bluuebunny/crossref_metadata_2025 huggingface dataset:
Real-time evaluation of the independent analgesic efficacy of dexmedetomidine
Authors: Wang XiaoHua , Zhang SiYuan , Wang Chunxiu , Huang Yi , Wu Hao , Zhao Guoguang , Wang TianLong
Published: March 2023

Background

Dexmedetomidine has analgesic properties, but the intraoperative analgesic effect of dexmedetomidine is often masked by the effects of other general anaesthetics. Therefore, the degree to which it reduces intraoperative pain intensity remains unclear. The objective of this double-blind, randomised controlled trial was to evaluate the independent intraoperative analgesic efficacy of dexmedetomidine in real-time.

Methods

This single-centre study enrolled 181 patients who were hospitalised for below-knee orthopaedic surgeries between 19 January 2021 to 3 August 2021 were eligible for this is single-centre study. Peripheral neural block was performed on patients scheduled for below-knee orthopaedic surgeries. Patients were randomly assigned to the dexmedetomidine or midazolam group and were intravenously administered with 1.5 µg kg−1 h−1dexmedetomidine or 50 µg kg−1 h−1midazolam, respectively. The analgesic efficacy was evaluated using the real-time non-invasive nociception monitoring. The primary endpoint was the attainment rate of the nociception index target. The secondary endpoints included the occurrence of intraoperative hypoxemia, haemodynamic parameters, the consciousness index, electromyography and patient outcomes.

Results

On Kaplan–Meier survival analysis, the defined nociception index target was attained in 95.45% and 40.91% of patients receiving dexmedetomidine and midazolam, respectively. Log-rank analysis revealed that the dexmedetomidine group attained the nociception index target significantly faster and the median attainment time of the nociception index target in the dexmedetomidine group was 15 min. Dexmedetomidine group was associated with a significantly lower incidence of hypoxemia. There was no significant difference in blood pressure between the dexmedetomidine and midazolam groups. Further, the dexmedetomidine group had a lower maximum visual analogue scale score and lower analgesic consumption postoperatively.

Conclusions

Dexmedetomidine has independent analgesia and systemically administered as an adjuvant agent has better analgesic efficacy than midazolam without severe side effects.

Trial registration

clinicaltrial.gov Registry Identifier: NCT-04675372.Registered on 19/12 /2020.
Clinical trial participation predicts improved survival in older adults receiving allogeneic blood and marrow transplant
Authors: Thornton Clifton P. , Bandeen-Roche Karen , Dolinar Madeline , Roberts Lavigne Laken C. , George Lansey Dina , Jones Rick , Walston Jeremy , Varadhan Ravi , Hladek Melissa , Imus Philip
Published: March 2023

Background

Older adults represent a large oncologic demographic and are under-represented within oncology research despite constituting nearly two-thirds of the oncologic population in the United States. Because many social factors influence research participation, those who enroll in research do not reflect the oncology population at large, introducing bias and creating issue with external validity of studies. The same factors that influence study enrollment may also impact cancer outcomes, meaning that those who enroll in studies may already have an improved chance of cancer survival, further skewing results of these studies. This study evaluates characteristics that influence study enrollment in older adults and explore to what degree these factors may influence survival after allogeneic blood or marrow transplantation.

Methods

This retrospective comparison study evaluates 63 adults aged 60 and above undergoing allogenic transplantation at one institution. Patients who elected and declined enrollment in a non-therapeutic observational study were evaluated. Demographic and clinical characteristics between groups were compared and assessed as predictors of transplant survival, including decision to enroll in the study.

Results

Participants who chose to enroll in the parent study were not different with regard to gender, race/ethnicity, age, insurance type, donor age, and neighborhood income/poverty level compared to patients who were invited to participate but declined enrollment. The research participant group had higher proportion assessed as being fully active (23.8% vs. 12.7%, p = 0.034) and lower mean comorbidity scores (1.0 vs 2.47, p = 0.008). Enrollment in an observational study independently predicted transplant survival (HR = 0.316, 95% CI 0.12–0.82, p = 0.017). When controlling for relevant confounders of disease severity, comorbidities, and transplant age, enrolling in the parent study was associated with a lower hazards of death following transplant (HR = 0.302, 95% CI 0.10–0.87, p = 0.027).

Conclusions

Despite being demographically comparable, persons who enrolled in one non-therapeutic transplant study had significantly improved survivorship than those who did not participate in observational research. These findings suggest that there are unidentified factors that influence study involvement that may also impact disease survivorship, over-estimating outcomes from these studies. Results from prospective observational studies should be interpreted with the consideration that study participants have an improved chance of survival at baseline.
Stuttering as a signal of encephalopathy associated with toripalimab in a pancreatic ductal adenocarcinoma patient: a case report
Authors: He Jianping , Chen Xi , Cheng Ke , Lv Wanrui , Cao Dan , Li Zhiping
Published: March 2023

Background

Immune checkpoint inhibitor (ICI) combined with chemotherapy has exhibited promising results in small sample studies of pancreatic cancer patients. The efficacy of toripalimab, a programmed cell death protein 1 (PD-1) monoclonal antibody has been explored in the previous studies and it was established that immune-related adverse events (irAEs) associated with administration of this drug deserve proper attention and adequate management.

Case presentation

A 43-year-old female patient with advanced pancreatic ductal adenocarcinoma (PDAC) was treated with toripalimab in combination with gemcitabine and nab-paclitaxel (T-GA) as the first-line treatment. She developed immune-related encephalopathy with stuttering as the main clinical symptom and Magnetic resonance imaging (MRI) showed multiple cerebral white matter demyelination changes, concomitant with asymptomatic cardiac enzyme elevation and hypothyroidism. The symptoms resolved after the discontinuation of toripalimab and corticosteroid treatment.

Conclusions

Stuttering might be an early sign of neurotoxicity which can be easily neglected during the treatment. These findings provide guidance for the identification of these rare and occult neurological irAEs (n-irAEs) in the clinical practice.
Establishment of a single-center-based early prognostic scoring system for Guillain-Barré syndrome
Authors: Di Xiaomeng , Wang Jiawei , Li Lei , Liu Lei
Published: March 2023

Background

Previous studies have developed clinical prognostic models for Guillain-Barré syndrome including EGOS and mEGOS, they have good reliability and accuracy, but individual entries are poor. This study aims to establish a scoring system to predict the early prognosis, in order to provide additional treatment for patients with poor prognosis and shorten the length of hospital stay.

Methods

We retrospectively analyzed risk factors affecting the short-term prognosis of Guillain-Barré syndrome, and developed a scoring system for early determination of disease prognosis. Sixty two patients were divided into two groups based on the Hughes GBS disability score at discharge. Groups were compared for differences in gender, age at onset, antecedent infection, cranial nerve involvement, pulmonary infection, mechanical ventilation support, hyponatremia, hypoproteinemia, impaired fasting glucose, and peripheral blood neutrophil-to-lymphocyte ratio. Statistically significant factors were included in a multivariate logistic regression analysis, and a scoring system to predict the short-term prognosis was established based on the regression coefficients. The receiver operating characteristic curve of this scoring system was plotted, and the area under the ROC curve was calculated to assess the accuracy of the prediction model.

Results

Univariate analysis revealed that age at onset, antecedent infection, pneumonia, mechanical ventilation support, hypoalbuminemia, hyponatremia, impaired fasting glucose, and elevated peripheral blood neutrophil-to-lymphocyte ratio were risk factors for poor short-term prognosis. The above factors were included in the multivariate logistic regression analysis, and pneumonia, hypoalbuminemia, and hyponatremia could be used as independent predictors. The receiver operating characteristic curve was plotted with a calculated area under the ROC curve of 82.2% (95% CI 0.775—0.950, P < 0.0001). The best cut-off value for the model score was 2, with a sensitivity of 0.9091, a specificity of 0.7255, and a Youden index of 0.6346.

Conclusion

Pneumonia, hyponatremia, and hypoalbuminemia were independent risk factors for poorer short-term prognosis in patients with Guillain-Barré syndrome. The short-term prognosis scoring system of Guillain-Barré syndrome we constructed using these variables had some predictive value, and the short-term prognosis with quantitative scores of 2 or more was worse.
Unwinding the tangle of adolescent pregnancy and socio-economic functioning: leveraging administrative data from Manitoba, Canada
Authors: Jakubowski Aleksandra , Roos Leslie L. , Wall-Wieler Elizabeth
Published: March 2023

Background

Understanding the relationship between adolescent pregnancy and adult education and employment outcomes is complicated due to the endogeneity of fertility behaviors and socio-economic functioning. Studies exploring adolescent pregnancy have often relied on limited data to measure adolescent pregnancy (i.e. birth during adolescence or self-reports) and lack access to objective measures of school performance during childhood.

Methods

We use rich administrative data from Manitoba, Canada, to assess women’s functioning during childhood (including pre-pregnancy academic performance), fertility behaviors during adolescence (live birth, abortion, pregnancy loss, or no history of pregnancy), and adult outcomes of high school completion and receipt of income assistance. This rich set of covariates allows calculating propensity score weights to help adjust for characteristics possibly predictive of adolescent pregnancy. We also explore which risk factors are associated with the study outcomes.

Results

We assessed a cohort of 65,732 women, of whom 93.5% had no teen pregnancy, 3.8% had a live birth, 2.6% had abortion, and < 1% had a pregnancy loss. Women with a history of adolescent pregnancy were less likely to complete high school regardless of the outcome of that pregnancy. The probability of dropping out of high school was 7.5% for women with no history of adolescent pregnancy; after adjusting for individual, household, and neighborhood characteristics, the probability of dropping out of high school was 14.2 percentage points (pp) higher (95% CI 12.0-16.5) for women with live birth, 7.6 pp. higher (95% CI 1.5-13.7) for women with a pregnancy loss, and 6.9 pp. higher (95% CI 5.2-8.6) for women who had abortion. They key risk factors for never completing high school are poor or average school performance in 9th grade. Women who had a live births during adolescence were much more likely to receive income assistance than any other group in the sample. Aside from poor school performance, growing up in poor households and in poor neighborhoods were also highly predictive of receiving income assistance during adulthood.

Discussion

The administrative data used in this study enabled us to assess the relationship between adolescent pregnancy and adult outcomes after controlling for a rich set of individual-, household-, and neighborhood-level characteristics. Adolescent pregnancy was associated with higher risk of never completing high school regardless of the pregnancy outcome. Receipt of income assistance was significantly higher for women having a live birth, but only marginally higher for those who had a pregnancy that ended in loss or termination, underlining the harsh economic consequences of caring for a child as a young mother. Our data suggest that interventions targeting young women with poor or average school marks may be especially effective public policy priorities.
Association of disrespectful care after childbirth and COVID-19 exposure with postpartum depression symptoms- a longitudinal cohort study in Nepal
Authors: KC Ashish , Acharya Ankit , Bhattarai Pratiksha , Basnet Omkar , Shrestha Anisha , Rijal Garima , Skalkidou Alkistis
Published: March 2023

Background

The COVID-19 pandemic has led to unprecedented mental stress to women after childbirth. In this study, we assessed the association of disrespectful care after childbirth and COVID-19 exposure before/during labour with postpartum depression symptoms assessed at 7 and 45 days in Nepal.

Methods

A longitudinal cohort study was conducted in 9 hospitals of Nepal among 898 women. The independent data collection system was established in each hospital to collection information on disrespectful care after birth via observation, exposure to COVID-19 infection before/during labour and other socio-demographic via interview. The information on depressive symptoms at 7 and 45 days was collected using the validated Edinburg Postnatal Depression Scale (EPDS) tool. Multi-level regression was performed to assess the association of disrespectful care after birth and COVID-19 exposure with postpartum depression.

Result

In the study, 16.5% were exposed to COVID-19 before/during labour and 41.8% of them received disrespectful care after childbirth. At 7 and 45 days postpartum, 21.3% and 22.4% of women reported depressive symptoms respectively. In the multi-level analysis, at the 7th postpartum day, women who had disrespectful care and no COVID-19 exposure still had 1.78 higher odds of having depressive symptom (aOR, 1.78; 95% CI; 1.16, 2.72). In the multi-level analysis, at 45th postpartum day, women who had disrespectful care and no COVID-19 exposure had 1.37 higher odds of having depressive symptoms (aOR, 1.37; 95% CI; 0.82, 2.30), but not statistically significant.

Conclusion

Disrespectful care after childbirth was strongly associated with postpartum depression symptoms irrespective of COVID-19 exposure during pregnancy. Caregivers, even during the global pandemic, should continue to focus their attention for immediate breast feeding and skin-to-skin contact, as this might reduce the risk for depressive symptoms postpartum.
Dyslipidemia is associated with a poor prognosis of breast cancer in patients receiving neoadjuvant chemotherapy
Authors: Ma Youzhao , Lv Minhao , Yuan Peng , Chen Xiuchun , Liu Zhenzhen
Published: March 2023

Background

Lipid metabolism disorders may be involved in the occurrence and development of breast cancer. This study aimed to investigate the serum lipid changes during neoadjuvant chemotherapy for breast cancer and the effect of dyslipidemia on the prognosis of breast cancer patients.

Methods

We collected the data from 312 breast cancer patients who underwent surgery after receiving standard neoadjuvant therapy. χ2 test and T-test were employed to analyze the effect of chemotherapy on the serum lipid metabolism of patients. The effects of dyslipidemia on the disease-free survival (DFS) of patients with breast cancer were analyzed by χ2 test and COX regression analysis.

Results

A total of 56 out of 312 patients (17.9%) suffered from relapse. The baseline serum lipid level of the patients was significantly correlated with their age and body mass index (BMI) (p < 0.05). Chemotherapy increased the levels of triglycerides, total cholesterol, and low-density lipoprotein cholesterol, but decreased the level of high-density lipoprotein cholesterol (p < 0.001). Preoperative dyslipidemia was significantly associated with the axillary pCR rate (p < 0.05). COX regression analysis revealed that the full-course serum lipid level (HR = 1.896 [95%CI 1.069–3.360]; p = 0.029), N stage (HR = 4.416 [95%CI 2.348–8.308]; p < 0.001) and the total pCR rate (HR = 4.319 [95%CI 1.029–18.135]; p = 0.046) acted as prognostic factors affecting DFS in breast cancer. The relapse rate in patients with a high level of total cholesterol was higher than that in patients with a high level of triglycerides (61.9% vs 30.0%; p < 0.05).

Conclusions

Dyslipidemia deteriorated after chemotherapy. The full-course serum lipid level may thus serve as a blood marker for predicting breast cancer prognosis. Serum lipids should therefore be closely monitored in breast cancer patients throughout the treatment course, and patients with dyslipidemia should be treated in a timely manner.
A mosaic karyotype of 45,X/46,X,psu idic(Y)(q12) in a ten-year-old boy: integrating high-throughput sequencing with cytogenetic technique for precise diagnosis and genetic counselling
Authors: Yin Hui , Xie Hua , Zou Jizhen , Ye Xue , Liu Ying , He Cai , Shangguan Shaofang , Liu Haoran , Chen Xiaoli , Chen Xiaobo
Published: March 2023

Background

Isodicentric Y chromosome (idic(Y)) is the most commonly reported aberration of the human Y chromosome, which is an important cause of abnormal sexual development. The breakpoints of isodicentric Y chromosome mostly occurred in Yq11.2 and Yp11.3, however, the breakpoints in Yq12 are relatively rare.

Case presentation

We described a 10-year-old boy presenting hypospadias, micropenis and short stature, as well as unilateral cryptorchidism without normal testicular seminiferous tubules structure by biopsy. Whole exome sequencing didn’t find any pathogenic/likely pathogenic variants related to phenotypes of this patient. Copy number variation sequencing showed the duplication of whole Y chromosome. Subsequently, karyotyping and FISH analyses demonstrated his genetic diagnosis was mosaic 45,X[8]/46,X,psu idic(Y)(q12)[32], with the breakpoint in Yq12.

Conclusions

Our case proved that it would be beneficial to integrate high-throughput sequencing with cytogenetic technique for precise diagnosis, treatment and genetic counselling.
Parental experiences of live video streaming technology in neonatal care in England: a qualitative study
Authors: Gallagher Katie , Hayns-Worthington Ruby , Marlow Neil , Meek Judith , Chant Kathy
Published: March 2023

Background

The use of bedside cameras in neonatal units facilitates livestreaming of infants to support parental and family bonding when they are unable to be physically present with their baby. This study aimed to explore the experiences of parents of infants previously admitted for neonatal care and who used live video streaming to view their baby in real-time.

Methods

Qualitative semi-structured interviews were conducted after discharge with parents of infants admitted for neonatal care on a tertiary level neonatal unit in the UK in 2021. Interviews were conducted virtually, transcribed verbatim and uploaded into NVivo V12 to facilitate analysis. Thematic analysis by two independent researchers was undertaken to identify themes representing the data.

Results

Seventeen participants took part in sixteen interviews. Thematic analysis identified 8 basic themes which were grouped into 3 organizational themes: (1) family integration of the baby including parent-infant, sibling-infant, and wider family-infant attachment facilitated through livestreaming, (2) implementation of the livestreaming service including communication, initial set up of the livestreaming service, and areas for improvement, and (3) parental control including emotional, and situational control.

Conclusions

The use of livestreaming technology can provide parents with opportunities to integrate their baby into their wider family and friendship community and gain a sense of control over their baby’s admission for neonatal care. On-going parental education around how to use, and what to expect from, livestreaming technology is required to minimise any potential distress from viewing their baby online.
Molecular characterization of the circadian clock in paediatric leukaemia patients: a prospective study protocol
Authors: Ludwig Marius , Basti Alireza , Yalçin Müge , Schulte Johannes H. , Relógio Angela
Published: March 2023

Background

In many organisms, including humans, the timing of cellular processes is regulated by the circadian clock. At the molecular level the core-clock consists of transcriptional-translational-feedback loops including several genes such as BMAL1, CLOCK, PERs and CRYs generating circa 24-h rhythms in the expression of about 40% of our genes across all tissues. Previously these core-clock genes have been shown to be differentially expressed in various cancers. Albeit a significant effect in treatment optimization of chemotherapy timing in paediatric acute lymphoblastic leukaemia has previously been reported, the mechanistic role played by the molecular circadian clock in acute paediatric leukaemia remains elusive.

Methods

To characterize the circadian clock, we will recruit patients with newly diagnosed leukaemia and collect time course saliva and blood samples, as well as a single bone marrow sample. From the blood and bone marrow samples nucleated cells will be isolated and further undergo separation into CD19+ and CD19− cells. qPCR is performed on all samples targeting the core-clock genes including BMAL1, CLOCK, PER2 and CRY1. Resulting data will be analysed for circadian rhythmicity using the RAIN algorithm and harmonic regression.

Discussion

To the best of our knowledge this is the first study aiming to characterize the circadian clock in a cohort of paediatric patients with acute leukaemia. In the future we hope to contribute to uncovering further vulnerabilities of cancers associated with the molecular circadian clock and in particular adjust chemotherapy accordingly, leading to more targeted toxicity, and hence decreased systemic toxicities.
Intellectual disabilities and autism among children with congenital heart defects, Western Australia, 1983–2010
Authors: Bircan Emine , Politis Maria D. , Gokun Yevgeniya , Luo Chunqiao , Leonard Helen , Bourke Jenny , Bower Carol , Nembhard Wendy N.
Published: March 2023

Background

Children with congenital heart defects (CHDs) are at higher risk of developing an intellectual disability. However, severity of intellectual disabilities among this group of children are largely unknown. Our objective was to determine the risk of intellectual disability (ID), ID severity, and autism among children with CHDs.

Methods

We conducted a retrospective cohort study of singleton live births in Western Australia (n = 20,592) between 1983 and 2010. Children with CHDs were identified from the Western Australian Register for Developmental Anomalies (n = 6563) and infants without CHDs were randomly selected from state birth records (n = 14,029). Children diagnosed with ID before 18 years were identified by linkage to statewide Intellectual Disability Exploring Answers database. Odds ratios (OR) and 95% confidence intervals (CI) were calculated from logistic regression models for all CHDs combined and by CHD severity adjusting for potential confounders.

Results

Of 20,592 children, 466 (7.1%) with CHDs and 187 (1.3%) without CHDs had an ID. Compared to children without CHDs, children with any CHD had 5.26 times (95% CI 4.42, 6.26) the odds of having an ID and 4.76 times (95% CI 3.98, 5.70) the odds of having mild/moderate ID. Children with any CHD had 1.76 times the odds of having autism (95% CI 1.07, 2.88), and 3.27 times the odds of having an unknown cause of ID (95% CI 2.65, 4.05) compared to children without CHD. The risk of having autism (aOR 3.23, 95% CI 1.11, 9.38), and unknown cause of ID (aOR 3.45, 95% CI 2.09, 5.70) was greatest for children with mild CHD.

Conclusions

Children with CHDs were more likely to have an ID or autism. Future research should elucidate underlying etiology of ID in children with CHDs.
Thymoquinone, piperine, and sorafenib combinations attenuate liver and breast cancers progression: epigenetic and molecular docking approaches
Authors: El-Shehawy Ashraf A. , Elmetwalli Alaa , El-Far Ali H. , Mosallam Sahar Abd El-Razik , Salama Afrah Fatthi , Babalghith Ahmad O. , Mahmoud Mohammad A. , Mohany Hany , Gaber Mohamed , El-Sewedy Tarek
Published: March 2023

Background

Traditional herbal medicine has been used for centuries to cure many pathological disorders, including cancer. Thymoquinone (TQ) and piperine (PIP) are major bioactive constituents of the black seed (Nigella sativa) and black pepper (Piper nigrum), respectively. The current study aimed to explore the potential chemo-modulatory effects, mechanisms of action, molecular targets, and binding interactions after TQ and PIP treatments and their combination with sorafenib (SOR) against human triple-negative breast cancer (MDA-MB-231) and liver cancer (HepG2) cells.

Methods

We determined drug cytotoxicity by MTT assay, cell cycle, and death mechanism by flow cytometry. Besides, the potential effect of TQ, PIP, and SOR treatment on genome methylation and acetylation by determination of DNA methyltransferase (DNMT3B), histone deacetylase (HDAC3) and miRNA-29c expression levels. Finally, a molecular docking study was performed to propose potential mechanisms of action and binding affinity of TQ, PIP, and SOR with DNMT3B and HDAC3.

Results

Collectively, our data show that combinations of TQ and/or PIP with SOR have significantly enhanced the SOR anti-proliferative and cytotoxic effects depending on the dose and cell line by enhancing G2/M phase arrest, inducing apoptosis, downregulation of DNMT3B and HDAC3 expression and upregulation of the tumor suppressor, miRNA-29c. Finally, the molecular docking study has identified strong interactions between SOR, PIP, and TQ with DNMT3B and HDAC3, inhibiting their normal oncogenic activities and leading to growth arrest and cell death.

Conclusion

This study reported TQ and PIP as enhancers of the antiproliferative and cytotoxic effects of SOR and addressed the mechanisms, and identified molecular targets involved in their action.
Altruism in medical education: assessing attitudes of hospital in-patients towards face-to-face contact with medical students during the COVID-19 pandemic
Authors: Gritzner Alison , Scurr Thomas , Pearce Catharine , Sorrell Lexy , Dalton Georgina , Solola Joseph , Derry David
Published: March 2023

Background

Limited research indicated patients were largely amenable to seeing medical students pre-pandemic. However, the COVID-19 pandemic has highlighted the potential risk of nosocomial transmission and harm to patients from students. Patient opinions regarding these risks remain unexplored, which impacts elicitation of informed consent. We aim to identify these, and explore whether reflection on the risks and benefits of direct student interaction influenced patients’ attitudes. For guidance, we further explored measures to reduce perceived infection risk.

Method

We designed an original questionnaire for a cross-sectional study, completed by 200 inpatients from 25 wards between 18/02 and 16/03/2022 at Derriford Hospital, Plymouth. Patients in intensive care, with active COVID-19 infection or unable to comprehend the study information were excluded. The responses of a guardian were recorded for inpatients under 16. 17 questions were included - the initial question, reporting willingness to talk with and be examined by students, was repeated following nine questions exploring risks and benefits of student interaction. A further four questions addressed reducing the perceived infection risk. Data is summarised using frequencies and percentages, and with Wilcoxon signed-rank and rank-sum tests of association.

Results

85.4% (169/198) of participants gave an initial positive response to seeing medical students, and despite a third of participants changing their response 87.9% (174/197) remained willing after the survey resulting in no significant change. Furthermore, 87.2% (41/47) of those who perceived themselves at severe risk of harm from COVID-19 remained happy to see students. Participants reported reassurance knowing students were: fully vaccinated (76.0%); wearing masks (71.5%); lateral flow test negative within the last week (68.0%) and wearing gloves and gown (63.5%).

Conclusion

This study demonstrated the willingness of patients to engage in medical education despite recognised risks. Patient reflection on the risks and benefits of student interaction did not significantly reduce numbers willing to see students. Even those perceiving a risk of serious harm remained happy to have direct student contact – a demonstration of altruism in medical education. This suggests informed consent should include discussion of infection control measures, risks and benefits to patients and students, and offer alternatives to direct inpatient contact.
Wavy changes in the whiskers of domestic cats are correlated with feline leukemia virus infection
Authors: Morishita Masataka , Sunden Yuji , Horiguchi Misaki , Sakoya Hirosei , Yokogawa Mana , Ino Hiroyuki , Une Satoshi , Kawata Mutsumi , Hosoido Taisei , Morita Takehito
Published: March 2023

Background

Feline leukemia virus (FeLV) is a retrovirus with global impact on the health of domestic cats and is usually examined by serology. In our daily clinical practice, we noticed that cats infected with FeLV often possess wavy whiskers (sinus hairs on the face). To investigate the relationship between wavy whiskers (WW) and FeLV infection, the association between the presence or absence of wavy changes in whiskers and serological FeLV infection was examined in a total of 358 cats including 56 cats possessing WW, using the chi-square test. The results of blood tests from 223 cases were subjected to multivariate analysis (logistic analysis). Isolated whiskers were observed under light microscopy, and upper lip tissues (proboscis) were subjected to histopathological and immunohistochemical analyses.

Results

The prevalence of WW was significantly correlated with FeLV antigen positivity in the blood. Of 56 cases with WW, 50 (89.3%) were serologically positive for FeLV. The significant association between WW and serological FeLV positivity was also confirmed by multivariate analysis. In WW, narrowing, degeneration, and tearing of the hair medulla were observed. Mild infiltration of mononuclear cells in the tissues, but no degeneration or necrosis, was found. By immunohistochemistry, FeLV antigens (p27, gp70 and p15E) were observed in various epithelial cells including the sinus hair follicular epithelium of the whisker.

Conclusions

The data suggest that the wavy changes in whiskers, a unique and distinctive external sign on a cat’s face, were associated with FeLV infection.
Maternal obesity and gestational diabetes reprogram the methylome of offspring beyond birth by inducing epigenetic signatures in metabolic and developmental pathways
Authors: Alba-Linares Juan José , Pérez Raúl F. , Tejedor Juan Ramón , Bastante-Rodríguez David , Ponce Francisco , Carbonell Nuria García , Zafra Rafael Gómez , Fernández Agustín F. , Fraga Mario F. , Lurbe Empar
Published: March 2023

Background

Obesity is a negative chronic metabolic health condition that represents an additional risk for the development of multiple pathologies. Epidemiological studies have shown how maternal obesity or gestational diabetes mellitus during pregnancy constitute serious risk factors in relation to the appearance of cardiometabolic diseases in the offspring. Furthermore, epigenetic remodelling may help explain the molecular mechanisms that underlie these epidemiological findings. Thus, in this study we explored the DNA methylation landscape of children born to mothers with obesity and gestational diabetes during their first year of life.

Methods

We used Illumina Infinium MethylationEPIC BeadChip arrays to profile more than 770,000 genome-wide CpG sites in blood samples from a paediatric longitudinal cohort consisting of 26 children born to mothers who suffered from obesity or obesity with gestational diabetes mellitus during pregnancy and 13 healthy controls (measurements taken at 0, 6 and 12 month; total N = 90). We carried out cross-sectional and longitudinal analyses to derive DNA methylation alterations associated with developmental and pathology-related epigenomics.

Results

We identified abundant DNA methylation changes during child development from birth to 6 months and, to a lesser extent, up to 12 months of age. Using cross-sectional analyses, we discovered DNA methylation biomarkers maintained across the first year of life that could discriminate children born to mothers who suffered from obesity or obesity with gestational diabetes. Importantly, enrichment analyses suggested that these alterations constitute epigenetic signatures that affect genes and pathways involved in the metabolism of fatty acids, postnatal developmental processes and mitochondrial bioenergetics, such as CPT1B, SLC38A4, SLC35F3 and FN3K. Finally, we observed evidence of an interaction between developmental DNA methylation changes and maternal metabolic condition alterations.

Conclusions

Our observations highlight the first six months of development as being the most crucial for epigenetic remodelling. Furthermore, our results support the existence of systemic intrauterine foetal programming linked to obesity and gestational diabetes that affects the childhood methylome beyond birth, which involves alterations related to metabolic pathways, and which may interact with ordinary postnatal development programmes.
Epicardial adipose tissue density is a better predictor of cardiometabolic risk in HFpEF patients: a prospective cohort study
Authors: Liu Jie , Yu Qi , Li Ziyang , Zhou Yujiao , Liu Zhiqiang , You Linna , Tao Li , Dong Qian , Zuo Ziyu , Gao Lei , Zhang Dongying
Published: March 2023

Background

Epicardial adipose tissue (EAT) accumulation is associated with multiple cardiometabolic risk factors and prognosis of heart failure with preserved ejection fraction (HFpEF). The correlation between EAT density and cardiometabolic risk and the effect of EAT density on clinical outcome in HFpEF remain unclear. We evaluated the relationship between EAT density and cardiometabolic risk factors, also the prognostic value of EAT density in patients with HFpEF.

Methods

We included 154 HFpEF patients who underwent noncontrast cardiac computed tomography (CT) and all patients received follow-up. EAT density and volume were quantified semi-automatically. The associations of EAT density and volume with cardiometabolic risk factors, metabolic syndrome and the prognostic impact of EAT density were analyzed.

Results

Lower EAT density was associated with adverse changes in cardiometabolic risk factors. Each 1 HU increase in fat density, BMI was 0.14 kg/m2 lower (95% CI 0.08–0.21), waist circumference was 0.34 cm lower (95% CI 0.12–0.55), non-HDL-cholesterol was 0.02 mmol/L lower (95% CI 0–0.04), triglyceride was 0.03 mmol/L lower (95% CI 0.01–0.04), fasting plasma glucose was 0.05 mmol/L lower (95% CI 0.02–0.08), TyG index was 0.03 lower (95% CI 0.02–0.04), Log2(TG/HDL-C) was 0.03 lower (95% CI 0.02–0.05), METS-IR was 0.36 lower (95% CI 0.23–0.49), MetS Z-score was 0.04 lower (95% CI 0.02–0.06), and Log2(CACS + 1) was 0.09 lower (95% CI 0.02–0.15). After adjusting for BMI and EAT volume, the associations of non-HDL-cholesterol, triglyceride, fasting plasma glucose, insulin resistance indexes, MetS Z-score, and CACS with fat density remained significant. The area under the curve (AUC) for the presence and severity of metabolic syndrome was greater in EAT density than volume (AUC: 0.731 vs 0.694, 0.735 vs 0.662, respectively). Over a median follow-up of 16 months, the cumulative incidence of heart failure readmission and composite endpoint increased with lower level of EAT density (both p < 0.05).

Conclusions

EAT density was an independent impact factor of cardiometabolic risk in HFpEF. EAT density might have better predictive value than EAT volume for metabolic syndrome and it might have prognostic value in patients with HFpEF.
A novel clinical diagnostic marker predicting the relationship between visceral adiposity and renal function evaluated by estimated glomerular filtration rate (eGFR) in the Chinese physical examination population
Authors: Xu Yanping , Wang Xin Yi , Liu Haiping , Jin Dongzhen , Song Xiaoxiao , Wang Shengyao , Zhou Xinhe , Shi Mengte , Zheng Chao , Su Xiaoyou
Published: March 2023

Background and aims

The effect of body fat deposition on the kidney has received increasing attention. The Chinese visceral adiposity index (CVAI) is an important indicator of recent research. The purpose of this study was to explore the predictive value of CVAI and other organ obesity indicators in predicting CKD in Chinese residents.

Methods

A retrospective cross-sectional study of 5355 subjects was performed. First, the study utilized locally estimated scatterplot smoothing to describe the dose–response relationship between the estimated glomerular filtration rate (eGFR) and CVAI. The L1-penalized least absolute shrinkage and selection operator (LASSO) regression algorithm was used for covariation screening, and the correlation between CVAI and eGFR was quantified using multiple logistic regression. At the same time, the diagnostic efficiency of CVAI and other obesity indicators was evaluated by ROC curve analysis.

Results

CVAI and eGFR were negatively correlated. Using group one as the control, an odds ratio (OR) was calculated to quantify CVAI quartiles (ORs of Q2, Q3, and Q4 were 2.21, 2.99, and 4.42, respectively; P for trend < 0.001). CVAI had the maximum area under the ROC curve compared with other obesity indicators, especially in the female population (AUC: 0.74, 95% CI: 0.71–0.76).

Conclusions

CVAI is closely linked to renal function decline and has certain reference value for the screening of CKD patients, particularly in women.
Metagenomic analysis examines oral microbiome changes and interplay with immune response following prenatal total oral rehabilitation
Authors: Wu Tong Tong , Sohn Michael , Manning Samantha , Beblavy Robert , Gill Steven , Quataert Sally , Vasani Shruti , Jang Hoonji , Zeng Yan , Bruno Jennifer , Vazquez Adriana , Fiscella Kevin , Xiao Jin
Published: March 2023

Background

Suboptimal maternal oral health during pregnancy is potentially associated with adverse birth outcomes and increased dental caries risks in children. This study aimed to assess the oral microbiome and immune response following an innovative clinical regimen, Prenatal Total Oral Rehabilitation (PTOR), that fully restores women’s oral health to a “disease-free status” before delivery.

Methods

This prospective cohort study assessed 15 pregnant women at baseline and 3 follow-up visits (1 week, 2 weeks, and 2 months) after receiving PTOR. The salivary and supragingival plaque microbiomes were analyzed using metagenomic sequencing. Multiplexed Luminex cytokine assays were performed to examine immune response following PTOR. The association between salivary immune markers and oral microbiome was further examined.

Results

PTOR was associated with a reduction of periodontal pathogens in plaque, for instance, a lower relative abundance ofTannerella forsythiaandTreponema denticolaat 2 weeks compared to the baseline (p < 0.05). The alpha diversity of plaque microbial community was significantly reduced at the 1-week follow-up (p < 0.05). Furthermore, we observed significant changes in theActinomyces defective-associated carbohydrate degradation pathway andStreptococcus Gordonii-associated fatty acid biosynthesis pathway. Two immune markers related to adverse birth outcomes significantly differed between baseline and follow-up. ITAC, negatively correlated with preeclampsia severity, significantly increased at 1-week follow-up; MCP-1, positively correlated with gestational age, was elevated at 1-week follow-up. Association modeling between immune markers and microbiome further revealed specific oral microorganisms that are potentially correlated with the host immune response.

Conclusions

PTOR is associated with alteration of the oral microbiome and immune response among a cohort of underserved US pregnant women. Future randomized clinical trials are warranted to comprehensively assess the impact of PTOR on maternal oral flora, birth outcomes, and their offspring’s oral health.
Exome sequencing analysis of gastric primary myeloid sarcoma with monocytic differentiation with altered immunophenotype after chemotherapy: case report
Authors: Li Xiang , Zhang Hongxia , Cui Yong , Zhang Haijun , Wang Yonggang , Ding Meili , Zhu Xingyao , Zhang Ruiqi , Hu Qi , Tao Lin , Hu Wenhao , Li Xinxia , AO Qilin , Zou Hong
Published: March 2023

Background

Myeloid Sarcoma with monocytic differentiation is rare and quite likely is missed by surgical pathologists. However it is frequently misdiagnosed because of its non-specific imaging and histological pattern.

Case presentation

We report the case of a 64-year-old woman with gastric primary myeloid sarcoma with monocytic differentiatio. Upper endoscopy revealed a neoplastic growth at the junction of the lesser curvature and gastric antrum. Except for a slightly increased peripheral monocyte count, no abnormalities were found on hematological and bone-marrow examination. Gastroscopic biopsy showed poorly differentiated atypical large cells with visible nucleoli and nuclear fission. Immunohistochemistry showed positive CD34, CD4, CD43, and CD56 expression, and weakly positive lysozyme expression. Immune markers for poorly differentiated adenocarcinoma, malignant melanoma, and lymphohematopoietic-system tumors were negative. The final diagnosis was myeloid sarcoma with monocytic differentiation. Chemotherapy did not shrink the tumor, so, radical surgery was performed. Although the tumor morphology did not change postoperatively, the immunophenotype did. CD68 and lysozyme expression (tumor tissue markers) changed from negative and weakly positive to strongly positive, AE1/3 expression (epithelial marker) changed from negative to positive, and CD34, CD4, CD43, and CD56 expression (common in naive hematopoietic cell-derived tumors) was greatly attenuated. Exome sequencing revealed missense mutations in FLT3 and PTPRB, which are associated with myeloid sarcoma, and in TP53, CD44, CD19, LTK, NOTCH2, and CNTN2, which are associated with lymphohematopoietic tumors and poorly differentiated cancers.

Conclusion

We diagnosed myeloid sarcoma with monocytic differentiation after excluding poorly differentiated adenocarcinoma, common lymphohematopoietic-system tumors, epithelioid sarcoma, and malignant melanoma. We identified that the immunophenotypic of patient had alterations after chemotherapy, and FLT3 gene mutations. We hope that the above results will improve our understanding of this rare tumor.
Peat-based hairy root transformation using Rhizobium rhizogenes as a rapid and efficient tool for easily exploring potential genes related to root-knot nematode parasitism and host response
Authors: Zhang Xu , Li Shihui , Li Xin , Song Mengyuan , Ma Si , Tian Yongqiang , Gao Lihong
Published: March 2023

Background

Root-knot nematodes (RKNs) pose a worldwide threat to agriculture of many crops including cucumber. Genetic transformation (GT) has emerged as a powerful tool for exploration of plant-RKN interactions and genetic improvement of RKN resistance. However, it is usually difficult to achieve a highly efficient and stable GT protocol for most crops due to the complexity of this process.

Results

Here we firstly applied the hairy root transformation system in exploring root-RKN interactions in cucumber plants and developed a rapid and efficient tool transformation using Rhizobium rhizogenes strain K599. A solid-medium-based hypocotyl-cutting infection (SHI) method, a rockwool-based hypocotyl-cutting infection (RHI) method, and a peat-based cotyledon-node injection (PCI) method was evaluated for their ability to induce transgenic roots in cucumber plants. The PCI method generally outperformed the SHI and RHI methods for stimulating more transgenic roots and evaluating the phenotype of roots during nematode parasitism. Using the PCI method, we generated the CRISPR/Cas9-mediated malate synthase (MS) gene (involved in biotic stress responses) knockout plant and the LATERAL ORGAN BOUNDARIES-DOMAIN 16 (LBD16, a potential host susceptibility gene for RKN) promoter-driven GUS expressing plant. Knockout of MS in hairy roots resulted in effective resistance against RKNs, while nematode infection induced a strong expression of LBD16-driven GUS in root galls. This is the first report of a direct link between these genes and RKN performance in cucumber.

Conclusion

Taken together, the present study demonstrates that the PCI method allows fast, easy and efficient in vivo studies of potential genes related to root-knot nematode parasitism and host response.
Repair of anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) by sinus pouch technique
Authors: Kumae Masaru , Aoki Mitsuru , Hagino Ikuo , Koshiyama Hiroshi , Ito Takahiro , Nishiori Hironobu
Published: March 2023

A 5-month-old girl, weighing 5.3 kg, diagnosed ALCAPA underwent emergency surgery. The left coronary artery (LCA) originated from the posterior pulmonary artery (PA), and the left main trunk (LMT) was very short (1.5 mm), with moderate level of mitral valve regurgitation (MR). The distance from the origin to the pulmonary valve (Pv) was also short. A free extension conduit was created using adjacent sinus Valsalva flaps and implanted in the ascending aorta to avoid distortion of the coronary artery and the Pv.
The psychosocial consequences of covid-19 in adolescents with nonsuicidal self-injury
Authors: Zetterqvist M. , Landberg Å. , Jonsson L. S. , Svedin C. G.
Published: March 2023

Background

Young people have been especially affected by the psychosocial consequences of the covid-19 pandemic. Covid-19 has potentially also been more stressful for vulnerable groups with mental health problems.

Methods

In this cross-sectional study, the psychosocial effects of covid-19 in a vulnerable group of adolescents with nonsuicidal self-injury (NSSI) from a sample of 1602 Swedish high-school students were examined. Data were collected in 2020 and 2021. First, adolescents with and without NSSI were compared on how they perceived the psychosocial impact of covid-19, and second, a hierarchical multiple regression analysis was used to examine whether lifetime NSSI experience was associated with perceived psychosocial consequences of covid-19, when demographic variables and symptoms of mental health problems were controlled for. Interaction effects were also examined.

Results

Significantly more individuals with NSSI reported being burdened by covid-19 compared to those without NSSI. When demographic variables and mental health symptoms were controlled for, adding NSSI experience did not, however, increase the amount of variance explained in the model. The total model explained 23.2% of the variance in perceived psychosocial impact of covid-19. Perceiving the family’s financial situation as poor and neither good nor bad, studying a theoretical high school program, symptoms of depression and difficulties with emotion regulation were significantly associated with perceived negative psychosocial impact of the covid-19 pandemic. There was a significant interaction effect between NSSI experience and depressive symptoms. The effect of NSSI experience was larger when depressive symptoms were lower.

Conclusions

Lifetime NSSI experience in itself was not associated with psychosocial covid-19 consequences when other variables were controlled for, whereas symptoms of depression and difficulties with emotion regulation were. Results imply that vulnerable adolescents with mental health symptoms need special attention and access to mental health support in order to prevent further stress and worsening of mental health symptoms in the wake of the covid-19 pandemic.