bluuebunny/crossref_metadata_2025 huggingface dataset:
Leaves that walk and eggs that stick: comparative functional morphology and evolution of the adhesive system of leaf insect eggs (Phasmatodea: Phylliidae)
Authors: Büscher Thies H. , Bank Sarah , Cumming Royce T. , Gorb Stanislav N. , Bradler Sven
Published: May 2023

Phylliidae are herbivorous insects exhibiting impressive cryptic masquerade and are colloquially called “walking leaves”. They imitate angiosperm leaves and their eggs often resemble plant seeds structurally and in some cases functionally. Despite overall morphological similarity of adult Phylliidae, their eggs reveal a significant diversity in overall shape and exochorionic surface features. Previous studies have shown that the eggs of most Phylliidae possess a specialised attachment mechanism with hierarchical exochorionic fan-like structures (pinnae), which are mantled by a film of an adhesive secretion (glue). The folded pinnae and glue respond to water contact, with the fibrous pinnae expanding and the glue being capable of reversible liquefaction. In general, the eggs of phylliids appear to exhibit varying structures that were suggested to represent specific adaptations to the different environments the eggs are deposited in. Here, we investigated the diversity of phylliid eggs and the functional morphology of their exochorionic structure. Based on the examination of all phylliid taxa for which the eggs are known, we were able to characterise eleven different morphological types. We explored the adhesiveness of these different egg morphotypes and experimentally compared the attachment performance on a broad range of substrates with different surface roughness, surface chemistry and tested whether the adhesion is replicable after detachment in multiple cycles. Furthermore, we used molecular phylogenetic methods to reconstruct the evolutionary history of different egg types and their adhesive systems within this lineage, based on 53 phylliid taxa. Our results suggest that the egg morphology is congruent with the phylogenetic relationships within Phylliidae. The morphological differences are likely caused by adaptations to the specific environmental requirements for the particular clades, as the egg morphology has an influence on the performance regarding the surface roughness. Furthermore, we show that different pinnae and the adhesive glue evolved convergently in different species. While the evolution of the Phylliidae in general appears to be non-adaptive judging on the strong similarity of the adults and nymphs of most species, the eggs represent a stage with complex and rather diverse functional adaptations including mechanisms for both fixation and dispersal of the eggs.
Metabolites and gene expression in the myocardium of fasting rats in an acute hypoxic environment
Authors: Zhao Ruzhou , Wang Xiaobo , Zhou Xiang , Jiang Shuai , Zhang Lin , Yu Zhibin
Published: May 2023

With the rising demand for entry to extremely high altitudes (HAs), rapid adaptability to extremely hypoxic environments is a challenge that we need to explore. Fasting was used to evaluate acute hypoxia tolerance at HA and was proven to be an effective method for improving the survival rate at extreme HA. Our experiments also showed that fasting pretreatment for 72 h significantly increased the 24 h survival rate of rats at 7620 m from 10 to 85% and protected the myocardium cells of rats. Here, we compared the metabolites and gene expression in the myocardium of SD rats pretreated with fasting and nonfasting at normal altitude and extreme HA. Our findings demonstrated that the dynamic contents of detected differential metabolites (DMs) between different rat groups were consistent with the expression of differentially expressed genes (DEGs), and DM clusters also showed strong correlations with DEG clusters. DM clusters related to amino acids and lipids were significantly lower in the fasting groups, and the correlated DEG clusters were enriched in mitotic pathways, including CDK1, CDC7, NUF2, and MCM6, suggesting that fasting can attenuate mitotic processes in cardiac tissues and reduce the synthesis of amino acids and lipids. L-Glutamine-related metabolites were particularly low at extreme HA without pretreatment but were normal in the fasting groups. The DEGs in the cluster related to L-glutamine-related metabolites were enriched for T-cell receptor V(D)J recombination, the Hippo signaling pathway, the Wnt signaling pathway, the cGMP-PKG signaling pathway, and the mTOR signaling pathway and were significantly downregulated, indicating that the content of L-glutamine decreased at extreme HA, while fasting increased it to adapt to the environment. Moreover, abundant fatty acids were detected when rats were exposed to extreme HA without pretreatment. Our study revealed the fasting and hypoxic environment-related factors in SD rats and provided new insights into the genetic and molecular characteristics in the myocardium, which is critical to developing more potential rapid adaptation methods to extreme HA.
Combined transcriptomic and metabolomic analyses elucidate key salt-responsive biomarkers to regulate salt tolerance in cotton
Authors: Han Mingge , Cui Ruifeng , Wang Delong , Huang Hui , Rui Cun , Malik Waqar Afzal , Wang Jing , Zhang Hong , Xu Nan , Liu Xiaoyu , Lei Yuqian , Jiang Tiantian , Sun Liangqing , Ni Kesong , Fan Yapeng , Zhang Yuexin , Wang Junjuan , Chen Xiugui , Lu Xuke , Yin Zujun , Wang Shuai , Guo Lixue , Zhao Lanjie , Chen Chao , Ye Wuwei
Published: May 2023

Background

Cotton is an important industrial crop and a pioneer crop for saline-alkali land restoration. However, the molecular mechanism underlying the cotton response to salt is not completely understood.

Methods

Here, we used metabolome data and transcriptome data to analyze the salt tolerance regulatory network of cotton and metabolic biomarkers.

Results

In this study, cotton was stressed at 400 m M NaCl for 0 h, 3 h, 24 h and 48 h. NaCl interfered with cotton gene expression, altered metabolite contents and affected plant growth. Metabolome analysis showed that NaCl stress increased the contents of amino acids, sugars and ABA, decreased the amount of vitamin and terpenoids. K-means cluster analysis of differentially expressed genes showed that the continuously up-regulated genes were mainly enriched in metabolic pathways such as flavonoid biosynthesis and amino acid biosynthesis.

Conclusion

The four metabolites of cysteine (Cys), ABA(Abscisic acid), turanose, and isopentenyladenine-7-N-glucoside (IP7G) were consistently up-regulated under salt stress, which may indicate that they are potential candidates for cotton under salt stress biomarkers. Combined transcriptome and metabolome analysis revealed accumulation of cysteine, ABA, isopentenyladenine-7-N-glucoside and turanose were important for salt tolerance in cotton mechanism. These results will provide some metabolic insights and key metabolite biomarkers for salt stress tolerance, which may help to understanding of the metabolite response to salt stress in cotton and develop a foundation for cotton to grow better in saline soil.
Efficacy and safety of bifidobacterium quadruple viable tablets in the treatment of Helicobacter pylori-infected peptic ulcer or gastritis patients: a systematic review and meta-analysis
Authors: Jiang Xueliang , Xu Chunjin , Liu Bo , Chen Ping , Xu Qinchang , Zhang Lu
Published: May 2023

Background

To better understand the efficacy and safety of Bifidobacterium quadruple viable tablets in the treatment of helicobacter pylori (H. pylori)-infected peptic ulcer or gastritis patients.

Methods

A systematic review of the studies published to June 2022 was performed in English database PubMed, Embase, Chinese database CNKI, Wanfang. There were 17 studies were included in this systematic review and meta-analysis. The outcomes measured included H. pylori eradication rate, changes in clinical symptoms of epigastric pain scores, and the incidence of adverse reactions.

Results

The results of the fixed effect model showed that the eradication rate of H. pylori in the combination of Bifidobacterium quadruple viable bacteria tablets combined with bismuth-containing conventional quadruple therapy was greater than that of bismuth-containing conventional quadruple therapy, and the difference was statistically significant (OR = 3.73, 95%CI (2.79,5.00), Z = 2.78, P < 0.001; I2 = 0.0%, P > 0.999). The results of random effects model showed that the epigastric pain score of Bifidobacterium quadruple viable bacteria tablets combined with bismuth-containing conventional quadruple therapy was lower than that of bismuth-containing conventional quadruple therapy, and the difference was statistically significant (WMD=-0.70, 95%CI (-1.06,-0.34), Z = 3.82, P < 0.001; I2 = 96.7%, P < 0.001). The results of random effects model showed that the acid reflux score of Bifidobacterium quadruple viable bacteria tablets combined with bismuth-containing conventional quadruple therapy was lower than that of bismuth-containing conventional quadruple therapy, and the difference was statistically significant (WMD=-0.98, 95%CI (-1.70,-0.26), Z = 2.66, P < 0.001; I2 = 99.7%, P < 0.001).

Conclusions

The eradication rate of H. pylori by Bifidobacterium quadruple viable bacteria tablets combined with bismuth-containing quadruple therapy is better than that of bismuth-containing quadruple therapy. The improvement of clinical symptoms of patients is better than that of bismuth-containing quadruple therapy, and the incidence of adverse reactions is lower than that of bismuth-containing quadruple therapy. Bifidobacterium quadruple viable bacteria tablet combined with bismuth-containing quadruple therapy was effective and safe. It provides a new way to treat patients with H. pylori.
HIV rapid test performance among health facilities enrolled in HIV rapid test quality improvement initiative (RTQII) in Ethiopia
Authors: Yenealem Dereje , Kedir Shemsu , MekonnenWubie Asmare , Melese Daniel , Molalign Tamirat , Yemanebirhan Nebiyou , Mohammed Awad , Nurahmed Negash , Liknaw Wondimeneh , Lakew Abrham Kerealeme , Asrat Habtamu , Hailu Getnet , Kebede Addisu , Sisay Abay , Desta Kassu , Tsegaye Aster
Published: May 2023

Background

As the Human Immunodeficiency Virus (HIV) rapid testing services expanded to reach the global target that 95% of people living with the virus will know their status by 2030, ensuring the quality of those services becomes critical. This study was conducted to assess the performance of HIV Rapid testing at sites in health facilities that were enrolled in the Rapid Test Quality Improvement Initiative (RTQII) in Ethiopia.

Methods

Characterized HIV proficiency testing (PT) panels of Dried Tube Specimen (DTS) were prepared, verified, and distributed to testing sites from August to December 2019. In addition on-site evaluation of HIV testing sites (HTSs) was conducted using a checklist to assess testing conditions. For proficiency testing, the study included 159 HIV testing sites (HTSs) in 41 Health facilities (HFs) in five administrative regions and two city administrations. The collected data was analyzed by SPSS version 20 and chi-square test was applied to identify the association between acceptable performance and contributing factors. Testing sites with 100% PT score as well as conducting the test with adherence to the National HIV Testing Algorithm were considered acceptable.

Results

The overall acceptable performance (100% PT score with the correct algorithm followed) was found to be 62% while 12% scored 80% and 11% scored between 20 and 60%. The rest 15% were not considered as acceptable due to failure to adhere to the National HIV Testing Algorithm. Testing sites that participated in External Quality Assessment/Proficiency Testing schemes have shown better performance than those that did not participate with 70% and 56% performance respectively (p = 0.057).
Prediction of pathologic complete response after single-dose MR-guided partial breast irradiation in low-risk breast cancer patients: the ABLATIVE-2 trial—a study protocol
Authors: Civil Yasmin A. , Oei Arlene L. , Duvivier Katya M. , Bijker Nina , Meijnen Philip , Donkers Lorraine , Verheijen Sonja , van Kesteren Zdenko , Palacios Miguel A. , Schijf Laura J. , Barbé Ellis , Konings Inge R. H. M. , -van der Houven van Oordt C. Willemien Menke , Westhoff Paulien G. , Meijer Hanneke J. M. , Diepenhorst Gwen M. P. , Thijssen Victor , Mouliere Florent , Slotman Berend J. , van der Velde Susanne , van den Bongard H. J. G. Desirée
Published: May 2023

Background

Partial breast irradiation (PBI) is standard of care in low-risk breast cancer patients after breast-conserving surgery (BCS). Pre-operative PBI can result in tumor downstaging and more precise target definition possibly resulting in less treatment-related toxicity. This study aims to assess the pathologic complete response (pCR) rate one year after MR-guided single-dose pre-operative PBI in low-risk breast cancer patients.

Methods

The ABLATIVE-2 trial is a multicenter prospective single-arm trial using single-dose ablative PBI in low-risk breast cancer patients. Patients ≥ 50 years with non-lobular invasive breast cancer ≤ 2 cm, grade 1 or 2, estrogen receptor-positive, HER2-negative, and tumor-negative sentinel node procedure are eligible. A total of 100 patients will be enrolled. PBI treatment planning will be performed using a radiotherapy planning CT and -MRI in treatment position. The treatment delivery will take place on a conventional or MR-guided linear accelerator. The prescribed radiotherapy dose is a single dose of 20 Gy to the tumor, and 15 Gy to the 2 cm of breast tissue surrounding the tumor. Follow-up MRIs, scheduled at baseline, 2 weeks, 3, 6, 9, and 12 months after PBI, are combined with liquid biopsies to identify biomarkers for pCR prediction. BCS will be performed 12 months after radiotherapy or after 6 months, if MRI does not show a radiologic complete response. The primary endpoint is the pCR rate after PBI. Secondary endpoints are radiologic response, toxicity, quality of life, cosmetic outcome, patient distress, oncological outcomes, and the evaluation of biomarkers in liquid biopsies and tumor tissue. Patients will be followed up to 10 years after radiation therapy.

Discussion

This trial will investigate the pathological tumor response after pre-operative single-dose PBI after 12 months in patients with low-risk breast cancer. In comparison with previous trial outcomes, a longer interval between PBI and BCS of 12 months is expected to increase the pCR rate of 42% after 6–8 months. In addition, response monitoring using MRI and biomarkers will help to predict pCR. Accurate pCR prediction will allow omission of surgery in future patients.

Trial registration

The trial was registered prospectively on April 28th 2022 at clinicaltrials.gov (NCT05350722).
Evaluation of factors related to maternal anxiety during pregnancy among women referred to Tabriz primary care centers
Authors: Mahini Elmira , Hakimi Sevil , Shahrokhi Hassan , Salahi Behnaz , Baniadam Khatereh Olad , Ranjbar Fatemeh
Published: May 2023

Background

Maternal anxiety during pregnancy is sometimes considered a normal mechanism to overcome the mother’s mental preoccupation with having a child. However, stress and anxiety might become a medical condition, becoming so severe as to affect the mother’s mental health. Therefore, the present study aimed to investigate factors related to maternal anxiety during pregnancy in women referring to prenatal primary care centers in Tabriz.

Methods

The target population in the present cross-sectional study was the pregnant women referring to primary care centers affiliated with Tabriz University of Medical Sciences in 2018–2019 (n = 533). Sampling was carried out using the random cluster technique (separately for municipal centers). The data were collected using the study tools, including a questionnaire on demographic data, prenatal anxiety screening scale (PASS), and researcher-made questions on maternal anxiety during pregnancy.

Results

In the present study, 37.5% of pregnant women had anxiety. Of all the demographic and background variables, income (P = 0.015), a history of preterm delivery (P = 0.018), and unintended pregnancy (P = 0.022) were significantly related to anxiety. Of the variables of income, a history of preterm delivery, and unintended pregnancy in the regression model, the odds of anxiety were 41% lower in pregnant women with somewhat adequate income than those with inadequate income after correcting for other variables (P = 0.011). In addition, the variable of unintended pregnancy increased the odds of anxiety up to 49% after correcting for other variables (P = 0.023).

Conclusion

The present study showed that income and unintended pregnancy significantly affect maternal anxiety during pregnancy.

Trial registration

The protocol of the study was approved by the Ethics Committee of Tabriz University of Medical Sciences under the code (IR.TBZMED.REC.1398.161).
Clustering of lifestyle and health behaviours in Australian adolescents and associations with obesity, self-rated health and quality of life
Authors: Ahmad Kabir , Keramat Syed Afroz , Ormsby Gail M. , Kabir Enamul , Khanam Rasheda
Published: May 2023

Objective

The primary aim of this study was to identify clusters of lifestyle and health behaviours and explore their associations with health outcomes in a nationally representative sample of Australian adolescents.

Methods

The study participants were 3127 adolescents aged 14–15 years who participated in the eighth wave of the birth cohort of the Longitudinal Study of Australian Children (LSAC). A latent class analysis (LCA) was performed to identify clusters based on the behaviours of physical activity, alcohol consumption, smoking, diet, eating disorders, sleep problems and weight consciousness. Multinomial logistic regression models were fitted to the following health outcome variables: obesity, self-rated general health and pediatric health-related quality of life, to investigate their associations with LCA clusters.

Results

Based on the prevalence of health behaviour related characteristics, LCA identified gender based distinct clusters of adolescents with certain outward characteristics. There were five clusters for male and four clusters for female participants which are named as: healthy lifestyle, temperate, mixed lifestyle, multiple risk factors, and physically inactive (male only). Adolescents in the healthy lifestyle and temperate clusters reported low and moderately active health risk behaviours, for example, low physical activity, inadequate sleep and so on, while these behaviours were prevailing higher among adolescents of other clusters. Compared to adolescents of healthy lifestyle clusters, male members of physically inactive (OR = 3.87, 95% CI: 1.12 – 13.33) or mixed lifestyle (OR = 5.57, 95% CI: 3.15 – 9.84) clusters were over three to five times more likely to have obesity; while for female adolescents, members of only multiple risk factors clusters (OR = 3.61, 95% CI: 2.00 – 6.51) were over three time more likely to have obesity compared to their counterpart of healthy lifestyle clusters. Adolescents of physically inactive (b = -9.00 for male only), mixed lifestyle (b = -2.77 for male; b = -6.72 for female) or multiple risk factors clusters (b = -6.49 for male; b = -6.59 for female) had a stronger negative association with health-related quality of life scores compared to adolescents of healthy lifestyle clusters.

Conclusion

The study offers novel insights into latent class classification through the utilisation of different lifestyles and health-related behaviours of adolescents to identify characteristics of vulnerable groups concerning obesity, general health status and quality of life. This classification strategy may help health policy makers to target vulnerable groups and develop appropriate interventions.
The effect of double W tension-reduced suture technique on the abdominal scars following the da Vinci robot-assisted gastrectomy for severely obese patients
Authors: Chen Wanying , Jiang Tao , Zhong Ziming , Wang Xiaodong , Cao Yang , Wu Yujing , Gai Haiyang , Zhang Lianbo , Yu Yang
Published: May 2023

Objective

To analyze the effect of a new type of tension-reduced suture named “double W tension-reduced suture technique” on the abdominal scars following the da Vinci robot-assisted gastrectomy for severely obese patients.

Methods

40 abdominal incisions following the da Vinci robot-assisted gastrectomy on severely obese patients from September 1st, 2021 to March 1st, 2022 were comprised in the study. 20 incisions were closed by the conventional full-thickness surgical suture as the control group, and 20 incisions were sewn up by double W tension-reduced suture as the double W group. The scars were assessed at the 1-month follow-up visit using the Vancouver scar scale (VSS), ultrasound and patient satisfaction. Meanwhile, digital photographs of scars were taken as well.

Results

The VSS score was 6.80 ± 2.16 in the control group, while that of the double W group was 2.60 ± 1.89. The difference between groups was significant. Digital photographs showed that the scar color was not only light and close to the skin color, but also flat and soft in the double W group. Ultrasound showed that the fibers of subcutaneous tissue in the double W group were arranged neatly, the ultrasonic signal intensity was relatively uniform, and the tunnel was small without obvious lacunae. More patients were satisfied and very satisfied with scars in the double W group.

Conclusion

Double W tension-reduced suture technique could significantly improve the appearance and reduce comorbidities of scars following the da Vinci robot-assisted gastrectomy for severely obese patients.
Comparison of the learning curve of intraoral scanning with two different intraoral scanners based on scanning time
Authors: Róth Ivett , Hermann Péter , Vitai Viktória , Joós-Kovács Gellért Levente , Géczi Zoltán , Borbély Judit
Published: May 2023

Background

The appearance of intraoral scanners (IOSs) in dental offices was an important milestones for the digital innovations in dentistry. Knowing the learning curve for intraoral scanning is crucial, because it can serve as a guideline for clinicians before buying a new IOS. The aim of the present in vivo study was to determine the learning curve required by dental students for intraoral scanning with the 3Shape Trios 4 IOS and the CEREC Primescan IOS, based on scanning time.

Methods

A total of 20 dental students with no previous experience in intraoral scanning participated in the present study. 10 students scanned with Trios 4® IOS (TRI) and 10 students took digital impressions with Primescan® IOS (CER). Every student created 15 digital impressions from patients. Prior to taking the impressions, theoretical and practical education was provided. The total scanning time included the upper and lower arches as well as bite registration, for which average values were calculated. Statistical analysis was performed using the Stata package with a mixed-effects generalized least squares regression models.

Results

The average total scanning times were the following: TRI – 205 s for the 1st impression, 133.6 s for the 15th, CER – 289.8 s for the 1st impression, 147 s for the 15th. The model-based estimate of the difference between the two in case of TRI was 57.5 s, and in CER was 144.2 s which is a highly significant improvement in both cases (P < 0.0001). The slope of the scanning time vs. learning phase curve gradually approached flatness, and maintained a plateau: TRI – from the 11th measurement and CER – from the 14th measurement onward.

Conclusions

Given the limitations of the present study, we found difference between the learning curve of scanner types which are operate various principle of imaging. In case of the TRI fewer digital impressions (11 repeating) were sufficient to reach the average scanning time of an experienced user than using CER (14 repeating).

Trial registration

The permission for this study was given by the University Ethics Committee of Semmelweis University (SE RKEB number: 184/2022).
Effects of spinal anaesthesia and intravenous general anaesthesia on the absorption of normal salinein patients undergoing hysteroscopic endometrial resection: an observational study
Authors: Fu Wuchang , Li Xue , Xu Hongchun , Zhao Ting , Wang Fangjun
Published: May 2023

Introduction

The absorption of uterine distention fluid during hysteroscopic endometrial resection can cause volumeoverload, which can lead to coagulation dysfunction, acute left heart failure and pulmonary oedema in patients. The effects of spinal anaesthesia and intravenous general anaesthesia on the absorption of normal saline as uterine distention fluid during hysteroscopic surgery remain unclear. The aim of this clinical trial was toobserve the effects of spinal anaesthesia and intravenous general anaesthesia on the absorption of normal saline in patients undergoing hysteroscopic endometrial resection.

Methods

A total of 126 patients undergoing elective hysteroscopic endometrial resection were divided into a spinal anaesthesia group (s group) and a propofol-fentanyl intravenous anaesthesia group (PF group), with 63 cases in each group, and both groups were divided into a short-term group (S1 group and PF1 group) and a long-term group (S2 group and PF2 group) according to the operation time. The primary outcome was the absorption of normal saline, and the secondary outcomes included the perioperative SBP, DBP, HR and SpO2 and postoperative haematocrit values, and the incidence of postoperative complications.

Results

The volume of saline absorbed was significantly increased in the S2 and PF2 groups compared with the S1 and PF1 groups (P < 0.001). There was a significant positive correlation between the amount of normal saline absorbed and the operation time (r = 0.895, P < 0.001). The postoperative haematocrit value was slightly lower than that before the operation in all four groups (P < 0.05), and there were no differences in the incidences of urinary retention, sinus bradycardia or hypotension between groups (P > 0.05).

Conclusions

There was no difference in the effects of spinal anaesthesia and intravenous general anaesthesia on the absorption of normal saline during hysteroscopic endometrial resection, and the absorption of normal saline increased accordingly with the extension of operation time.
Supervision of redeployed surgical trainees during the COVID-19 pandemic: what have we learnt and how can we improve?
Authors: Wright Esther V , Haden Nicholas D , Dalrymple Kirsten
Published: May 2023

Objective

When cases of patients presenting with Coronavirus Disease 2019 (COVID-19) overwhelmed existing services in the United Kingdom (UK), surgical trainees were redeployed to assist frontline efforts. This project characterises the effects of redeployment on the supervision of these trainees. The resulting generation of practical recommendations could be implemented for future crises.

Design

A qualitative approach was utilised, comprised of seven phenomenological interviews with surgical and intensive care consultants, as well as redeployed surgical trainees. Interview recordings were transcribed and subsequently analysed using Thematic Analysis.

Setting

The project utilised participants currently in surgical training within the London deanery across a variety of surgical specialties representing several UK National Health Service (NHS) Trusts.

Participants

Three types of participants were interviewed. Four interviews were conducted with redeployed surgical trainees, across all stages of training, in full time employment who were redeployed for two weeks or more. One interview was conducted with an educational supervisor of multiple redeployed trainees. The third group comprised two consultant intensivists who supervised redeployed trainees within their respective departments.

Results

Four themes were developed: ‘Responding to an unforeseen crisis’, ‘Maintaining surgical identity and culture; A fish out of water?’, ‘Trainee supervision and support’ and ‘Preparation and sequelae’. Participants described a sense of obligation to the pandemic effort. Many described a significant interruption to training, however communication of this to surgical supervisors was suboptimal with minimal mitigation. Supervisors on the frontline were challenged by the assessment of trainee competence and acceptance into a new community of practice. Both trainees and supervisors described the management of uncertainty, advocating for the use of reflective practice to ensure preparation for the future.

Conclusion

This project presents an insight into several potentially long-lasting effects on surgical training. The recommendations generated may be applicable to trainees returning to work from time out of training, increasing the utility of this work.
Cancer patients as parents: implementation of a cross sector service for families with adolescent and young adult children
Authors: Skrabal Ross X. , McDonald F.E.J. , Konings S. , Schiena E. , Phipps-Nelson J. , Hodgson F. , Patterson P.
Published: May 2023

Background

Cancer patients who are parents show concerns about their ability to parent following diagnosis, and their adolescent and young adult (AYA) children have a need for improved cancer communication within the family. However, psychosocial support for families affected by parental cancer is not routinely available. This study explores the implementation of the Parent Support Worker (PSW) role, as part of a new cross sector model of care to support parent patients, their partners, and AYA children.

Methods

Two PSWs, social workers and healthcare staff (n = 26) from three hospitals participated in audio-recorded, semi-structured interviews about implementation of the PSW role. Template Analysis and Normalization Process Theory were used to analyze the interviews. Data on PSW service activity and referrals of AYA to support from a community organization were analyzed using descriptive statistics.

Results

Eleven themes categorized into enablers and barriers of implementation were identified. Regarding acceptability of the role, three enablers (social workers’ understanding of the PSW role increasing, easy and prompt access of staff and parent patients to PSWs, satisfaction with the PSW role) and one barrier (communication related confusion and frustration about the PSW role) were identified. Additionally, three enablers (the PSW role fills gaps in parenting-focused support and continuity of care, the PSW role alleviates social workers’ workload, negotiation helped to define responsibilities) and one barrier (fear of social work roles to be overtaken by PSWs) for appropriateness of the role were found. Finally, two enablers of feasibility of the role (PSWs and social workers co-managing the work, higher confidence from hospital staff to talk about children in the family) and one barrier (lack of systematic identification and referral processes) were identified. Across hospitals, the number of referrals of AYA children to the community organization increased between 2.7 and 12 times nine months post-introduction of the service.

Conclusions

Established in response to identified gaps in oncology care for parents with cancer, their partners and AYA children, a novel cross-sector model of care was acceptable, appropriate, and feasible. Barriers and enablers to implementation identified in this study need to be considered when designing and implementing similar services.
Factors related to the waiting time for scheduling an oral biopsy in Brazil: a multilevel analysis
Authors: De-Carli Alessandro Diogo , da Cunha Amanda Ramos , do Amaral-Silva Gleyson Kleber , Vasconcelos Jader , dos Santos Mara Lisiane de Moraes , Probst Livia Fernandes
Published: May 2023

Background

Timely diagnosis of oral cancers is critical, and performing biopsies of oral lesions with suspected malignancy is a crucial step in achieving this goal. The waiting time for the diagnosis may be related to the progression and prognosis of malignant neoplasms.

Objective

The aim of this observational, cross-sectional, national-level study was to identify the factors associated with the waiting time for scheduling an oral biopsy, based on the identification of its need.

Methods

We used secondary data from the Brazilian public health system, obtained from the 2nd cycle of the National Program to Improve Access and Quality of Dental Specialty Centers (PMAQ-CEO). The study outcome was the waiting time for scheduling an oral biopsy, starting from the identification of the need for the exam. We analyzed individual and contextual variables using multilevel statistical analysis.

Results

In 51.8% of DSC the waiting time for scheduling a biopsy was non-immediate; in 58.1% of CEOs, the sum of the weekly workload of dentists working in the Stomatology specialty is up to 20 h per week; in terms of coverage, 67.1% of the CEOs have only municipal coverage and 34.0% are references for up to 12 oral health teams in primary health care; only the coverage variable remained significant in the multivariate model (p < 0.05). Of the contextual variables, none of the variables remained significant (p > 0.05). When these were analyzed together, only the coverage remained significant (p < 0.05);

Conclusion

Our analysis indicates that the waiting time for scheduling an oral biopsy is longer in CEOs that cover only one municipality and is not related to contextual factors.
Integrated bulk and single-cell RNA-sequencing reveals SPOCK2 as a novel biomarker gene in the development of congenital pulmonary airway malformation
Authors: Tan Zheng , Li Fengxia , Chen Qiang , Chen Hongyu , Xue Ziru , Zhang Jian , Gao Yue , Liang Liang , Huang Ting , Zhang Shouhua , Li Jianhua , Shu Qiang , Yu Lan
Published: May 2023

Background

Congenital pulmonary airway malformation (CPAM) is the most frequent pulmonary developmental malformation and the pathophysiology remains poorly understood. This study aimed to identify the characteristic gene expression patterns and the marker genes essential to CPAM.

Methods

Tissues from the cystic area displaying CPAM and the area of normal appearance were obtained during surgery. Bulk RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq) were performed for integrating analysis. Iterative weighted gene correlation network analysis (iWGCNA) was used to identify specifically expressed genes to CPAM.

Results

In total, 2074 genes were significantly differentially expressed between the CPAM and control areas. Of these differentially expressed genes (DEGs), 1675 genes were up-regulated and 399 genes were down-regulated. Gene ontology analysis revealed these DEGs were specifically enriched in ciliated epithelium and involved in immune response. We also identified several CPAM-related modules by iWGCNA, among them, P15_I4_M3 module was the most influential module for distinguishing CPAMs from controls. By combining the analysis of the expression dataset from RNA-seq and scRNA-seq, SPOCK2, STX11, and ZNF331 were highlighted in CPAM.

Conclusions

Through our analysis of expression datasets from both scRNA-seq and bulk RNA-seq of tissues obtained from patients with CPAM, we identified the characteristic gene expression patterns associated with the condition. Our findings suggest that SPOCK2 could be a potential biomarker gene for the diagnosis and therapeutic target in the development of CPAM, whereas STX11 and ZNF331 might serve as prognostic markers for this condition. Further investigations with larger samples and function studies are necessary to confirm the involvement of these genes in CPAM.
Implementation of ask-advise-connect for smoking cessation in Dutch general practice during the COVID-19 pandemic: a mixed-methods evaluation using the CFIR framework
Authors: van Westen-Lagerweij Naomi A. , Willemsen Marc C. , Croes Esther A. , Chavannes Niels H. , Meijer Eline
Published: May 2023

Background

The Ask-Advise-Connect (AAC) approach can help primary care providers to increase the number of people who attempt to quit smoking and enrol into cessation counselling. We implemented AAC in Dutch general practice during the COVID-19 pandemic. In this study we describe how AAC was received in Dutch general practice and assess which factors played a role in the implementation.

Methods

A mixed-methods approach was used to evaluate the implementation of AAC. Implementation took place between late 2020 and early 2022 among 106 Dutch primary care providers (general practitioners (GPs), practice nurses and doctor’s assistants). Quantitative and qualitative data were collected through four online questionnaires. A descriptive analysis was conducted on the quantitative data. The qualitative data (consisting of answers to open-ended questions) were inductively analysed using axial codes. The Consolidated Framework for Implementation Research was used to structure and interpret findings.

Results

During the study, most participants felt motivated (84–92%) and able (80–94%) to apply AAC. At the end of the study, most participants reported that the AAC approach is easy to apply (89%) and provides advantages (74%). Routine implementation of the approach was, however, experienced to be difficult. More GPs (30–48%) experienced barriers in the implementation compared to practice nurses and doctor’s assistants (7–9%). The qualitative analysis showed that especially external factors, such as a lack of time or priority to discuss smoking due to the COVID-19 pandemic, negatively influenced implementation of AAC.

Conclusions

Although AAC was mostly positively received in Dutch general practice, implementation turned out to be challenging, especially for GPs. Lack of time to discuss smoking was a major barrier in the implementation. Future efforts should focus on providing additional implementation support to GPs, for example with the use of e-health.
Linear accelerator-based stereotactic radiotherapy for brain metastases, including multiple and large lesions, carries a low incidence of acute toxicities: a retrospective analysis
Authors: Ikawa Toshiki , Kanayama Naoyuki , Arita Hideyuki , Ohira Shingo , Takano Koji , Hirata Takero , Morimoto Masahiro , Teshima Teruki , Konishi Koji
Published: May 2023

Background

Data on acute toxicities after stereotactic radiotherapy (SRT) for brain metastases, including multiple and large lesions, are lacking. We aimed to evaluate the incidence and nature of toxicities immediately after SRT using a linear accelerator.

Methods

This retrospective study reviewed the medical records of 315 patients with brain metastases treated with SRT at our institution between May 2019 and February 2022. In total, 439 SRT sessions were performed for 2161 brain metastases. The outcome of interest was immediate side effects (ISEs), defined as new or worsening symptoms occurring during SRT or within 14 days after the end of SRT.

Results

Grade ≥ 2 and ≥ 3 ISEs occurred in 16 (3.6%) and 7 (1.6%) cases, respectively. Among 63 treatments for 10 or more lesions (range: 10–40), 1 (1.6%) ISE occurred. Among 22 treatments for lesions with a maximum tumor volume of > 10 cc, 2 (9.1%) ISEs occurred. Grade ≥ 3 ISEs included 1, 4, 1, and 1 cases of grade 3 nausea, grade 3 new-onset partial and generalized seizures, grade 3 obstructive hydrocephalus, and grade 5 intracranial hemorrhage, respectively. ISEs were more common in patients with a larger maximum tumor volume, primary sites other than lung and breast cancer, and pre-treatment neurological symptoms.

Conclusion

SRT using a linear accelerator for brain metastases, including multiple and large lesions, is safe, with a low incidence of ISEs. Serious complications immediately after SRT are rare but possible; therefore, careful follow-up is necessary after treatment initiation.
Cyp4a12-mediated retinol metabolism in stellate cells is the antihepatic fibrosis mechanism of the Chinese medicine Fuzheng Huayu recipe
Authors: Ping Da-bing , Sun Xin , Peng Yuan , Liu Cheng-hai
Published: May 2023

Background

Hepatic stellate cells (HSCs), which contain multiple retinol-containing lipid droplets, are important profibrotic cells in liver fibrosis. Under Cyp4a12a/b oxidation, HSC activation was accompanied by the downregulation of genes involved in retinol metabolism, inducing RAE-1 production. By eliminating activated HSCs, NK cells expressing the activating receptor NKG2D are recruited to alleviate fibrosis. FZHY was found to significantly reduce the severity of liver fibrosis by inhibiting the activation and proliferation of HSCs. The molecular processes that govern retinol metabolism, on the other hand, are largely unexplored. This study focused on the regulation of Cyp4a12a/b by FZHY to elucidate the antifibrotic molecular mechanisms underlying the effect of FZHY on retinol metabolism.

Methods

To investigate mechanisms and altered pathways of FZHY against carbon tetrachloride (CCl4)-induced liver fibrosis based on transcriptomics data. Bioinformatics analysis was used to screen its pharmacological targets. The predicted targets were confirmed by a series of in vitro and in vivo experiments, including mass spectrometry, in situ hybridization, immunofluorescence assays and real-time PCR. Then, the results were further characterized by recombinant adenovirus vectors that were constructed and transfected into the cultured primary HSCs.

Results

Transcriptomics revealed that Cyp4a12a/b is nearly completely lost in liver fibrosis, and these effects might be partially reversed by FZHY therapy recovery. In vitro and in vivo studies indicated that Cyp4a12a/b deletion disrupted retinol metabolism and lowered Rae-1 expression. Activated HSCs successfully escape recognition and elimination by natural killer (NK) cells as a result of reduced Rae-1. Notablely, we discovered that FZHY may restore the Cyp4a12a/b capability, allowing the recovery of the cytotoxic function of NK cells against HSCs, and thereby reducing hepatic fibrosis by suppressing HSC activation.

Conclusion

Our findings revealed a new role for Cyp4a in retinol metabolism in the development of hepatic fibrosis, and they highlight Cyp4a12/Rae-1 signals as possible therapeutic targets for antifibrotic medicines.
Intratracheal budesonide mixed with surfactant to increase survival free of bronchopulmonary dysplasia in extremely preterm infants: study protocol for the international, multicenter, randomized PLUSS trial
Authors: Manley Brett J. , Kamlin C. Omar F. , Donath Susan , Huang Li , Birch Pita , Cheong Jeanie L. Y. , Dargaville Peter A. , Dawson Jennifer A. , Doyle Lex W. , Jacobs Susan E. , Wilson Rodney , Davis Peter G. , McKinlay Christopher J. D.
Published: May 2023

Background

Bronchopulmonary dysplasia (BPD), an inflammatory-mediated chronic lung disease, is common in extremely preterm infants born before 28 weeks’ gestation and is associated with an increased risk of adverse neurodevelopmental and respiratory outcomes in childhood. Effective and safe prophylactic therapies for BPD are urgently required. Systemic corticosteroids reduce rates of BPD in the short-term but are associated with poorer neurodevelopmental outcomes if given to ventilated infants in the first week after birth. Intratracheal administration of corticosteroid admixed with exogenous surfactant could overcome these concerns by minimizing systemic sequelae. Several small, randomized trials have found intratracheal budesonide in a surfactant vehicle to be a promising therapy to increase survival free of BPD.

Methods

An international, multicenter, double-blinded, randomized trial of intratracheal budesonide (a corticosteroid) mixed with surfactant for extremely preterm infants to increase survival free of BPD at 36 weeks’ postmenstrual age (PMA; primary outcome). Extremely preterm infants aged < 48 h after birth are eligible if: (1) they are mechanically ventilated, or (2) they are receiving non-invasive respiratory support and there is a clinical decision to treat with surfactant. The intervention is budesonide (0.25 mg/kg) mixed with poractant alfa (200 mg/kg first intervention, 100 mg/kg if second intervention), administered intratracheally via an endotracheal tube or thin catheter. The comparator is poractant alfa alone (at the same doses). Secondary outcomes include the components of the primary outcome (death, BPD prior to or at 36 weeks’ PMA), potential systemic side effects of corticosteroids, cost-effectiveness, early childhood health until 2 years of age, and neurodevelopmental outcomes at 2 years of age (corrected for prematurity).

Discussion

Combining budesonide with surfactant for intratracheal administration is a simple intervention that may reduce BPD in extremely preterm infants and translate into health benefits in later childhood. The PLUSS trial is powered for the primary outcome and will address gaps in the evidence due to its pragmatic and inclusive design, targeting all extremely preterm infants regardless of their initial mode of respiratory support. Should intratracheal budesonide mixed with surfactant increase survival free of BPD, without severe adverse effects, this readily available intervention could be introduced immediately into clinical practice.

Trial registration

Australian New Zealand Clinical Trials Registry (https://www.anzctr.org.au), ACTRN12617000322336. First registered on 28th February 2017.
Association of gut microbial dysbiosis with disease severity, response to therapy and disease outcomes in Indian patients with COVID-19
Authors: Talukdar Daizee , Bandopadhyay Purbita , Ray Yogiraj , Paul Shekhar Ranjan , Sarif Jafar , D’Rozario Ranit , Lahiri Abhishake , Das Santanu , Bhowmick Debaleena , Chatterjee Shilpak , Das Bhabatosh , Ganguly Dipyaman
Published: May 2023

Background

Severe coronavirus disease 2019 (COVID-19) is associated with systemic hyper-inflammation. An adaptive interaction between gut microbiota and host immune systems is important for intestinal homeostasis and systemic immune regulation. The association of gut microbial composition and functions with COVID-19 disease severity is sparse, especially in India. We analysed faecal microbial diversity and abundances in a cohort of Indian COVID-19 patients to identify key signatures in the gut microbial ecology in patients with severe COVID-19 disease as well as in response to different therapies. The composition of the gut microbiome was characterized using 16Sr RNA gene sequences of genomic DNA extracted from faecal samples of 52 COVID-19 patients. Metabolic pathways across the groups were predicted using PICRUSt2. All statistical analyses were done using Vegan in the R environment. Plasma cytokine abundance at recruitment was measured in a multiplex assay.

Results

The gut microbiome composition of mild and severe patients was found to be significantly different. Immunomodulatory commensals, viz. Lachnospiraceae family members and Bifidobacteria producing butyrate and short-chain fatty acids (SCFAs), were under represented in patients with severe COVID-19, with an increased abundance of opportunistic pathogens like Eggerthella. The higher abundance of Lachnoclostridium in severe disease was reduced in response to convalescent plasma therapy. Specific microbial genera showed distinctive trends in enriched metabolic pathways, strong correlations with blood plasma cytokine levels, and associative link to disease outcomes.

Conclusion

Our study indicates that, along with SARS-CoV-2, a dysbiotic gut microbial community may also play an important role in COVID-19 severity through modulation of host immune responses.