bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Piston Number on Churning Losses in Axial Piston Pumps
Authors: Li Ying , Chen Xing , Luo Hao , Zhang Junhui , Zhang Jin
Published: June 2022

Raising the rotational speed of an axial piston pump is useful for improving its power density; however, the churning losses of the piston increase significantly with increasing speed, and this reduces the performance and efficiency of the axial piston pump. Currently, there has been some research on the churning losses of pistons; however, it has rarely been analyzed from the perspective of the piston number. To improve the performance and efficiency of the axial piston pump, a computational fluid dynamics (CFD) simulation model of the churning loss was established, and the effect of piston number on the churning loss was studied in detail. The simulation analysis results revealed that the churning losses initially increased as the number of pistons increased; however, when the number of pistons increased from six to nine, the torque of the churning losses decreased because of the hydrodynamic shadowing effect. In addition, in the analysis of cavitation results, it was determined that the cavitation area of the axial piston pump was mainly concentrated around the piston, and the cavitation became increasingly severe as the speed increased. By comparing the simulation results with and without the cavitation model, it was observed that the cavitation phenomenon is beneficial for the reduction of churning losses. In this study, a piston churning loss test rig that can eliminate other friction losses was established to verify the accuracy of the simulation results. A comparative analysis indicated that the simulation results were consistent with the actual situation. In addition, this study also conducted a simulation study on seven and nine piston pumps with the same displacement. The simulation results revealed that churning losses of the seven pistons were generally greater than those of the nine pistons under the same displacement. In addition, regarding the same piston number and displacement, reducing the pitch circle radius of piston bores is effective in reducing the churning loss. This research analyzes the effect of piston number on the churning loss, which has certain guiding significance for the structural design and model selection of axial piston pumps.
Contribution of tetrodotoxin-resistant persistent Na+ currents to the excitability of C-type dural afferent neurons in rats
Authors: Nakamura Michiko , Jang Il-Sung
Published: June 2022

Background

Growing evidence supports the important role of persistent sodium currents (INaP) in the neuronal excitability of various central neurons. However, the role of tetrodotoxin-resistant (TTX-R) Na+ channel-mediated INaP in the neuronal excitability of nociceptive neurons remains poorly understood.

Methods

We investigated the functional role of TTX-R INaP in the excitability of C-type nociceptive dural afferent neurons, which was identified using a fluorescent dye, 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchloride (DiI), and a whole-cell patch-clamp technique.

Results

TTX-R INaP were found in most DiI-positive neurons, but their density was proportional to neuronal size. Although the voltage dependence of TTX-R Na+ channels did not differ among DiI-positive neurons, the extent of the onset of slow inactivation, recovery from inactivation, and use-dependent inhibition of these channels was highly correlated with neuronal size and, to a great extent, the density of TTX-R INaP. In the presence of TTX, treatment with a specific INaP inhibitor, riluzole, substantially decreased the number of action potentials generated by depolarizing current injection, suggesting that TTX-R INaP are related to the excitability of dural afferent neurons. In animals treated chronically with inflammatory mediators, the density of TTX-R INaP was significantly increased, and it was difficult to inactivate TTX-R Na+ channels.

Conclusions

TTX-R INaP apparently contributes to the differential properties of TTX-R Na+ channels and neuronal excitability. Consequently, the selective modulation of TTX-R INaP could be, at least in part, a new approach for the treatment of migraine headaches.
The role of epigenetic modifications in drug resistance and treatment of breast cancer
Authors: Karami Fath Mohsen , Azargoonjahromi Ali , Kiani Arash , Jalalifar Fateme , Osati Parisa , Akbari Oryani Mahsa , Shakeri Fateh , Nasirzadeh Farhad , Khalesi Behman , Nabi-Afjadi Mohsen , Zalpoor Hamidreza , Mard-Soltani Maysam , Payandeh Zahra
Published: June 2022

Background

Breast cancer is defined as a biological and molecular heterogeneous disorder that originates from breast cells. Genetic predisposition is the most important factor giving rise to this malignancy. The most notable mutations in breast cancer occur in the BRCA1 and BRCA2 genes. Owing to disease heterogeneity, lack of therapeutic target, anti-cancer drug resistance, residual disease, and recurrence, researchers are faced with challenges in developing strategies to treat patients with breast cancer.

Results

It has recently been reported that epigenetic processes such as DNA methylation and histone modification, as well as microRNAs (miRNAs), have potently contributed to the pathophysiology, diagnosis, and treatment of breast cancer. These observations have persuaded researchers to move their therapeutic approaches beyond the genetic framework toward the epigenetic concept.

Conclusion

Herein we discuss the molecular and epigenetic mechanisms underlying breast cancer progression and resistance as well as various aspects of epigenetic-based therapies as monotherapy and combined with immunotherapy.
HIOPP-6 – a pilot study on the evaluation of an electronic tool to assess and reduce the complexity of drug treatment considering patients’ views
Authors: Wurmbach Viktoria S. , Schmidt Steffen J. , Lampert Anette , Bernard Simone , Meid Andreas D. , Frick Eduard , Metzner Michael , Wilm Stefan , Mortsiefer Achim , Bücker Bettina , Altiner Attila , Sparenberg Lisa , Szecsenyi Joachim , Peters-Klimm Frank , Kaufmann-Kolle Petra , Thürmann Petra A. , Seidling Hanna M. , Haefeli Walter E.
Published: June 2022

Background

A complex drug treatment might pose a barrier to safe and reliable drug administration for patients. Therefore, a novel tool automatically analyzes structured medication data for factors possibly contributing to complexity and subsequently personalizes the results by evaluating the relevance of each identified factor for the patient by means of key questions. Hence, tailor-made optimization measures can be proposed.

Methods

In this controlled, prospective, exploratory trial the tool was evaluated with nine general practitioners (GP) in three study groups: In the two intervention groups the tool was applied in a version with (GI_with) and a version without (GI_without) integrated key questions for the personalization of the analysis, while the control group (GC) did not use any tools (routine care). Four to eight weeks after application of the tool, the benefits of the optimization measures to reduce or mitigate complexity of drug treatment were evaluated from the patient perspective.

Results

A total of 126 patients regularly using more than five drugs could be included for analysis. GP suggested 117 optimization measures in GI_with, 83 in GI_without, and 2 in GC. Patients in GI_with were more likely to rate an optimization measure as helpful than patients in GI_without (IRR: 3.5; 95% CI: 1.2—10.3). Thereby, the number of optimization measures recommended by the GP had no significant influence (P = 0.167).

Conclusions

The study suggests that an automated analysis considering patient perspectives results in more helpful optimization measures than an automated analysis alone – a result which should be further assessed in confirmatory studies.

Trial registration

The trial was registered retrospectively at the German Clinical Trials register under DRKS-ID DRKS00025257 (17/05/2021).
Understanding the processes behind the decisions – GPs and complex multimorbidity decision making
Authors: Hughes Lloyd D.
Published: June 2022

Complex multimorbidity, defined either as three or more chronic conditions affecting three or more different body systems or by the patients General Practitioner (GPs), is associated with various adverse outcomes. Understanding how GPs reach decisions for this complex group of patients is currently under-researched, with potential implications for health systems and service delivery. Schuttner and colleagues, through a qualitative approach, reported that internal factors of individuals (decisions tailored to patients; Primary Care Physician (PCP) consultation style; care planning towards an agreed goal of care), external factors within the environment or context of encounter (patient access to healthcare; organizational structures acting as barriers), and relationship-based factors (collaborative care planning; decisions within a dynamic patient clinician relationship) all influence care planning decisions. There are other important findings which have broader relevance to the literature such as the ongoing separation of physical and mental health which persist even within integrated care systems, GPs continue to prioritize continuity of care and that organizational barriers are reported as factors in clinician decision-making for patients. More broadly, the work has proved valuable in extending previously reported findings surrounding care coordination, and limitation of current guidelines for patients with complex multimorbidity. Work-load in general practice is increasing due to an ageing population, increasing prevalence of multimorbidity and polypharmacy, and transfer of clinical activities from secondary to primary care. The future for GPs is more complexity in the clinic room, understanding how GPs make decisions and how this can be supported is crucial for the sustainability for general practice.
Colonic bacterial diversity and dysbiosis in active microscopic colitis as compared to chronic diarrhoea and healthy controls: effect of polyethylene glycol after bowel lavage for colonoscopy
Authors: Batista Lissette , Robles Virginia , Manichanh Chaysavanh , Ruiz Laura , Guagnozzi Danila , Pinsach Ferran , Guarner Francisco , Fernández-Bañares Fernando
Published: June 2022

Background

Most microbiota studies in microscopic colitis patients are performed after diagnostic colonoscopy without considering the potential effect of colonic lavage. Patients may achieve clinical remission after colonoscopy and it is unknown whether lavage-induced changes play a role.

Aim

To assess the effect of polyethylene glycol (PEG) colonic lavage on clinical remission rate, microbial diversity, microbial dysbiosis index and specific microbial changes in patients with active microscopic colitis as compared to other diarrhoeal diseases and healthy controls.

Methods

Fifty-five consecutive patients presenting chronic watery diarrhoea and 12 healthy controls were included. Faecal samples were collected three days before and 30 days after PEG in patients and controls for microbiome analysis.

Results

Clinical remission was observed in 53% of microscopic colitis patients, and in 32% of non-microscopic colitis patients (p = 0.16). Considering patients with persisting diarrhoea after colonoscopy, 71% of non-microscopic colitis patients had bile acid diarrhoea. Baseline Shannon Index was lower in diarrhoea groups than in healthy controls (p = 0.0025); there were no differences between microscopic colitis, bile-acid diarrhoea and functional diarrhoea. The microbial dysbiosis index was significantly higher in microscopic colitis than in bile acid diarrhoea plus functional diarrhoea (p = 0.0095), but no bacterial species showed a significantly different relative abundance among the diarrheal groups.

Conclusions

Dysbiosis is a feature in active microscopic colitis, but loss of microbial diversity was similar in all diarrheal groups, suggesting that faecal microbial changes are not due to microscopic colitis itself but associated with stool form. A considerable number of microscopic colitis patients achieved clinical remission after colonoscopy, but we were unable to demonstrate related PEG-induced changes in faecal microbiome.
A study protocol of a randomized phase II trial of perioperative chemoimmunotherapy verses perioperative chemoimmunotherapy plus preoperative chemoradiation for locally advanced gastric (G) or gastroesophageal junction (GEJ) adenocarcinoma: the NeoRacing study
Authors: Zhou Menglong , Yang Wang , Xuan Yan , Zou Wei , Wang Yaqi , Zhang Zhiyuan , Zhang Jing , Mo Miao , Zhou Changming , Liu Yuan , Zhang Wenming , Zhang Zhaozhen , He Yiping , Weng Weiwei , Tan Cong , Wang Lei , Huang Dan , Sheng Weiqi , Li Huanhuan , Zhu Hui , Wang Yan , Shen Lijun , Zhang Hui , Wan Juefeng , Li Guichao , Huang Hua , Wang Yanong , Zhang Zhen , Liu Xiaowen , Xia Fan
Published: June 2022

Background

Perioperative chemotherapy (ChT) and preoperative chemoradiation (CRT) are both the standard treatments for locally advanced gastric cancer (LAGC). CRT can achieve a higher pathological complete regression (pCR) rate, but whether this higher pCR rate can be transformed into a long-term survival benefit remains inconclusive. Therefore, relevant studies are in progress. On the other hand, immunotherapy has been established for the first-line treatment of advanced gastric cancer (AGC) and has been widely explored in the perioperative setting. The combination of chemotherapy/radiotherapy and immunotherapy may have a synergistic effect, which will lead to a better antitumor effect. The preliminary reports of ongoing studies show promising results, including a further improved pCR rate. However, the preferred treatment combination for LAGC is still not established. To solve this problem, we are carrying out this randomized phase II trial, which aims to evaluate the efficacy and safety of perioperative chemotherapy plus the use of PD-1 antibody with or without preoperative chemoradiation for LAGC.

Methods

Eligible patients with LAGC or gastroesophageal junction (GEJ) adenocarcinoma were randomized to receive perioperative ChT, PD-1 antibody, surgery with (Arm A) or without preoperative CRT (Arm B), and PD-1 antibody maintenance until one year after surgery. The primary endpoint of this study is that the pCR rate of Arm A will be significantly higher than that of Arm B. The secondary endpoints include the pathological partial regression (pPR) rate, R0 resection rate, objective response rate (ORR), event-free survival (EFS), overall survival (OS), safety and surgical complications. Moreover, several explorative endpoints will be evaluated to find and validate the predictive biomarkers of immunotherapy.

Discussion

The results of the NeoRacing study will provide important information concerning the application of PD-1 antibody in LAGC patients during the perioperative setting. Meanwhile, the two treatment protocols will be compared in terms of efficacy and safety.

Trial registration

ClinicalTrials.gov, NCT05161572. Registered 17 December 2021 - Retrospectively registered.
Two-year follow-up of 90 children with autism spectrum disorder receiving intensive developmental play therapy (3i method)
Authors: Brefort Eloïse , Saint-Georges-Chaumet Yann , Cohen David , Saint-Georges Catherine
Published: June 2022

Background

The Intensive, Interactive, and Individual (3i) intervention approach aims to decrease the severity of autism spectrum disorder (ASD) using intensive developmental play therapy (3i). We performed a retrospective study of 90 children who were enrolled for 2 years in the 3i approach to assess changes and predictors of changes in ASD severity at follow-up (FU).

Methods

The ASD severity of all patients (N = 119) who began 3i intervention between 2013 and 2018 was systematically measured using the childhood autism rating scale (CARS) and autism diagnosis interview-revised (ADI-R). Among them, 90 patients (mean age 5.6 ± 3.7 years) had a second assessment at the 2 year FU. CARS and ADI-R scores after 2 years of 3i intervention were compared to baseline scores using paired student’s t-tests. We used multiple linear regression models to assess the weight of baseline variables (e.g., age, oral language, sex, treatment intensity) on changes at the 2 year FU.

Results

Mean CARS and ADI-R subscores (interaction, communication, repetitive behaviour) decreased significantly by 20, 41, 27.5 and 25%, respectively (effect sizes: d > 0.8). Moreover, 55 and 46.7% of participants switched to a lower category of ASD severity based on the CARS scale and ADI-R interview, respectively. Multiple linear models showed that (i) a higher treatment intensity (more than 30 h per week) was significantly associated with a greater decrease (improvement) in the ADI-R interaction score; (ii) patients categorized as verbal subjects at baseline were associated with a better outcome, as ascertained by the CARS, ADI-R interaction and ADI-R communication scores; and (iii) older patients were significantly associated with a greater decrease in the ADI-R interaction score. However, we found no impact of sex, severity of ASD or comorbidities at baseline.

Conclusion

This study performed on 90 children suggests that 3i therapy may allow for a significant reduction in ASD severity with improvements in interaction, communication, and repetitive behaviours. A study using a control group is required to assess the efficacy of 3i play therapy compared to other interventions.
Clinical features and treatment outcome of wrist tuberculosis in adult- a retrospective study of 84 consecutive cases with minimum of 2 years follow up
Authors: Yushan Maimaiaili , Yalikun Ainizier , Hamiti Yimurang , Lu Cheng , Yusufu Aihemaitijiang
Published: June 2022

Background

Wrist tuberculosis (TB) is a rare disease that may result in residual deformity, pain, or stiffness even after proper antitubercular chemotherapy (ATT) and surgical intervention. The aim of our study is to present clinical features and functional outcomes of wrist TB in a consecutive series of 84 adult patients with a minimum of 2 years of follow-up.

Methods

Clinical features and treatment outcomes of 84 consecutive adult patients with wrist TB from January 2003 to June 2018 including 45 men and 39 women, with a mean age of 46.8 years (18–84) were retrospectively analyzed. Data were collected on participants’ demographic details. The primary outcome measures were QuickDASH score, grip strength, Visual Analogue Scale (VAS), and PRWHE. Secondary outcomes include health-related quality of life was evaluated using the EuroQol five-dimension five-level (EQ-5D-5L), assessment and postoperative complications of patients who underwent operation were also recorded.

Results

All 84 patients with an average follow-up of 50.8 (24–105) months. The mean duration of symptoms before treatment was 10.5 months (2–21). There were 27 patients with bony and 57 with primarily soft-tissue involvement based on preoperative evaluation of plain radiographs and MRI. There were 33 patients treated with ATT and 51 patients were treated with surgery followed by ATT. Among them, 13 patients (15.5%) underwent incision and decompression, 14 patients (16.7%) underwent wrist synovectomy, 13 patients (15.5%) underwent wrist joint fusion by plate fixation, and 11 patients (13.1%) underwent wrist joint fusion by external fixation. At the last clinical visit, the QuickDASH, and PRWHE scores of all patients decreased significantly, the VAS improved from 5.9 to 1.4, EQ-5D-5L utility index improved from 0.36 to 0.88, EQ-VAS improved from 40.2 to 89.1. All patients indicated good wrist recovery at the last follow-up, and the treatment achieved satisfactory clinical outcomes.

Conclusion

The onset of wrist TB is insidious; early diagnosis, good patient compliance, and surgery combined with ATT are crucial steps for treatment of wrist TB, and also essential for the patient's postoperative recovery. Wrist arthrodesis has achieved satisfactory results in the treatment of severe wrist TB.
Increase in Bifidobacterium is a characteristic of the difference in the salivary microbiota of pregnant and non-pregnant women
Authors: Kato Satsuki , Nagasawa Toshiyuki , Uehara Osamu , Shimizu Shintaro , Sugiyama Nodoka , Hasegawa-Nakamura Kozue , Noguchi Kazuyuki , Hatae Masayuki , Kakinoki Hiroshige , Furuichi Yasushi
Published: June 2022

Background

The establishment of symbiotic microbiota in pregnant women is important for both the mother and her offspring. Little is known about the salivary symbiotic bacteria in pregnancy, and analysis of composition of microbiome (ANCOM) is useful to detect small differences in the number of bacteria. The aim of this study was to investigate the differences in the salivary bacteria between healthy pregnant and non-pregnant women using ANCOM.

Methods

Unstimulated saliva samples were collected from 35 healthy pregnant women at 35 weeks gestation and 30 healthy non-pregnant women during menstruation. All participants underwent a periodontal examination. Estradiol and progesterone levels were examined by enzyme-linked immunosorbent assay. DNA extracted from the saliva was assessed by 16S ribosomal RNA amplicon sequencing and real-time PCR.

Results

Salivary estradiol and progesterone levels were significantly increased in pregnant women. The alpha and beta diversities were higher in pregnant women than in non-pregnant women. The largest effect size difference noted when the microbiota of the pregnant and non-pregnant women were analyzed was that for Bifidobacteriales. Levels of Bifidobacterium dentium, but not of Bifidobacterium adolescentis, were significantly increased in pregnant women, and the levels were significantly correlated with progesterone concentration.

Conclusion

The results suggest that Bifidobacterium and progesterone levels are elevated in the saliva of healthy pregnant women compared with non-pregnant women.
A rare case of multiple brain abscesses caused by apical periodontitis of deciduous teeth in congenital heart disease: a case report
Authors: Takahashi Shizuka , Segoe Hisato , Kikuiri Takashi , Maruo Yuji , Sato Tomonobu , Watanabe Yutaka , Jimei Zhao , Yoshimura Yoshitaka , Ishiyama Misa , Takeda Atsuhito , Yawaka Yasutaka , Shirakawa Tetsuo
Published: June 2022

Background

A brain abscess is a focal infection in which abscesses form in the brain. A brain abscess is a rare but fatal disease when rupture occurs into the ventricles. We report a case of multiple brain abscesses caused by a hematogenous infection from the apical periodontitis of deciduous teeth.

Case presentation

The patient was a 7-years and 8-months-old male with congenital heart disease. The patient sought medical attention due to fever and headache, for which he was started on three antibiotics with a diagnosis of multiple brain abscesses. Given that apical periodontitis of deciduous teeth was strongly suspected as the source of the brain abscess, the deciduous teeth were extracted. Immediately after deciduous teeth extraction, the patient’s headache and neurological symptoms disappeared.

Conclusions

After teeth extraction, a clear shrinkage of the brain abscess was observed, and the patient was discharged from the hospital.
The impact and feasibility of a brief, virtual, educational intervention for home healthcare professionals on Parkinson’s Disease and Related Disorders: pilot study of I SEE PD Home
Authors: Hess Serena P. , Levin Melissa , Akram Faizan , Woo Katheryn , Andersen Lauren , Trenkle Kristie , Brown Patricia , Ouyang Bichun , Fleisher Jori E.
Published: June 2022

Background

Individuals with advanced Parkinson’s Disease (PD) and Parkinson-related disorders (PRD) are frequently referred for home allied therapies and nursing care, yet home healthcare professionals have limited training in PD/PRD. While recognizing the need for such care, patients and families report home healthcare professionals are unfamiliar with these conditions, which may be driven by neurophobia and may contribute to suboptimal care and early termination of services. We sought to determine the feasibility and effects of a virtual, multimodal educational intervention on PD knowledge, confidence, and empathy among home health professionals.

Methods

Home health nurses, occupational therapists, physical therapists and physical therapy assistants, and speech-language pathologists participated in a daylong, virtual symposium on advanced PD/PRD, combining focused lectures, discipline-specific breakout sessions, immersive virtual reality vignettes, and interactive panels with both patients and families, and movement disorders and home healthcare experts. Participants completed online pre- and post-symposium surveys including: demographics; PD/PRD knowledge (0–10 points possible); empathy (Interpersonal Reactivity Index); and 10-point scales of confidence with and attitudes towards individuals with PD/PRD, respectively. Pre-post intervention changes and effect sizes were evaluated with paired t-tests and Cohen’s d. We performed qualitative analyses of post-symposium free-text feedback using a grounded theory approach to identify participants’ intentions to change their practice.

Results

Participants had a mean improvement of 3.1 points on the PD/PRD knowledge test (p < 0.001, d = 1.97), and improvement in confidence managing individuals with PD/PRD (p = 0.0003, d = .36), and no change in empathy. The interactive, virtual format was rated as effective by 95%. Common themes regarding symposium-motivated practice change included: interdisciplinary collaboration; greater involvement and weighting of the patient and caregiver voice in care plans; attention to visit scheduling in relation to patient function; recognition and practical management of the causes of sudden change in PD/PRD, including infections and orthostatic hypotension.

Conclusions

A virtual, multimodal, brief educational pilot intervention improved PD/PRD-specific knowledge and confidence among home healthcare nurses and allied health professionals. Future studies are necessary to test the short- and long-term effects of this intervention more broadly and to investigate the impact of this education on patient and caregiver outcomes.
The nurse teacher’s pedagogical cooperation with students, the clinical learning environment and supervision in clinical practicum: a European cross-sectional study of graduating nursing students
Authors: Strandell-Laine Camilla , Salminen Leena , Blöndal Katrín , Fuster Pilar , Hourican Susan , Koskinen Sanna , Leino-Kilpi Helena , Löyttyniemi Eliisa , Stubner Juliane , Truš Marija , Suikkala Arja
Published: June 2022

Background

A supportive clinical practicum experience may enhance the successful transition and socialization to working life of graduating nursing students. Nurse teachers have the main responsibility of supporting and guiding nursing students with their pedagogical expertise during the students’ clinical practicum. Thus, the clinical role of nurse teachers is seen as an essential part of a high-quality clinical practicum. Nursing students appreciate the nurse teacher’s cooperation with students, but it is often reported to be unattainable. The aim of this study was to explore and compare graduating nursing students’ experiences of the nurse teacher’s pedagogical cooperation with students, the clinical learning environment and supervision in their final clinical practicum, and to analyze factors associated with these experiences in six European countries.

Methods

A cross-sectional comparative international survey design was used. The modified Clinical Learning Environment, Supervision and Nurse Teacher (CLES+T) Scale, with a new subscale measuring the nurse teacher’s pedagogical cooperation with students, was used. A convenience sample of graduating nursing students in Finland, Germany, Iceland, Ireland, Lithuania and Spain completed the online survey in 2018–2019. The data were analyzed using a Chi-Square test, Pearson’s correlation coefficients, and linear models.

Results

A total of 1796 (response rate 49%) nursing students completed the survey. Overall, students had positive experiences of the nurse teacher’s pedagogical cooperation, the clinical learning environment and supervision in their final clinical practicum. Students in Spain had the most positive experiences. Educational background factors appeared to be associated with the students’ experiences of the nurse teacher’s pedagogical cooperation with students, the clinical learning environment and supervision. The relationships between the subscale Nurse teacher’s pedagogical cooperation with students and the Clinical Learning Environment and Supervision Scale were perceived as weak to strong depending on the country.

Conclusions

This study reveals that nurse teachers play an essential role in supporting and guiding nursing students’ final clinical practicum. In this light, researchers, educators, and leaders should collaborate seamlessly between educational institutions and healthcare organizations to establish the nurse teachers’ pedagogical cooperation role within the clinical learning environment.
Medical students describe their wellness and how to preserve it
Authors: Chatterjee Krishanu , Edmonds Victoria S. , Girardo Marlene E. , Vickers Kristin S. , Hathaway Julie C. , Stonnington Cynthia M.
Published: June 2022

Background

Despite widespread efforts to create wellness programming in medical schools, there is a paucity of literature examining students’ perception of wellness and perceptions of these programs. With the inaugural class at the Arizona campus of Mayo Clinic Alix School of Medicine (MCASOM-AZ), an opportunity arose to establish an empirically evaluated wellness curriculum that most inclusively and effectively enables medical students to flourish for years to come. The initial wellness offerings included mental health, academic success, and disability services, curriculum-embedded seminars, wellness committee driven programming, and student-proposed wellness activities. We aimed to improve the relevance and impact of medical school wellness curricula by soliciting in-depth and longitudinal perspectives of medical students themselves. As MCASOM-AZ opened in 2017, the student body at the time of study consisted of first- and second-year medical students.

Methods

Employing a mixed methods analysis of qualitative and longitudinal quantitative data, first- and second-year students at a MCASOM-AZ were invited to respond to an anonymous, online year-long survey (baseline, six months and 12 months) during the 2018–2019 academic year and participate in a structured, in-depth and in-person, peer-to-peer interview about their conceptions of wellness and the MCASOM-AZ wellness curriculum and resources. Qualitative data was coded for themes using thematic analysis strategies by independent raters.

Results

Nearly half of eligible students completed the baseline survey,1/3 completed all 3 time-points, and 1/5 participated in an in-depth interview. Participant age, gender, and year of school were representative of the larger student body. Although individual conceptions varied, Wellness was consistently highly valued. Family, Academic Performance, and Friends emerged as most important to well-being across time-points. Academic work arose as the largest barrier to wellness. Analysis of qualitative data revealed five themes. Despite individual differences in approaches to wellness, wellbeing was interrelated to the learning environment; mandatory wellness efforts that didn’t address the medical culture met with skepticism.

Conclusions

Interview responses provided understanding and context by which to interpret questionnaire responses. Academics was critical to students’ identity and wellness, while also the largest barrier. Suggested curricular improvements include restructuring academic work, seamlessly integrating wellness within coursework, and offering optional individualized approaches.
The down-regulation of XBP1, an unfolded protein response effector, promotes acute kidney injury to chronic kidney disease transition
Authors: Chen Jia-Huang , Wu Chia-Hsien , Jheng Jia-Rong , Chao Chia-Ter , Huang Jenq-Wen , Hung Kuan-Yu , Liu Shing-Hwa , Chiang Chih-Kang
Published: June 2022

Background

The activation of the unfolded protein response (UPR) is closely linked to the pathogenesis of renal injuries. However, the role of XBP1, a crucial regulator of adaptive UPR, remains unclear during the transition from acute kidney injury (AKI) to chronic kidney disease (CKD).

Methods

We characterized XBP1 expressions in different mouse models of kidney injuries, including unilateral ischemia–reperfusion injury (UIRI), unilateral ureteral obstruction, and adenine-induced CKD, followed by generating proximal tubular XBP1 conditional knockout (XBP1cKO) mice for examining the influences of XBP1. Human proximal tubular epithelial cells (HK-2) were silenced of XBP1 to conduct proteomic analysis and investigate the underlying mechanism.

Results

We showed a tripartite activation of UPR in injured kidneys. XBP1 expressions were attenuated after AKI and inversely correlated with the severity of post-AKI renal fibrosis. XBP1cKO mice exhibited more severe renal fibrosis in the UIRI model than wide-type littermates. Silencing XBP1 induced HK-2 cell cycle arrest in G2M phase, inhibited cell proliferation, and promoted TGF-β1 secretion. Proteomic analysis identified TNF receptor associated protein 1 (Trap1) as the potential downstream target transcriptionally regulated by XBP1s. Trap1 overexpression can alleviate silencing XBP1 induced profibrotic factor expressions and cell cycle arrest.

Conclusion

The loss of XBP1 in kidney injury was profibrotic, and the process was mediated by autocrine and paracrine regulations in combination. The present study identified the XBP1-Trap1 axis as an instrumental mechanism responsible for post-AKI fibrosis, which is a novel regulatory pathway.
The risk of incident atrial fibrillation in patients with type 2 diabetes treated with sodium glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists, and dipeptidyl peptidase-4 inhibitors: a nationwide cohort study
Authors: Chan Yi-Hsin , Chao Tze-Fan , Chen Shao-Wei , Lee Hsin-Fu , Li Pei-Ru , Chen Wei-Min , Yeh Yung-Hsin , Kuo Chi-Tai , See Lai-Chu , Lip Gregory Y. H.
Published: June 2022

Background

Although a few meta-analyses were conducted to compare the risk of incident atrial fibrillation (AF) between sodium-glucose cotransporter-2 inhibitor (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and other anti-hyperglycemic agents using indirect or direct comparison, the above analyses showed conflicting results with each other. We aimed to evaluate the risk of new-onset AF associated with the use of SGLT2i, GLP-1RA, and dipeptidyl peptidase-4 inhibitor (DPP4i) among a large longitudinal cohort of diabetic patients.

Methods

In this nationwide retrospective cohort study based on the Taiwan National Health Insurance Research Database, a total of 344,893, 44,370, and 393,100 consecutive patients with type 2 diabetes without preexisting AF receiving GLP-1RA, SGLT2i, and DPP4i, respectively, were enrolled from May 1, 2016, to December 31, 2019. We used 1:1 propensity score matching (PSM) to balance covariates across paired study groups. Patients were followed from the drug index date until the occurrence of AF, death, discontinuation of the index drug, or the end of the study period (December 31, 2020), whichever occurred first.

Results

After PSM, there were 245,442, 43,682, and 39,190 paired cohorts of SGLT2i-DPP4i, SGLT2i-GLP-1RA, and GLP-1RA-DPP4i, respectively. SGLT2i treatment was associated with lower risk of new-onset AF in participants with type 2 diabetes compared with either DPP4i [hazard ratio (HR):0.90; 95% confidential interval (CI) 0.84–0.96; P = 0.0028] or GLP-1RA [HR 0.74; 95% CI 0.63–0.88; P = 0.0007] treatment after PSM. There was no difference in the risk of incident AF between GLP-1RA and DPP4i users [HR 1.01; 95% CI 0.86–1.19; P = 0.8980]. The above findings persisted among several important subgroups. Dapagliflozin was specifically associated with a lower risk of new-onset AF compared with DPP4i (P interaction = 0.02).

Conclusions

Compared with DPP4i, SGLT2i but not GLP-1RA was associated with a lower risk of incident AF in patients with type 2 diabetes.
Improve individual treatment by comparing treatment benefits: cancer artificial intelligence survival analysis system for cervical carcinoma
Authors: Liang Jieyi , He Tingshan , Li Hong , Guo Xueqing , Zhang Zhiqiao
Published: June 2022

Purpose

The current study aimed to construct a novel cancer artificial intelligence survival analysis system for predicting the individual mortality risk curves for cervical carcinoma patients receiving different treatments.

Methods

Study dataset (n = 14,946) was downloaded from Surveillance Epidemiology and End Results database. Accelerated failure time algorithm, multi-task logistic regression algorithm, and Cox proportional hazard regression algorithm were used to develop prognostic models for cancer specific survival of cervical carcinoma patients.

Results

Multivariate Cox regression identified stage, PM, chemotherapy, Age, PT, and radiation_surgery as independent influence factors for cervical carcinoma patients. The concordance indexes of Cox model were 0.860, 0.849, and 0.848 for 12-month, 36-month, and 60-month in model dataset, whereas it were 0.881, 0.845, and 0.841 in validation dataset. The concordance indexes of accelerated failure time model were 0.861, 0.852, and 0.851 for 12-month, 36-month, and 60-month in model dataset, whereas it were 0.882, 0.847, and 0.846 in validation dataset. The concordance indexes of multi-task logistic regression model were 0.860, 0.863, and 0.861 for 12-month, 36-month, and 60-month in model dataset, whereas it were 0.880, 0.860, and 0.861 in validation dataset. Brier score indicated that these three prognostic models have good diagnostic accuracy for cervical carcinoma patients. The current research lacked independent external validation study.

Conclusion

The current study developed a novel cancer artificial intelligence survival analysis system to provide individual mortality risk predictive curves for cervical carcinoma patients based on three different artificial intelligence algorithms. Cancer artificial intelligence survival analysis system could provide mortality percentage at specific time points and explore the actual treatment benefits under different treatments in four stages, which could help patient determine the best individualized treatment. Cancer artificial intelligence survival analysis system was available at:https://zhangzhiqiao15.shinyapps.io/Tumor_Artificial_Intelligence_Survival_Analysis_System/.
Dual block HER2 assessment increased HER2 immunohistochemistry positive rate in resected specimens of gastric cancer: a prospective multicenter clinical trial from China
Authors: Xu Chen , Sun Miaomiao , Jin Mei , Li Zengshan , Qin Rong , Ren Guoping , Sun Wenyong , Chen Lirong , Luan Lijuan , Liu Yalan , Jiang Dongxian , Chen Lingli , Luo Rongkui , Hou Yingyong
Published: June 2022

Background

Former single center studies indicated that HER2 assessment with two primary tumor blocks (dual block HER2 assessment) could be an efficient and practical approach to overcome the adverse impact of heterogeneity and acquire a HER2 positive rate in gastric cancer (GC). This multicenter prospective clinical trial (NCT 02843412) was launched to verify its value and generality.

Methods

A total of 3806 participants with primary GCs have been enrolled from 8 hospitals in China. Two primary tumor blocks were selected and recorded as block 1 and block 2 after histological evaluation. An HER2 (4B5) rabbit monoclonal antibody was used for the immunohistochemistry (IHC) analysis.

Results

In total patients, HER2 IHC positive (3+) rate with dual block assessment (9.4%) was higher than that with single block assessment (block 1: 7.8%, block 2: 7.8%) (P < 0.001). Compared with single-block assessment, dual-block assessment increased the positive rate by approximate 20%. Similarly, HER2 equivocal (2+) rate was increased in dual block assessment (25.8%), which was higher than that in single block assessment (block 1: 20.3%, block 2: 20.9%) (P < 0.001). Conversely, dual block assessment demonstrated a lower HER2 negative (0/1+) rate (64.8%) than single block assessment (block1: 71.9%, block 2: 71.3%) (P < 0.001). These findings were also confirmed in individual hospitals.

Conclusions

Dual block HER2 assessment effectively increased HER2 IHC positive rate in resected specimens of GC. We recommended dual block HER2 assessment be promoted in routine clinical practice in GC.

Trial registration

ClinicalTrials.gov, NCT 02843412. Registered 1 July 2016 - Retrospectively registered.
Ex vivo fluorescence confocal microscopy: chances and changes in the analysis of breast tissue
Authors: Nackenhorst Maja Carina , Kasiri Mohammad , Gollackner Bernd , Regele Heinz
Published: June 2022

Background

Rapid histologic diagnosis of frozen sections is essential for a variety of surgical procedures. Frozen sections however, require specialized lab equipment, are prone to freezing artifacts and are not applicable to all types of tissue. Adipose tissue is especially difficult to process in frozen sections. Although these limitations are well known, no alternative method for microscopic tissue analysis that might replace frozen sections could be established. Our objective was to evaluate whether tissue imaging based on ex vivo fluorescent confocal microscopy (FCM) is applicable for rapid microscopic assessment of breast tumors specimens with abundant adipose tissue.

Methods

We evaluated 17 tissue samples from mastectomy specimens, rich in adipose tissue, submitted to the department of pathology at the Medical University of Vienna. We conducted our study on the FCM VivaScope® 2500M-G4 (Mavig GmbH, Munich, Germany; Caliber I.D.; Rochester NY, USA).

Results

When comparing FCM to frozen sections, we found a very similar overall processing time for FCM images and frozen sections respectively. Image quality was mostly superior to frozen sections (especially for adipose tissue and nuclear detail) but inferior to H&E stained FFPE sections. Limitations of the technology were uneven coloring, invisibility of ink applied for marking tissue margins and distortion artifacts if too much pressure is applied to the tissue.

Conclusion

FCM has the potential to expand the application and usefulness of rapid tissue analysis as speed is comparable and quality exceeds that of frozen sections especially in tissues rich in adipose cells such as breast specimen.
Economic evaluation of a multi-strategy intervention that improves school-based physical activity policy implementation
Authors: Lane Cassandra , Nathan Nicole , Reeves Penny , Sutherland Rachel , Wolfenden Luke , Shoesmith Adam , Hall Alix
Published: June 2022

Background

Internationally, government policies mandating schools to provide students with opportunities to participate in physical activity are poorly implemented. The multi-componentPhysically Active Children in Education(PACE) intervention effectively assists schools to implement one such policy. We evaluated the value of investment by health service providers tasked with intervention delivery, and explored where adaptations might be targeted to reduce program costs for scale-up.

Methods

A prospective trial-based economic evaluation of an implementation intervention in 61 primary schools in New South Wales (NSW), Australia. Schools were randomised to the PACE intervention or a wait-list control. PACE strategies included centralised technical assistance, ongoing consultation, principal's mandated change, identifying and preparing in-school champions, educational outreach visits, and provision of educational materials and equipment. Effectiveness was measured as the mean weekly minutes of physical activity implemented by classroom teachers, recorded in a daily log book at baseline and 12-month follow-up. Delivery costs (reported in $AUD, 2018) were evaluated from a public finance perspective. Cost data were used to calculate: total intervention cost, cost per strategy and incremental cost (overall across all schools and as an average per school). Incremental cost-effectiveness ratios (ICERs) were calculated as the incremental cost of delivering PACE divided by the estimated intervention effect.

Results

PACE cost the health service provider a total of $35,692 (95% uncertainty interval [UI] $32,411, $38,331) to deliver; an average cost per school of $1151 (95%UI $1046, $1236). Training in-school champions was the largest contributor: $19,437 total; $627 ($0 to $648) average per school. Educational outreach was the second largest contributor: $4992 total; $161 ($0 to $528) average per school. The ICER was $29 (95%UI $17, $64) for every additional minute of weekly physical activity implemented per school.

Conclusion

PACE is a potentially cost-effective intervention for increasing schools implementation of a policy mandate. The investment required by the health service provider makes use of existing funding and infrastructure; the additional cost to assist schools to implement the policy is likely not that much. PACE strategies may be adapted to substantially improve delivery costs.

Trial registration

Australia New Zealand Clinical Trials Registry ACTRN12617001265369; Prospectively registered 1st September 2017https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373520
COVID-19 in Fabry disease: a reference center prospective study
Authors: Bothou Christina , Saleh Lanja , von Eckardstein Arnold , Beuschlein Felix , Nowak Albina
Published: June 2022

Background

During the coronavirus disease-19 (COVID-19) pandemic, vulnerable populations must be identified to prevent increased mortality. Fabry disease (FD) is a rare X-linked lysosomal storage disorder leading to chronic kidney disease (CKD), cardiomyopathy, pneumonopathy and premature strokes. Little is known whether SARS-CoV-2 infection bears a particular risk for FD patients.

Methods

During pandemic (02.2020–03.2021) we have regularly followed 104 unvaccinated FD patients. In 61/104, titre of serum antibodies against SARS-CoV-2 were measured and SARS-CoV-2 PCR test was performed in symptomatic patients or in case of positivity of other family members. The symptoms and duration of COVID-19 were reported by the patients or the treating physician.

Results

No deaths or intensive care unit hospitalizations occurred. 13/104 (12.5%) were diagnosed with SARS-CoV-2 infection (16.7% (4/24) men 12.2% (6/49) women of classic phenotype, 25% (3/12) of the men and 0% (0/8) of the women of later- onset phenotype). Of those, 2/13 (15.4%) patients—both kidney transplant recipients—developed severe COVID-19, were hospitalized, and required a high-flow oxygen mask. The rest either developed mild COVID-19 manifestations (8/13, 61.5%) or were asymptomatic (3/13, 23.1%). 2/13 (15.4%) of the patients experienced Fabry pain crisis and 3/13 (23.1%) long COVID-19 like symptoms.

Conclusions

Similar to the general population, in FD patients the risk for severe COVID-19 seems to be driven by the immune system rather than by FD itself. Immunosuppression in kidney transplant recipients represented the highest risk in this population.