cajot F.
Published: May 2022

A macroscopic model of water infiltration is developed and applied to a stratified porous medium containing hydrophilic and hydrophobic layers. The governing equation is a gradient dynamics as in the Richards model but in which a wettability term replaces the suction pressure, taking into account the effective action of the hydrophobic matter. The resulting governing equation is a fourth-order PDE similar to the lubrication model or Cahn-Hilliard equations known to reproduce complex dynamics such as intermittency and fingering instability. The model makes it possible to simulate the finite spreading of water in horizontal directions when the porous medium is hydrophobic. Applied to a stratified medium alternating hydrophilic and hydrophobic layers, we highlight, depending on the mean water content, phenomena of water trapping in hydrophilic layers, intermittent flow and fingering instability. These regimes are studied using time integration bifurcation and numerical continuation tools.
Alignment of the cell long axis by unidirectional tension acts cooperatively with Wnt signalling to establish planar cell polarity
Authors: Hirano Sayuki , Mii Yusuke , Charras Guillaume , Michiue Tatsuo
Published: May 2022

Planar cell polarity (PCP) is the aligned cell polarity within a tissue plane. Mechanical signals are known to act as a global cue for PCP, yet their exact role is still unclear. In this study, we focused on PCP in the posterior neuroectoderm of Xenopus laevis and investigated how mechanical signals regulate polarity. We reveal that the neuroectoderm is under a greater tension in the anterior-posterior direction and that perturbation of this tension causes PCP disappearance. We show that application of uniaxial stretch to explant tissues can control the orientation of PCP and that cells sense the tissue stretch indirectly through a change in their shape, rather than directly through detection of anisotropic tension. Furthermore, we reveal that PCP is most strongly established when the orientation of tissue stretch coincides with that of diffusion of locally expressed Wnt ligands, suggesting a cooperative relationship between these two PCP regulators.