bluuebunny/crossref_metadata_2025 huggingface dataset:
Endured and prevailed: a phenomenological study of doctors’ first year of clinical practice
Authors: Coakley Niamh , O’Leary Paula , Bennett Deirdre
Published: February 2023

Context

The challenging nature of the transition from medical student to doctor is highlighted by the associated negative consequences to new doctors’ mental health and wellbeing. Enhanced understanding of the lived experience of recent medical graduates as they move through the stages of transition over the first year of practice can inform interventions to ease the difficulties encountered.

Methods

Using interpretative phenomenological analysis (IPA), a novel approach to this topic, we explored the lived experience of transition from student to doctor over the first year of practice after graduation. Twelve new graduates were purposively recruited. We conducted semi-structured interviews at the end of their first year of practice with respect to their experience over the first year.

Results

The experience of transition was characterised by overlapping temporal stages. Participants’ initial adjustment period was characterised by shock, coping and stabilisation. A phase of development followed, with growth in confidence and a focus on self-care. Adversity was experienced in the form of interprofessional tensions, overwork, isolation and mistreatment. Finally, a period of reflection and rationalisation marked the end of the first year.

Discussion

Following initial anxiety regarding competence and performance, participants’ experience of transition was predominantly influenced by cultural, relational and contextual aspects of clinical practice. Solutions to ease this challenging time include stage-specific transitional interventions, curricular change at both undergraduate and postgraduate levels and a re-evaluation of the clinical learning environment to mitigate the difficulties endured.
PEEP application during mechanical ventilation contributes to fibrosis in the diaphragm
Authors: Qian Xiaoli , Jiang Ye , Jia Jianwei , Shen Weimin , Ding Yuejia , He Yuhan , Xu Peifeng , Pan Qing , Xu Ying , Ge Huiqing
Published: February 2023

Background

Positive end-expiratory airway pressure (PEEP) is a potent component of management for patients receiving mechanical ventilation (MV). However, PEEP may cause the development of diaphragm remodeling, making it difficult for patients to be weaned from MV. The current study aimed to explore the role of PEEP in VIDD.

Methods

Eighteen adult male New Zealand rabbits were divided into three groups at random: nonventilated animals (the CON group), animals with volume-assist/control mode without/ with PEEP 8 cmH2O (the MV group/ the MV + PEEP group) for 48 h with mechanical ventilation. Ventilator parameters and diaphragm were collected during the experiment for further analysis.

Results

There was no difference among the three groups in arterial blood gas and the diaphragmatic excursion during the experiment. The tidal volume, respiratory rate and minute ventilation were similar in MV + PEEP group and MV group. Airway peak pressure in MV + PEEP group was significantly higher than that in MV group (p < 0.001), and mechanical power was significantly higher (p < 0.001). RNA-seq showed that genes associated with fibrosis were enriched in the MV + PEEP group. This results were further confirmed on mRNA expression. As shown by Masson’s trichrome staining, there was more collagen fiber in the MV + PEEP group than that in the MV group (p = 0.001). Sirius red staining showed more positive staining of total collagen fibers and type I/III fibers in the MV + PEEP group (p = 0.001; p = 0.001). The western blot results also showed upregulation of collagen types 1A1, III, 6A1 and 6A2 in the MV + PEEP group compared to the MV group (p < 0.001, all). Moreover, the positive immunofluorescence of COL III in the MV + PEEP group was more intense (p = 0.003). Furthermore, the expression of TGF-β1, one of the most potent fibrogenic factors, was upregulated at both the mRNA and protein levels in the MV + PEEP group (mRNA: p = 0.03; protein: p = 0.04).

Conclusions

We demonstrated that PEEP application for 48 h in mechanically ventilated rabbits will cause collagen deposition and fibrosis in the diaphragm. Moreover, activation of the TGF-β1 signaling pathway and myofibroblast differentiation may be the potential mechanism of this diaphragmatic fibrosis. These findings might provide novel therapeutic targets for PEEP application-induced diaphragm dysfunction.
Strain evaluation of axially loaded collateral ligaments: a comparison of digital image correlation and strain gauges
Authors: Prusa Gwendolin , Bauer Leandra , Santos Inês , Thorwächter Christoph , Woiczinski Matthias , Kistler Manuel
Published: February 2023

The response of soft tissue to loading can be obtained by strain assessment. Typically, strain can be measured using electrical resistance with strain gauges (SG), or optical sensors based on the digital image correlation (DIC), among others. These sensor systems are already established in other areas of technology. However, sensors have a limited range of applications in medical technology due to various challenges in handling human soft materials. The aim of this study was to compare directly attached foil-type SG and 3D-DIC to determine the strain of axially loaded human ligament structures. Therefore, the medial (MCL) and lateral (LCL) collateral ligaments of 18 human knee joints underwent cyclic displacement-controlled loading at a rate of 20 mm/min in two test trials. In the first trial, strain was recorded with the 3D-DIC system and the reference strain of the testing machine. In the second trial, strain was additionally measured with a directly attached SG. The results of the strain measurement with the 3D-DIC system did not differ significantly from the reference strain in the first trial. The strains assessed in the second trial between reference and SG, as well as between reference and 3D-DIC showed significant differences. This suggests that using an optical system based on the DIC with a given unrestricted view is an effective method to measure the superficial strain of human ligaments. In contrast, directly attached SGs provide only qualitative comparable results. Therefore, their scope on human ligaments is limited to the evaluation of changes under different conditions.
Antiviral therapy inhibited HBV-reactivation and improved long-term outcomes in patients who underwent radiofrequency ablation for HBV-related hepatocellular carcinoma
Authors: Liu Jian , Shen Hao , Huang Shengyu , Lin Jianbo , Yan Zhenlin , Qian Guojun , Lu Zhenghua , Wan Xuying , Zhang Fabiao , Wang Kui , Zhang Yongjie , Li Jun
Published: February 2023

Background

Hepatitis B virus (HBV) reactivation impact negatively the prognosis of patients with HBV-related hepatocellular carcinoma (HCC). This study aimed to observe the effect of antiviral therapy (AVT) on viral reactivation and long-term outcomes after percutaneous radiofrequency ablation (PRFA) for HBV-related HCC.

Methods

Data on 538 patients between 2009 and 2013 were reviewed. Propensity score matching (PSM) analysis was used to adjust for differences in baseline features between patients who received AVT (AVT group) and did not receive it (non-AVT group). Logistic regression was used to identify the independent factors for viral reactivation. The tumor recurrence and overall survival (OS) rates were analyzed using the Kaplan–Meier method. Recurrence patterns were also investigated.

Results

HBV reactivation developed in 10.8% (58/538) of patients after PRFA. AVT was associated independently with decreased viral reactivation (odd ratio: 0.061, 95% confidence interval: 0.018–0.200). In 215 pairs of patients obtained after PSM, the AVT group had lower 1-, 3-, and 5-year recurrence rates (24%, 55%, and 67% vs 33%, 75%, and 85%, respectively) and higher 1-, 3-, and 5-year OS rates (100%, 67%, and 59% vs 100%, 52%, and 42%, respectively) than non-AVT group (P < 0.001 for both). Additionally, the relapses in distant hepatic segments and the late recurrence after 2 years of PRFA were significantly reduced in the AVT group (78/215 vs 111/215 vs., P = 0.001; 39/109 vs. 61/91, P = 0.012, respectively).

Conclusions

AVT reduced late and distal intrahepatic recurrence and improved OS in patients undergoing PRFA for HBV-related HCC by inhibiting viral reactivation.
A large single-center prospective study to investigate the factors influencing the choice of breast-conserving surgery versus mastectomy in Chinese women with early breast cancer
Authors: Li Zhensheng , Liu Yunjiang , Zhang Jing , Li Yue , Du Kaiye , Zhang Shuo , Han Huina , Zhang Jun
Published: February 2023

Background

Compared to mastectomy, breast-conserving surgery (BCS) provides the same survival rate and a higher quality of life for patients with early breast cancer (EBC). However, Chinese women with EBC are known to have a low BCS rate. A large prospective cohort study was conducted to investigate the factors influencing the choice of BCS in this population.

Methods

In 2017, all women with unilateral EBC and eligible for BCS at our institution were enrolled. Before surgery, the patient’s trust in the surgeon and her perceived strength of the surgeon’s recommendation of BCS were measured through an in-person interview and validated ad hoc questionnaire. Multivariate logistic regressions on BCS procedure vs. mastectomy were used to estimate the odds ratio (OR).

Results

One thousand one hundred thirty-six patients enrolled at analysis had an average age of 51.8 and tumor size of 2.4 cm. 19.9% of patients had BCS. The “strong” level of trust in the surgeon was significantly associated with BCS with an OR of 2.944 (p<0.001) when compared to the “average or under” trust. The “strong” and “moderate” strengths in surgeon recommendation for BCS were also found to be significantly associated with the BCS procedure with ORs of 12.376 (p <0.001) and 1.757 (p =0.040), respectively, compared to the “neutral or dissuaded” strength.

Conclusions

Stronger trust in surgeons and BCS recommendation by surgeons are associated with a higher rate of BCS in Chinese women with EBC. Interventional trials are needed to confirm this finding.
Alternation of the gut microbiota in irritable bowel syndrome: an integrated analysis based on multicenter amplicon sequencing data
Authors: Chen Han , Ou Rong , Tang Nana , Su Wei , Yang Ruoyun , Yu Xin , Zhang Guoxin , Jiao Jianhua , Zhou Xiaoying
Published: February 2023

Background

Gut dysbacteriosis has been reported as one of the etiologies for irritable bowel syndrome (IBS). However, the association between gut microbiota and IBS is still inconclusive.

Method

A paired-sample study was designed by retrieving original multicenter 16 s-rRNA data of IBS patients and healthy controls from the GMrepo database. The propensity score matching (PSM) algorithm was applied to reduce confounding bias. The differential analysis of microbiota composition was performed at different taxonomic levels. The co-occurrence network was established. Subgroup analysis was performed to identify specific microbial compositions in different IBS subtypes.

Results

A total of 1522 amplicon samples were initially enrolled. After PSM, 708 individuals (354 IBS and 354 healthy controls) were eligible for further analysis. A total of 1,160 genera were identified. We identified significantly changed taxa in IBS groups (IBS-enriched: the families Enterobacteriaceae, Moraxellaceae and Sphingobacteriaceae; the genera Streptococcus, Bacillus, Enterocloster, Sphingobacterium, Holdemania and Acinetobacter. IBS-depleted: the phyla Firmicutes, Euryarchaeota, Cyanobacteria, Acidobacteria and Lentisphaerae; the families Bifidobacteriaceae, Ruminococcaceae, Methanobacteriaceae and the other 25 families; the genera Faecalibacterium, Bifidobacterium and other 68 genera). The co-occurrence network identified three hub genera and six hub species (including Faecalibacterium prausnitzii) that may be involved in IBS pathophysiology. Strong positive interactions were identified among the Bifidobacterium longum, Bifidobacterium breve and Bifidobacterium adolescentis in the Bifidobacterium community.

Conclusion

This study provides quantitative analysis and visualization of the interaction between the gut microbiota and IBS. The identification of key species should be further validated to evaluate their causal relationships with the pathogenesis of IBS.
Liquid biopsies: the future of cancer early detection
Authors: Connal Siobhan , Cameron James M. , Sala Alexandra , Brennan Paul M. , Palmer David S. , Palmer Joshua D. , Perlow Haley , Baker Matthew J.
Published: February 2023

Cancer is a worldwide pandemic. The burden it imposes grows steadily on a global scale causing emotional, physical, and financial strains on individuals, families, and health care systems. Despite being the second leading cause of death worldwide, many cancers do not have screening programs and many people with a high risk of developing cancer fail to follow the advised medical screening regime due to the nature of the available screening tests and other challenges with compliance. Moreover, many liquid biopsy strategies being developed for early detection of cancer lack the sensitivity required to detect early-stage cancers. Early detection is key for improved quality of life, survival, and to reduce the financial burden of cancer treatments which are greater at later stage detection. This review examines the current liquid biopsy market, focusing in particular on the strengths and drawbacks of techniques in achieving early cancer detection. We explore the clinical utility of liquid biopsy technologies for the earlier detection of solid cancers, with a focus on how a combination of various spectroscopic and -omic methodologies may pave the way for more efficient cancer diagnostics.
A transdermal treatment with MC903 ameliorates diet-induced obesity by reducing visceral fat and increasing myofiber thickness and energy consumption in mice
Authors: Wada Tsutomu , Miyazawa Yuichiro , Ikurumi Misa , Fuse Kento , Okekawa Akira , Onogi Yasuhiro , Saito Shigeru , Tsuneki Hiroshi , Sasaoka Toshiyasu
Published: February 2023

Aim

MC903 is a synthetic derivative of vitamin D3 that has been designed to diminish its impact on calcium metabolism and is clinically used as a transdermal reagent for psoriasis. Animal studies showed that an oral or intraperitoneal vitamin D3 treatment prevented the development of obesity. In contrast, the bioavailability of orally administered vitamin D3 is reported to be low in obese patients. In the current study, we aimed to investigate the impact of a transdermal treatment with MC903 in established obese mice. We further studied the underlying mechanisms of MC903-mediated metabolic improvement.

Materials and methods

Male C57BL/6 J mice were fed standard chow or a 60% high-fat diet (HFD) for 7 weeks, and a transdermal treatment with MC903 on the ear auricle was initiated thereafter. The metabolic profiles of mice were analyzed during 4 weeks of treatment, and mice were dissected for histological and gene expression analyses. The direct impacts of MC903 and vitamin D3 were investigated using 3T3-L1 adipocytes and C2C12 myotubes in vitro.

Results

HFD-fed mice showed significant increases in body and epididymal white adipose tissue (eWAT) weights with enlarged adipocytes. They exhibited glucose intolerance, decreased oxygen consumption, and chronic inflammation in eWAT. The transdermal treatment with MC903 significantly ameliorated these metabolic abnormalities in HFD-fed mice without affecting food consumption. In accordance with enhanced energy metabolism, myofiber diameters and the expression of uncoupling protein 3 (UCP3) in the gastrocnemius and soleus muscle were significantly increased in MC903-treated HFD mice. In addition, vitamin D3 and MC903 both suppressed adipogenic differentiation and enhanced lipolysis in 3T3-L1 adipocytes, and increased UCP3 expression in cultured C2C12 myotubes. Furthermore, MC903 increased oxygen consumption and UCP3 knockdown significantly decreased them in C2C12 myotubes.

Conclusions

A transdermal treatment with MC903 increased myofiber diameter and energy metabolism and decreased visceral fat accumulation, thereby improving obesity and glucose intolerance in mice.
Diffuse pulmonary meningotheliomatosis with pan-TRK expression by immunohistochemistry: a novel finding and potential pitfall
Authors: Karakas Cansu , Nead Michael A. , Velez Moises J.
Published: February 2023

Background

Pulmonary meningothelial-like nodules (PMNs) are benign proliferations of unclear clinical significance. They are mainly asymptomatic lesions that are usually discovered during the pathologic evaluation of resected pulmonary specimens or following post-mortem examination. Diffuse pulmonary meningotheliomatosis (DPM), which presents as bilateral multiple PMNs throughout the lungs, has been described less frequently. DPMs are benign lesions associated with both neoplastic and non-neoplastic pulmonary conditions.

Case presentation

We report the case of a 59-year-old female patient who presented with a history of cough. Computerized tomography (CT) imaging revealed multiple subcentimeter bilateral pulmonary nodules. transbronchial biopsies were obtained which revealed foci of nodular interstitial proliferations composed of epithelioid to spindled cells in a vague whorled pattern. Immunohistochemical stains were diffusely positive for EMA and progesterone receptor. Furthermore, pan-TRK exhibited strong and diffuse membranous expression in the lesional cells. INSM1 was negative for expression. RNA-based next-generation sequencing for the detection of NTRK fusions was performed and was negative for gene rearrangements involving NTRK1, NTRK2, and NTRK3.

Conclusion

Here, we report a rare case of DPM and report pan-TRK expression in PMNs which has not been described. We provide a brief review of the literature and provide insight into the potential physiologic nature of PMNs. Lastly, we emphasize the recognition of pan-TRK immunoexpression in PMNs to avoid potential diagnostic errors.
Return to work following primary total hip arthroplasty: a systematic review and meta-analysis
Authors: Soleimani Mohammad , Babagoli Mazyar , Baghdadi Soroush , Mirghaderi Peyman , Fallah Yousef , Sheikhvatan Mehrdad , Shafiei Seyyed Hossein
Published: February 2023

Background

Total hip arthroplasty (THA) is increasingly common in younger patients, who are more likely to be working preoperatively. There is a need for an updated review of the literature regarding the rate and time to return to work (RTW), which is important when counseling patients, and also from an economic standpoint.

Methods

A systematic review and meta-analysis of the literature was performed on January 20, 2022, and studies reporting the rate and/or time to RTW after THA were included. Two authors independently selected relevant papers. RTW was extracted and analyzed using fixed-effects or random-effects models where appropriate.

Results

A total of 48 studies were included in the final analysis. We found that 70.7% of patients were working after primary THA. Among patients who were working before surgery, this rate increases to 87.9%, while 28.1% of patients who were not working preoperatively started working after surgery. Younger patients were more likely to RTW, while patients with a physically demanding job were less likely to RTW. Minimally invasive techniques were reported to yield a higher rate of RTW and an earlier time to RTW.

Conclusion

We found that the majority of patients return to work after THA, and some patients are able to start working after surgery. Compared to previous reviews, patients seem to have a higher rate and earlier RTW. The overall trend of the literature suggests that patients are returning to work earlier and at a higher rate compared to previous reviews.
Mobility of mPing and its associated elements is regulated by both internal and terminal sequences
Authors: Redd Priscilla S. , Diaz Stephanie , Weidner David , Benjamin Jazmine , Hancock C. Nathan
Published: February 2023

Background

DNA transposable elements are mobilized by a “cut and paste” mechanism catalyzed by the binding of one or more transposase proteins to terminal inverted repeats (TIRs) to form a transpositional complex. Study of the rice genome indicates that the mPing element has experienced a recent burst in transposition compared to the closely related Ping and Pong elements. A previously developed yeast transposition assay allowed us to probe the role of both internal and terminal sequences in the mobilization of these elements.

Results

We observed that mPing and a synthetic mPong element have significantly higher transposition efficiency than the related autonomous Ping and Pong elements. Systematic mutation of the internal sequences of both mPing and mPong identified multiple regions that promote or inhibit transposition. Simultaneous alteration of single bases on both mPing TIRs resulted in a significant reduction in transposition frequency, indicating that each base plays a role in efficient transposase binding. Testing chimeric mPing and mPong elements verified the important role of both the TIRs and internal regulatory regions. Previous experiments showed that the G at position 16, adjacent to the 5′ TIR, allows mPing to have higher mobility. Alteration of the 16th and 17th base from mPing’s 3′ end or replacement of the 3′ end with Pong 3′ sequences significantly increased transposition frequency.

Conclusions

As the transposase proteins were consistent throughout this study, we conclude that the observed transposition differences are due to the element sequences. The presence of sub-optimal internal regions and TIR bases supports a model in which transposable elements self-limit their activity to prevent host damage and detection by host regulatory mechanisms. Knowing the role of the TIRs, adjacent sub-TIRs, and internal regulatory sequences allows for the creation of hyperactive elements.
DNA methylation in peripheral blood leukocytes for the association with glucose metabolism and invasive breast cancer
Authors: Jung Su Yon , Bhatti Parveen , Pellegrini Matteo
Published: February 2023

Background

Insulin resistance (IR) is a well-established factor for breast cancer (BC) risk in postmenopausal women, but the interrelated molecular pathways on the methylome are not explicitly described. We conducted a population-level epigenome-wide association (EWA) study for DNA methylation (DNAm) probes that are associated with IR and prospectively correlated with BC development, both overall and in BC subtypes among postmenopausal women.

Methods

We used data from Women’s Health Initiative (WHI) ancillary studies for our EWA analyses and evaluated the associations of site-specific DNAm across the genome with IR phenotypes by multiple regressions adjusting for age and leukocyte heterogeneities. For our analysis of the top 20 IR-CpGs with BC risk, we used the WHI and the Cancer Genomic Atlas (TCGA), using multiple Cox proportional hazards and logit regressions, respectively, accounting for age, diabetes, obesity, leukocyte heterogeneities, and tumor purity (for TCGA). We further conducted a Gene Set Enrichment Analysis.

Results

We detected several EWA-CpGs in TXNIP, CPT1A, PHGDH, and ABCG1. In particular, cg19693031 in TXNIP was replicated in all IR phenotypes, measured by fasting levels of glucose, insulin, and homeostatic model assessment-IR. Of those replicated IR-genes, 3 genes (CPT1A, PHGDH, and ABCG1) were further correlated with BC risk; and 1 individual CpG (cg01676795 in POR) was commonly detected across the 2 cohorts.

Conclusions

Our study contributes to better understanding of the interconnected molecular pathways on the methylome between IR and BC carcinogenesis and suggests potential use of DNAm markers in the peripheral blood cells as preventive targets to detect an at-risk group for IR and BC in postmenopausal women.
Identification of m7G regulator-mediated RNA methylation modification patterns and related immune microenvironment regulation characteristics in heart failure
Authors: Ma Chaoqun , Tu Dingyuan , Xu Qiang , Wu Yan , Song Xiaowei , Guo Zhifu , Zhao Xianxian
Published: February 2023

Background

N7-methylguanosine (m7G) modification has been reported to regulate RNA expression in multiple pathophysiological processes. However, little is known about its role and association with immune microenvironment in heart failure (HF).

Results

One hundred twenty-four HF patients and 135 nonfailing donors (NFDs) from six microarray datasets in the gene expression omnibus (GEO) database were included to evaluate the expression profiles of m7G regulators. Results revealed that 14 m7G regulators were differentially expressed in heart tissues from HF patients and NFDs. Furthermore, a five-gene m7G regulator diagnostic signature, NUDT16, NUDT4, CYFIP1, LARP1, and DCP2, which can easily distinguish HF patients and NFDs, was established by cross-combination of three machine learning methods, including best subset regression, regularization techniques, and random forest algorithm. The diagnostic value of five-gene m7G regulator signature was further validated in human samples through quantitative reverse-transcription polymerase chain reaction (qRT-PCR). In addition, consensus clustering algorithms were used to categorize HF patients into distinct molecular subtypes. We identified two distinct m7G subtypes of HF with unique m7G modification pattern, functional enrichment, and immune characteristics. Additionally, two gene subgroups based on m7G subtype-related genes were further discovered. Single-sample gene-set enrichment analysis (ssGSEA) was utilized to assess the alterations of immune microenvironment. Finally, utilizing protein–protein interaction network and weighted gene co-expression network analysis (WGCNA), we identified UQCRC1, NDUFB6, and NDUFA13 as m7G methylation-associated hub genes with significant clinical relevance to cardiac functions.

Conclusions

Our study discovered for the first time that m7G RNA modification and immune microenvironment are closely correlated in HF development. A five-gene m7G regulator diagnostic signature for HF (NUDT16, NUDT4, CYFIP1, LARP1, and DCP2) and three m7G methylation-associated hub genes (UQCRC1, NDUFB6, and NDUFA13) were identified, providing new insights into the underlying mechanisms and effective treatments of HF.
The subcortical correlates of autistic traits in school-age children: a population-based neuroimaging study
Authors: Sharp T. H. , Elsabbagh M. , Pickles A. , Bedford R.
Published: February 2023

Background

There is emerging evidence that the neuroanatomy of autism forms a spectrum which extends into the general population. However, whilst several studies have identified cortical morphology correlates of autistic traits, it is not established whether morphological differences are present in the subcortical structures of the brain. Additionally, it is not clear to what extent previously reported structural associations may be confounded by co-occurring psychopathology. To address these questions, we utilised neuroimaging data from the Adolescent Brain Cognitive Development Study to assess whether a measure of autistic traits was associated with differences in child subcortical morphology, and if any observed differences persisted after adjustment for child internalising and externalising symptoms.

Methods

Our analyses included data from 7005 children aged 9–10 years (female: 47.19%) participating in the Adolescent Brain Cognitive Development Study. Autistic traits were assessed using scores from the Social Responsiveness Scale (SRS). Volumes of subcortical regions of interest were derived from structural magnetic resonance imaging data.

Results

Overall, we did not find strong evidence for an association of autistic traits with differences in subcortical morphology in this sample of school-aged children. Whilst lower absolute volumes of the nucleus accumbens and putamen were associated with higher scores of autistic traits, these differences did not persist once a global measure of brain size was accounted for.

Limitations

It is important to note that autistic traits were assessed using the SRS, of which higher scores are associated with general behavioural problems, and therefore may not be wholly indicative of autism-specific symptoms. In addition, individuals with a moderate or severe autism diagnosis were excluded from the ABCD study, and thus, the average level of autistic traits will be lower than in the general population which may bias findings towards the null.

Conclusions

These findings from our well-powered study suggest that other metrics of brain morphology, such as cortical morphology or shape-based phenotypes, may be stronger candidates to prioritise when attempting to identify robust neuromarkers of autistic traits.
The lack of specialized pediatric cardiac surgeons in Lebanon: a humanitarian catastrophe
Authors: Zeineddine Jana , El Chamieh Carolla , Bou Sanayeh Elie
Published: February 2023

Congenital heart disease (CHD) is a major public health concern, as it is the most common birth defect and the leading cause of death in the first year of life if adequate surgical interventions were not provided. Unfortunately, in Lebanon, a country that has been assailed by devastating social and economic crises, many specialized Lebanese pediatric heart surgeons fled abroad to secure more stable careers. This has led to the death of many newborns with CHDs. Public health authorities must find urgent solutions for this national tragedy that is projected to last for years.
Pastoralists’ and agro-pastoralists’ livelihood resilience to climate change-induced risks in the Borana zone, south Ethiopia: Using resilience index measurement approach
Authors: Tofu Daniel Assefa , Fana Chalchisa , Dilbato Tegegn , Dirbaba Niguse Bekele , Tesso Gutu
Published: February 2023

This study was conducted in the Borana zone, Oromia region, southern Ethiopia, with the aim of analysing the livelihood resilience of pastoralists’ and agro-pastoralists’ to climate change-related risks. A household survey was used to collect quantitative data, whereas qualitative data were collected via focus group discussions, expert group discussions, and personal observations. Descriptive statistics were used to analyse quantitative data, and content analysis was used to analyse qualitative data. The results show that frequent droughts, rising temperatures, and reduced rainfall are the major climate change-induced risks affecting the livelihoods of pastorals and agro-pastorals in the study area. Among the parameters tested, the greatest impacts of climate change-induced risks on pastoral and agro-pastoral livelihood systems were recorded for food [100%] and animal feed or pasture [99%], followed by livestock loss [95%], a decline in species dynamics [95%], and agro-pastoral land degradation [95%]. The average climate resilience index score of the Borena zone is found to be 0.328, implying that 32.8% of the respondents are resilient, with 0.163 [16.3%] pastoralists and 0.417 [41.7%] agro-pastoralists being resilient. However, all the results are below the scale of the minimum threshold [0.5 or 50%], implying that livelihoods and their households are poorly resilient. For the low resilience in Borena, limited access to basic services [0.26] and the adaptive capacity [0.29] of the pastoralists and agro-pastoralists contributed the highest share for resilience capacity compared to other major building blocks of resilience. However, of the two livelihood systems, pastoralists were found to have less resilience [0.249] compared to agro-pastoralists [0.407]. Besides the climatic factors, the resilience of pastoralists’ and agro-pastoralists’ livelihoods was affected positively and significantly by adaptive capacity and negatively and with statistical significance by the asset endowments of the households at P < 0.05. Therefore, policymakers should give pertinent attention to the reduction of the effects of climatic risks and increase the resilience of pastoral and agro-pastoral livelihood systems. Furthermore, actions that focus on increasing access to water, improving the rangeland generative capacity, diversifying the income sources, and providing timely and accurate early warning information are indispensable to building resilient livelihoods among the pastoral and agro-pastoral communities.
Outcomes in participants with ventilated nosocomial pneumonia and organ failure treated with ceftolozane/tazobactam versus meropenem: a subset analysis of the phase 3, randomized, controlled ASPECT-NP trial
Authors: Martin-Loeches Ignacio , Shorr Andrew F. , Wunderink Richard G. , Kollef Marin H. , Timsit Jean-François , Yu Brian , Huntington Jennifer A. , Jensen Erin , Bruno Christopher J.
Published: February 2023

Background

The pivotal ASPECT-NP trial showed ceftolozane/tazobactam was non-inferior to meropenem for the treatment of ventilated hospital-acquired/ventilator-associated bacterial pneumonia (vHABP/VABP). Here, we evaluated treatment outcomes by degree of respiratory or cardiovascular dysfunction.

Methods

This was a subset analysis of data from ASPECT-NP, a randomized, double-blind, non-inferiority trial (ClinicalTrials.gov NCT02070757). Adults with vHABP/VABP were randomized 1:1 to 3 g ceftolozane/tazobactam or 1 g meropenem every 8 h for 8–14 days. Outcomes in participants with a baseline respiratory component of the Sequential Organ Failure Assessment (SOFA) score (R-SOFA) ≥ 2 (indicative of severe respiratory failure), cardiovascular component of the SOFA score (CV-SOFA) ≥ 2 (indicative of shock), or R-SOFA ≥ 2 plus CV-SOFA ≥ 2 were compared by treatment arm. The efficacy endpoint of primary interest was 28-day all-cause mortality. Clinical response, time to death, and microbiologic response were also evaluated.

Results

There were 726 participants in the intention-to-treat population; 633 with R-SOFA ≥ 2 (312 ceftolozane/tazobactam, 321 meropenem), 183 with CV-SOFA ≥ 2 (84 ceftolozane/tazobactam, 99 meropenem), and 160 with R-SOFA ≥ 2 plus CV-SOFA ≥ 2 (69 ceftolozane/tazobactam, 91 meropenem). Baseline characteristics, including causative pathogens, were generally similar in participants with R-SOFA ≥ 2 or CV-SOFA ≥ 2 across treatment arms. The 28-day all-cause mortality rate was 23.7% and 24.0% [difference: 0.3%, 95% confidence interval (CI) − 6.4, 6.9] for R-SOFA ≥ 2, 33.3% and 30.3% (difference: − 3.0%, 95% CI − 16.4, 10.3) for CV-SOFA ≥ 2, and 34.8% and 30.8% (difference: − 4.0%, 95% CI − 18.6, 10.3), respectively, for R-SOFA ≥ 2 plus CV-SOFA ≥ 2. Clinical cure rates were as follows: 55.8% and 54.2% (difference: 1.6%, 95% CI − 6.2, 9.3) for R-SOFA ≥ 2, 53.6% and 55.6% (difference: − 2.0%, 95% CI − 16.1, 12.2) for CV-SOFA ≥ 2, and 53.6% and 56.0% (difference: − 2.4%, 95% CI − 17.6, 12.8), respectively, for R-SOFA ≥ 2 plus CV-SOFA ≥ 2. Time to death was comparable in all SOFA groups across both treatment arms. A higher rate of microbiologic eradication/presumed eradication was observed for CV-SOFA ≥ 2 and R-SOFA ≥ 2 plus CV-SOFA ≥ 2 with ceftolozane/tazobactam compared to meropenem.

Conclusions

The presence of severe respiratory failure or shock did not affect the relative efficacy of ceftolozane/tazobactam versus meropenem; either agent may be used to treat critically ill patients with vHABP/VABP.

Trial registration: ClinicalTrials.gov NCT02070757. Registered 25 February 2014, https://clinicaltrials.gov/ct2/show/NCT02070757
Critically ill patient mortality by age: long-term follow-up (CIMbA-LT)
Authors: Gonçalves-Pereira João , Oliveira André , Vieira Tatiana , Rodrigues Ana Rita , Pinto Maria João , Pipa Sara , Martinho Ana , Ribeiro Sofia , Paiva José-Artur
Published: February 2023

Background

The past years have witnessed dramatic changes in the population admitted to the intensive care unit (ICU). Older and sicker patients are now commonly treated in this setting due to the newly available sophisticated life support. However, the short- and long-term benefit of this strategy is scarcely studied.

Methods

The Critically Ill patients’ mortality by age: Long-Term follow-up (CIMbA-LT) was a multicentric, nationwide, retrospective, observational study addressing short- and long-term prognosis of patients admitted to Portuguese multipurpose ICUs, during 4 years, according to their age and disease severity. Patients were followed for two years after ICU admission. The standardized hospital mortality ratio (SMR) was calculated according to the Simplified Acute Physiology Score (SAPS) II and the follow-up risk, for patients discharged alive from the hospital, according to official demographic national data for age and gender. Survival curves were plotted according to age group.

Results

We included 37.118 patients, including 15.8% over 80 years old. The mean SAPS II score was 42.8 ± 19.4. The ICU all-cause mortality was 16.1% and 76% of all patients survive until hospital discharge. The SAPS II score overestimated hospital mortality [SMR at hospital discharge 0.7; 95% confidence interval (CI) 0.63–0.76] but accurately predicted one-year all-cause mortality [1-year SMR 1.01; (95% CI 0.98–1.08)]. Survival curves showed a peak in mortality, during the first 30 days, followed by a much slower survival decline thereafter. Older patients had higher short- and long-term mortality and their hospital SMR was also slightly higher (0.76 vs. 0.69). Patients discharged alive from the hospital had a 1-year relative mortality risk of 6.3; [95% CI 5.8–6.7]. This increased risk was higher for younger patients [21.1; (95% CI 15.1–39.6) vs. 2.4; (95% CI 2.2–2.7) for older patients].

Conclusions

Critically ill patients’ mortality peaked in the first 30 days after ICU admission. Older critically ill patients had higher all-cause mortality, including a higher hospital SMR. A long-term increased relative mortality risk was noted in patients discharged alive from the hospital, but this was more noticeable in younger patients.
pth-moment stability of stochastic functional differential equations with Markovian switching and impulsive control
Authors: Li Zhao
Published: February 2023

In this paper, we investigate the problem ofpth-moment stability of stochastic functional differential equations with Markovian switching and impulsive control via comparison principle. Employing stochastic analysis theory and an impulsive delay differential inequality, we establish a new comparison principle for stochastic functional differential equations with Markovian switching and impulsive control. Using the comparison principle, we derive sufficient conditions for stochastic functional differential equations with Markovian switching and impulsive control by the stability of impulsive delay differential equations. An example is provided to show the effectiveness of the proposed results.
Diagnostic efficiency on ultrasound shear wave elastography in evaluation of steatosis severity for non-alcoholic fatty liver disease: a rat model
Authors: Wu Yuhui , Liu Qianjiao , Wang Yan , Li Fangyan , Chan Lawrence Wing-Chi , Wen Yong , Yang Fan , Xiang Yining , Duan Qinghong , Luo Peng , Lei Pinggui
Published: February 2023

Background

The pathological feature of steatosis affects the elasticity values measured by shear wave elastography (SWE) is still controversial in non-alcoholic fatty liver disease (NAFLD). The aim of this study is to demonstrate the influence of steatosis on liver stiffness measured by SWE on a rat model with NAFLD and analyze feasibility of SWE for grading steatosis in absence of fibrosis.

Methods

Sixty-six rats were fed with methionine choline deficient diet or standard diet to produce various stages of steatosis; 48 rats were available for final analysis. Rats underwent abdominal ultrasound SWE examination and pathological assessment. Liver histopathology was analyzed to assess the degree of steatosis, inflammation, ballooning, and fibrosis according to the non-alcoholic fatty liver disease activity score. The diagnostic performance of SWE for differentiating steatosis stages was estimated according to the receiver operating characteristic (ROC) curve. Decision curve analysis (DCA) was conducted to determine clinical usefulness and the areas under DCA (AUDCAs) calculated.

Results

In multivariate analysis, steatosis was an independent factor affecting the mean elastic modules (B = 1.558, P < 0.001), but not inflammation (B =  − 0.031, P = 0.920) and ballooning (B = 0.216, P = 0.458). After adjusting for inflammation and ballooning, the AUROC of the mean elasticity for identifying S ≥ S1 was 0.956 (95%CI: 0.872–0.998) and the AUDCA, 0.621. The AUROC for distinguishing S ≥ S2 and S = S3 was 0.987 (95%CI: 0.951–1.000) and 0.920 (95%CI: 0.816–0.986) and the AUDCA was 0.506 and 0.256, respectively.

Conclusions

Steatosis is associated with liver stiffness and SWE may have the feasibility to be introduced as an assistive technology in grading steatosis for patients with NAFLD in absence of fibrosis.
Circadian disruption and sleep disorders in neurodegeneration
Authors: Shen Yun , Lv Qian-kun , Xie Wei-ye , Gong Si-yi , Zhuang Sheng , Liu Jun-yi , Mao Cheng-jie , Liu Chun-feng
Published: February 2023

Disruptions of circadian rhythms and sleep cycles are common among neurodegenerative diseases and can occur at multiple levels. Accumulating evidence reveals a bidirectional relationship between disruptions of circadian rhythms and sleep cycles and neurodegenerative diseases. Circadian disruption and sleep disorders aggravate neurodegeneration and neurodegenerative diseases can in turn disrupt circadian rhythms and sleep. Importantly, circadian disruption and various sleep disorders can increase the risk of neurodegenerative diseases. Thus, harnessing the circadian biology findings from preclinical and translational research in neurodegenerative diseases is of importance for reducing risk of neurodegeneration and improving symptoms and quality of life of individuals with neurodegenerative disorders via approaches that normalize circadian in the context of precision medicine. In this review, we discuss the implications of circadian disruption and sleep disorders in neurodegenerative diseases by summarizing evidence from both human and animal studies, focusing on the bidirectional links of sleep and circadian rhythms with prevalent forms of neurodegeneration. These findings provide valuable insights into the pathogenesis of neurodegenerative diseases and suggest a promising role of circadian-based interventions.
The diet rapidly and differentially affects the gut microbiota and host lipid mediators in a healthy population
Authors: Bourdeau-Julien Isabelle , Castonguay-Paradis Sophie , Rochefort Gabrielle , Perron Julie , Lamarche Benoît , Flamand Nicolas , Di Marzo Vincenzo , Veilleux Alain , Raymond Frédéric
Published: February 2023

Background

Bioactive lipids produced by human cells or by the gut microbiota might play an important role in health and disease. Dietary intakes are key determinants of the gut microbiota, its production of short-chain (SCFAs) and branched-chain fatty acids (BCFAs), and of the host endocannabinoidome signalling, which are all involved in metabolic diseases. This hypothesis-driven longitudinal fixed sequence nutritional study, realized in healthy participants, was designed to determine if a lead-in diet affects the host response to a short-term dietary intervention. Participants received a Mediterranean diet (MedDiet) for 3 days, a 13-day lead-in controlled diet reflecting the average Canadian dietary intake (CanDiet), and once again a MedDiet for 3 consecutive days. Fecal and blood samples were collected at the end of each dietary phase to evaluate alterations in gut microbiota composition and plasma levels of endocannabinoidome mediators, SCFAs, and BCFAs.

Results

We observed an immediate and reversible modulation of plasma endocannabinoidome mediators, BCFAs, and some SCFAs in response to both diets. BCFAs were more strongly reduced by the MedDiet when the latter was preceded by the lead-in CanDiet. The gut microbiota response was also immediate, but not all changes due to the CanDiet were reversible following a short dietary MedDiet intervention. Higher initial microbiome diversity was associated with reduced microbiota modulation after short-term dietary interventions. We also observed that BCFAs and 2-monoacylglycerols had many, but distinct, correlations with gut microbiota composition. Several taxa modulated by dietary intervention were previously associated to metabolic disorders, warranting the need to control for recent diet in observational association studies.

Conclusions

Our results indicate that lipid mediators involved in the communication between the gut microbiota and host metabolism exhibit a rapid response to dietary changes, which is also the case for some, but not all, microbiome taxa. The lead-in diet influenced the gut microbiome and BCFA, but not the endocannabinoidome, response to the MedDiet. A higher initial microbiome diversity favored the stability of the gut microbiota in response to dietary changes. This study highlights the importance of considering the previous diet in studies relating the gut microbiome with lipid signals involved in host metabolism.
Data-driven identification and classification of nonlinear aging patterns reveals the landscape of associations between DNA methylation and aging
Authors: Okada Daigo , Cheng Jian Hao , Zheng Cheng , Kumaki Tatsuro , Yamada Ryo
Published: February 2023

Background

Aging affects the incidence of diseases such as cancer and dementia, so the development of biomarkers for aging is an important research topic in medical science. While such biomarkers have been mainly identified based on the assumption of a linear relationship between phenotypic parameters, including molecular markers, and chronological age, numerous nonlinear changes between markers and aging have been identified. However, the overall landscape of the patterns in nonlinear changes that exist in aging is unknown.

Result

We propose a novel computational method, Data-driven Identification and Classification of Nonlinear Aging Patterns (DICNAP), that is based on functional data analysis to identify biomarkers for aging and potential patterns of change during aging in a data-driven manner. We applied the proposed method to large-scale, public DNA methylation data to explore the potential patterns of age-related changes in methylation intensity. The results showed that not only linear, but also nonlinear changes in DNA methylation patterns exist. A monotonous demethylation pattern during aging, with its rate decreasing at around age 60, was identified as the candidate stable nonlinear pattern. We also analyzed the age-related changes in methylation variability. The results showed that the variability of methylation intensity tends to increase with age at age-associated sites. The representative variability pattern is a monotonically increasing pattern that accelerates after middle age.

Conclusion

DICNAP was able to identify the potential patterns of the changes in the landscape of DNA methylation during aging. It contributes to an improvement in our theoretical understanding of the aging process.