bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient interpretations vary for questions in the Patient-Reported Outcomes Measurement Information System Upper Extremity
Authors: Azad Chao Long , Beres Laura K. , Wu Albert W. , Giladi Aviram M.
Published: April 2023

The Patient-Reported Outcomes Measurement Information System Upper Extremity (PROMIS-UE) is frequently used in research/clinical care, but how it is understood by patients is unknown. We conducted a qualitative study including 12 cognitive interviews with patients with hand/upper extremity conditions and those purposively sampled for mixed literacy. Using framework analysis, we identified six themes total: difficulty answering questions due to insufficient information; uncertainty about whether to respond with the ability to perform the task with the injured extremity alone, either the injured or healthy extremity, or both; lack of experience doing certain tasks; uncertainty about whether to answer questions based on ability to perform the task with or without adaptive techniques; answering questions based on limitations not related to upper extremity function; and uncertainty regarding whether to answer questions on the basis of ability or pain. This study demonstrates the challenges in completing questionnaires and that variability may limit the reliability, validity and responsiveness of the PROMIS-UE.
Bony hip reconstruction for displaced hips in patients with cerebral palsy: Is postoperative immobilization indicated?
Authors: Amen John , Perkins Oliver , Kafchitsas Konstantinos , Reed Daniel , Norman-Taylor Fabian , Kokkinakis Michail
Published: April 2023

Purpose:

Decisions for postoperative immobilization after bony hip reconstructive surgery in cerebral palsy are controversial in current practice. The aim of this study was to check if choosing not to use any kind of postoperative immobilization is a safe practice.

Methods:

A retrospective cohort study was conducted in a pediatric orthopedic tertiary referral center. The study included 148 patients (228 hips) with cerebral palsy, who had bony hip surgery. Medical records were reviewed for incidence of complications, methods of pain control, and length of hospital stay. Three radiographic measures (neck-shaft angle, Reimers migration index, and acetabular index) were performed on preoperative and postoperative X-rays. X-rays were also checked for mechanical failure of implant, recurrent dislocation/subluxation, and fractures in the first 6 months postoperatively.

Results:

In total, 94 (64%) were male and 54 (36%) were female. Seventy-seven (52%) were Gross Motor Function Classification System V, mean age at surgery was 8.6 years (2.5–18.4 years). Length of hospital stay was 6.25 days (SD 4.64 days). Medical complications that may have prolonged hospital stay occurred in 41 patients (27.7%). Radiological measurements showed significant improvement postoperatively ( p = 0.001). Seven patients (4.7%) had another surgery in first 6 months (three for recurrent dislocation/subluxation, three for implant failure, and one for ipsilateral femur fracture).

Conclusion:

Avoiding postoperative immobilization following bony hip surgery in cerebral palsy is a safe practice and associated with reduced rate of medical and mechanical problems compared to the current literature. This approach should be utilized with optimal pain and tone management.
Digital dashboards with paradata can improve data quality where disease surveillance relies on real-time data collection
Authors: Gupta Sanjeev K , Singh Himmat , Joshi Mahesh C , Sharma Amit
Published: April 2023

Dealing with the threats of vector-borne diseases necessitates robust disease surveillance systems. The gathered information from surveillance studies is used to evaluate the effectiveness of control measures. It also guides the allocation of resources within the healthcare system. The disease surveillance data also identify high-risk populations or geographic areas to target interventions. Because of the importance of surveillance in decision-making and its timely requirement, real-time data collection is vital. A few advantages of real-time data collection apps are building powerful digital forms, exporting data for quick analysis in various formats, and being open-source. These apps automate data collection and transfer to an online server even without an internet connection. While collecting disease surveillance data digitally one crucial aspect lacking is data quality. This paper aims to present the importance of dashboards that includes paradata in improving data quality using real-time data collection tools in disease surveillance. Various types of paradata such as timestamps, geo-referencing, audio recording and so on help enhance the quality of data and can help monitor and evaluate surveillance staff. The outcomes of the paradata analysis may lead to the retraining of the surveillance team and even re-planning of surveillance. Undoubtedly, real-time data collection is the way of the future in any field-based study, and studies should be planned in conjunction with paradata to ensure that high-quality data are recorded.
Understanding layered dominance of political dynasties in India: A de-hyphenated reading of dynastic representation and dynasty-led parties
Authors: Ghosh Ambar Kumar
Published: April 2023

India has witnessed the dominance of a plethora of political dynasties, both at the national as well as the state level, since independence. The post-colonial Indian state adopted a liberal constitutional democracy premised upon modern representative institutions. However, the primordial principle of hereditary succession of power resiliently co-existed in the form of powerful political families that have continued to impact the nature of Indian democratic political discourse till today. The political parties are an instrumental driver of political life in all modern representative democracies including India. Hence, it is crucial to study how the Indian party system has consolidated the prominence of political dynasties especially from the 1970s onwards, in the realm of both party organisation and the representative institutions. In this context, the article attempts to problematise the nature of dynastic politics in India and offers a framework to analyse the causes of its dominance to understand how it impacts the right to equal political opportunity and electoral competitiveness. The article makes three arguments. First, to better understand the amorphous nature of dynastic politics, two elements – dynastic representation in elected institutions and dynasty-led parties – need to be studied distinctively, despite some commonalities. Second, dynastic representation is largely ubiquitous in most political parties (in both dynasty-led and non-dynasty-led parties) due to the party's preference for legacy candidates and their higher chances of electoral winnability. Third, the article offers two typologies of dynasty-led parties, explaining why the dynasties’ grip over their parties, particularly in recent times, appears to be mostly performance-immune and in what circumstances some dynasty-led parties not only perform better in electoral contests than others but also face tough competition for retaining their dynastic control over the party. Lastly, the article concludes with some reflections on how dynastic representation and dynasty-led parties impact the form and substance of the Indian party system and democratic politics.
Patient Satisfaction as a Determinant of Patient Loyalty to the Dentist in Dental Clinics
Authors: El Dalatony Mervat M. , Alshareef Rahaf I. , Alkahtani Abeer R. , Alhajri Shahad M. , Alhumaidany Turki M. , AlQarni Waleed A. , Almuaddi Afnan M. , Aldossary Mohammed S.
Published: April 2023

The aim of this study was to investigate the impact of patient satisfaction with a dentist on their loyalty to that dentist in Saudi Ministry of Health dental clinics. Retrospective data were recruited from the patient experience program (Press Ganey Survey) during the first half of 2022. Descriptive statistical analysis, Pearson correlation coefficient ( r), and multiple linear regression models were used to assess the impact on loyalty to that dentist. Among the 964 respondents who submitted their responses to the survey, the highest mean satisfaction score was for the item concerning the good listening of the dentist to the patient (3.86 of 5; 77.2%). There was a highly significant correlation between each item related to the dentist and the likelihood of the patient to recommend a certain dentist to others “that is, patient loyalty” ( P < .001). The highest predictor of patient loyalty to his dentist was the dentist's explanation of the treatment options to his patient ( t: 8.632, P < .001). Dentists have a crucial role to play in boosting patient satisfaction and thereby patient loyalty.
Kidney function while on immune checkpoint inhibitors: Trends in incidence of acute kidney injury, and its causes and outcomes
Authors: Garcia Pablo , Stedman Margaret R , Merlo Shayli , Kaghazchi Aydin , Reddy Sunil , Katsumoto Tamiko R , Anand Shuchi
Published: April 2023

Background and objectives:

Immune checkpoint inhibitor (ICI) use is increasing in the United States, real world data on acute kidney injury (AKI) in the expanding population are sparse. We evaluated trends in AKI incidence, and causes and management of AKI among 1914 persons receiving ICIs in a single center over a period of 5 years.

Methods:

We included all adults who received ICIs at the Stanford Healthcare System from July 1, 2015 to June 30, 2020. We defined AKI as an increase in serum creatinine to 1.5 times the baseline or an increase of ⩾0.3 mg/dL, and determined mean cumulative incidence of first and repeated episodes of AKI over three time periods.

Results:

Among the 1914 patients treated with ICIs, mean age was 64.9 (SD 14.3) years, 43% were women, 25% had baseline chronic kidney disease (CKD), 34% had lung and 23% had skin cancer as the indication. The overall cumulative incidence of any AKI and immune-related AKI at 1 year after initiating immunotherapy was 32% and 1.3% respectively. Among 586 cases of AKI, the most common cause was volume depletion (64%). Although 4% of AKI was immune-related, ICI therapy was discontinued in 14% of patients with AKI. Nephrology was consulted in 6%. The risk for AKI was higher among patients with a comorbidity index ⩾3 (vs CMI 0, HR 1.65 [95% CI 1.26–2.17]), digestive system cancer (vs skin cancer, 1.65 [1.13–2.43]), and lower baseline estimated glomerular filtration rate (30–59 and <30 vs >60) (HR 1.69 [1.32–2.16] and 1.85 [1.16–2.97] respectively).

Conclusions:

AKI occurs in up to 1 in 3 patients, and 1 in 10 will have repeated episodes during the first year of ICI therapy. Incidence of AKI has remained similar over 5-year time span. The cause of AKI while on ICI is rarely an immune-related adverse event.
Evaluating curriculum for student funds of knowledge: A review of project WET 2.0
Authors: Hileman Jennifer , Olsen Emily , Plummer Julia D
Published: April 2023

Environmental education programs have been shown to produce numerous positive outcomes for participants. However, literature also shows that imbalances may exist regarding the distribution of those outcomes and discrepancies related to affordance of benefits to diverse populations; in some instances, those discrepancies do not simply lack inclusion, but perpetuate the exclusion of certain individuals. While there are likely many factors and potential solutions related to this discrepancy, a closer look at student funds of knowledge within learning context may provide insight regarding program modifications. Incorporating student funds of knowledge within a learning experience has been shown to benefit learners and support more meaningful experiences. The present paper presents an evaluation tool designed to measure the extent to which a curriculum incorporates student funds of knowledge. Further, we demonstrate the use of this evaluation tool through the examination of an existing curriculum: Project WET 2.0. The curriculum provided limited opportunities to incorporate student funds of knowledge. Students participating in Project WET 2.0 may not experience the benefits associated with incorporating student funds of knowledge including stronger connections between outside worlds and classroom content.
Nudging General Practitioners to explore suicidal thoughts among depressed patients
Authors: Elzinga Elke , de Beurs Derek P. , Beekman Aartjan T.F. , Maarsingh Otto R. , Gilissen Renske
Published: April 2023

Background

While frank discussion of suicidal thoughts in patients with depression is important for the prevention of suicide, suicide exploration of General Practitioners (GPs) is suboptimal. This study aimed to assess whether an intervention that prompts pop-up screens nudges GPs to more frequently explore suicidal thoughts over the course of two years.

Methods

From January 2017 to December 2018, the intervention was incorporated in the information system of the Dutch general practice sentinel network. New registration of an episode of depression triggered a pop-up screen referring to a questionnaire about GPs’ behaviour with regard to exploring suicidal thoughts. In two years, 625 questionnaires were completed by GPs and analysed using multilevel logistic regression analyses.

Results

Compared to the first year, GPs were 50% more likely to explore suicidal thoughts among patients in the second year (OR 1.48; 95%CI 1.01–2.16). When adjusting for patients’ gender and age we found that the effect of the pop-up screens disappeared (OR 1.33; 95% CI 0.90–1.97). Suicide exploration occurred less frequently in women than in men (OR 0.64; 95% CI 0.43–0.98) and in older compared to younger patients (OR 0.97; 95% CI 0.96–0.98 per year older). In addition, 26% of variation in suicide exploration was because of differences in general practice. There was no evidence that general practices developed differently over time.

Conclusions

Although low cost and easy to administer, the pop-up system was not effective in nudging GPs to explore suicidality more frequently. We encourage studies to test whether implementing these nudges as part of a multifaceted approach will lead to a stronger effect. Moreover, we recommend researchers to include more variables, such as work experience or previous mental health training, to better understand the effects of the intervention on GPs’ behaviour.
Cultural beliefs and practices on perinatal death: a qualitative study among the Lango community in Northern Uganda
Authors: Arach Anna Agnes Ojok , Nakasujja Noeline , Rujumba Joseph , Mukunya David , Odongkara Beatrice , Musaba Milton W. , Napyo Agnes , Tumwine James K. , Nankabirwa Victoria , Ndeezi Grace , Kiguli Juliet
Published: April 2023

Background

Perinatal death has profound psychosocial effects on women and their families. Sociocultural contexts influence the burden, rituals and bereaved’s support. Little is known about cultural beliefs and practices related to perinatal death. This study explored the cultural perspectives of the Lango community on perinatal death.

Methods

This study utilised a focused ethnographic design anchored on a symbolic interactionist framework to understand the meanings attached to beliefs and practices on stillbirth or neonatal death among the Lango community in Lira District, Northern Uganda. Participants were sampled purposively for FGD while key informants were identified through snowballing technique. Data were audio recorded in Lango, transcribed, and later translated, a codebook was developed and data entered into Atlas. ti version 8.4.26 and then coded. It was analysed both deductively and inductively into themes.

Results

Stillbirth and early neonatal death both attract similar rituals as would an older child. Burial is not rushed and is attended by family members and close friends. Stillbirths and children that die before naming are buried without names. Bereaved families are comforted and encouraged about future pregnancies. Currently, Lango associates the deaths to biomedical explanations such as teenage pregnancies, inadequate pregnancy care, health system challenges and poor health-seeking behaviour, unlike previously when they were attributed to consequences of unacceptable social behaviours, superstitious beliefs and witchcraft. Antenatal care and health facility childbirths are currently preferred over traditional practices for good pregnancy outcomes.

Conclusion

Stillbirth or early neonatal death is viewed as the death of a child, different from other settings. Thus, rituals are performed to honour, create memory, and maintain the connection with deceased babies. Bereaved parents are supported. Health care workers need to provide culturally sensitive support to parents after perinatal loss. The prevailing beliefs of perinatal death cause in terms of biomedical explanations consistent with known determinants and preference for health facility care for prevention creates an opportunity for improving perinatal health.
Time-dependent recurrence and resolution of pigment epithelial detachment in central serous chorioretinopathy
Authors: Meng Yang , Chen Liao , Li Lu , Xu Yishuang , Su Yu , Zhang Lu , Yi Zuohuizi , Chen Changzheng
Published: April 2023

Background

Cortisol plays a role in the pathogenesis of central serous chorioretinopathy (CSC). CSC patients have abnormal time-dependent changes in cortisol levels. Here we report a rare case of a patient with central serous chorioretinopathy whose pigment epithelial detachment (PED) exhibited time-dependent recurrence and resolution.

Case presentation

A 47-year-old man presented in 2016 for vision loss in the left eye related to recurrent CSC. During follow-up, his PED was observed to resolve spontaneously while he was still in our clinic and recurred the next morning. Such time-dependent changes of the PED were observed in several next follow-ups without any intervention. After excluding possible external factors, the abnormal diurnal variation of cortisol was considered as the internal factor affecting PED.

Conclusions

This is the first article that described the spontaneous time-dependent recurrence and resolution of PED without external interference, where endogenous cortisol may be responsible. Interventions against the abnormal cortisol level might be a potential treatment strategy for CSC. More research is urged to explore the impact of the diurnal change in cortisol levels on eyes with CSC.
Decreased insight, but not self-stigma or belief about medicine, is associated with greater severity of delusions in a sample of long-stay patients with schizophrenia: a cross-sectional study
Authors: Beainy Christina , Haddad Chadia , Fekih-Romdhane Feten , Hallit Souheil , Haddad Georges
Published: April 2023

Background

There are, to date, limited and inconsistent findings concerning the relationship between insight and psychotic symptoms, despite some evidence in favor of the clinical and therapeutic relevance of the insight construct. We aimed to add to the pool of the available data in this area, by examining the correlations between the severity of insight and positive psychotic symptoms (delusions and auditory hallucinations), while accounting for self-stigma and attitudes towards medication, in a sample of long-stay inpatients with schizophrenia.

Methods

A cross-sectional study was conducted at the Psychiatric Hospital of the Cross, between July and October 2021. A total of 82 patients diagnosed with schizophrenia (aged 55.55 ± 10.21 years, 54.9% males) were enrolled. The semi-structured psychotic symptom rating scales, the Birchwood Insight Scale, the Belief About Medicine Questionnaire, and the Internalized Stigma of Mental Illness were used.

Results

The mean duration of illness in years was 30.15 ± 11.73, and the mean duration of hospitalization in years was 17.56 ± 9.24. Sixteen out of the 82 patients (19.5%) were considered as having poor insight. Bivariate analyses showed that higher chlorpromazine equivalent dose was significantly associated with more delusions, whereas higher insight was significantly associated with lower delusions. Multivariable analyses revealed that Higher chlorpromazine equivalent dose (Beta = 0.004) was significantly associated with more delusions, whereas higher insight (Beta = − 0.89) was significantly associated with less delusions. No significant associations were found between insight, self-stigma and hallucinations.

Conclusion

Our results imply that more impaired insight is associated with greater severity of delusions, above and beyond the effects of self-stigma and medication doses. These findings are valuable to aid clinicians and researchers improve their understanding of the relationship insight-psychotic symptoms, and could help personalize prevention and early intervention strategies in schizophrenia.
Comparison of staged LLIF combined with posterior instrumented fusion with posterior instrumented fusion alone for the treatment of adult degenerative lumbar scoliosis with sagittal imbalance
Authors: Lai Oujie , Li Hao , Chen Qixing , Hu Yong , Chen Yunling
Published: April 2023

Background

To retrospectively compare the clinical and radiological outcomes of staged lateral lumbar interbody fusion (LLIF) combined with posterior instrumented fusion(PIF)with PIF alone for the treatment of adult degenerative lumbar scoliosis (ADLS) with sagittal imbalance.

Methods

ADLS patients with sagittal imbalance underwent corrective surgery were included and divided into staged group (underwent multilevel LLIF in the first-stage and PIF in the second-stage) and control group (PIF alone). The clinical and radiological outcomes were evaluated and compared between the two groups.

Results

Forty-five patients with an average age of 69.7±6.3 years were enrolled, including 25 in the staged group and 20 in the control group. Compared with preoperative values, patients in both groups achieved significant improvement in terms of ODI, VAS back, VAS leg and spinopelvic parameters after surgery, which were maintained well during the follow-up period. Compared with control group, total operative time in the staged group was longer, but the amounts of blood loss and blood transfusion were reduced. The average posterior fixation segments were 6.20±1.78 in the staged group and 8.25±1.16 in the control group (P<0.01), respectively. Posterior column osteotomy (PCO) was performed in 9 patients (36%) in the staged group, while PCO and/or pedicle subtraction osteotomy were performed in 15 patients (75%) in the control group (P<0.01). There was no difference in complications between the two groups.

Conclusion

Both surgical strategies were effective for the treatment of ADLS with sagittal imbalance. However, staged treatment was less invasive, which reduced the number of posterior fixation segments and osteotomy requirement.
Construction of a novel digital method for quantitative analysis of occlusal contact and force
Authors: Zhao Zhe , Wang Qing , Li Jiale , Zhou Ming , Tang Kai , Chen Jihua , Wang Fu
Published: April 2023

Background

Occlusal analysis is essential in the dental clinical practice. However, the traditional occlusal analysis performed on the two-dimensional level can not directly correspond to the tooth surface with three-dimensional profile, therefore the clinical guidance value is limited.

Methods

By combining the 3D digital dental models and quantitative data from 2D occlusal contact analysis, this study constructed a novel digital occlusal analysis method. The validity and reliability of DP and SA were verified by comparing the results of occlusal analysis of 22 participants. ICC values for occlusal contact area (OCA) and occlusal contact number (OCN) were tested.

Results

Results confirmed the reliability of the two occlusal analysis methods with ICC values of 0.909 for SAOCA, 0.906 for DPOCA, 0.929 for SAOCN and 0.904 for DPOCN. The Bland-Altman plot, paired t-test (tOCN = 0.691, P > 0.05) and Pearson correlation analysis results (R = 0.68, p < 0.001) verified the validity between SA and DP. Then a novel digital occlusal analysis method was constructed, which not only can locate the occlusion contact and provide the quantitative analysis, but also provide a comprehensive description of the resultant force of each tooth and the component forces on the x-, y- and z-axis.

Conclusions

This new occlusal analysis method can obtain quantitative analysis of occlusal contact including contact area and force information simultaneously, which will provide new impetus and greater help for clinical dental treatment and scientific research.
In situ simulation-based team training and its significance for transfer of learning to clinical practice—A qualitative focus group interview study of anaesthesia personnel
Authors: Finstad Anne Strand , Aase Ingunn , Bjørshol Conrad Arnfinn , Ballangrud Randi
Published: April 2023

Background

Anaesthesia personnel are an integral part of an interprofessional operating room-team; hence, team-based training in non-technical skills (NTS) are important in preventing adverse events. Quite a few studies have been done on interprofessional in situ simulation-based team training (SBTT). However, research on anaesthesia personnel’s experiences and the significance for transfer of learning to clinical practice is limited. The aim of this study is to explore anaesthesia personnel’s experience from interprofessional in situ SBTT in NTS and its significance for transfer of learning to clinical practice.

Methods

Follow-up focus group interviews with anaesthesia personnel, who had taken part in interprofessional in situ SBTT were conducted. A qualitative inductive content analysis was performed.

Results

Anaesthesia personnel experienced that interprofessional in situ SBTT motivated transfer of learning and provided the opportunity to be aware of own practice regarding NTS and teamwork. One main category, ‘interprofessional in situ SBTT as a contributor to enhance anaesthesia practice’ and three generic categories, ‘interprofessional in situ SBTT motivates learning and improves NTS’, ‘realism in SBTT is important for learning outcome’, and ‘SBTT increases the awareness of teamwork’ illustrated their experiences.

Conclusions

Participants in the interprofessional in situ SBTT gained experiences in coping with emotions and demanding situations, which could be significant for transfer of learning essential for clinical practice. Herein communication and decision-making were highlighted as important learning objectives. Furthermore, participants emphasized the importance of realism and fidelity and debriefing in the learning design.
LncRNA H19-rich extracellular vesicles derived from gastric cancer stem cells facilitate tumorigenicity and metastasis via mediating intratumor communication network
Authors: Zhao Hongying , Jiang Rongke , Zhang Chunmei , Feng Zhijing , Wang Xue
Published: April 2023

Background

Extracellular vesicles (EVs) transport biologically active molecules, and represent a recently identified way of intercellular communication. Recent evidence has also reported that EVs shed by cancer stem cells (CSCs) make a significant contribution to carcinogenesis and metastasis. Here, this study aims to explore the possible molecular mechanism of CSCs-EVs in gastric cancer (GC) by mediating intratumor communication network.

Methods

CSCs and non-stem cancer cells (NSCCs) were sorted from GC cells, and EVs were isolated from CSCs. H19 was knocked down in CSCs, and CSCs-EVs or CSCs-EVs containing shRNA-H19 (CSCs-EVs-sh-H19) were co-cultured with NSCCs, followed by evaluation of the malignant behaviors and stemness of NSCCs. Mouse models of GC were established and injected with CSCs-EVs from sh-H19-treated NSCCs in vivo.

Results

CSCs had notable self-renewal and tumorigenic capacity compared with NSCCs. CSCs promoted the malignant behaviors of NSCCs and expression of stemness marker proteins through secretion of EVs. Inhibited secretion of CSCs-EVs curtailed the tumorigenicity and metastasis of NSCCs in vivo. H19 could be delivered by CSCs-EVs into NSCCs. H19 promoted the malignant behaviors of NSCCs and stemness marker protein expression in vitro along with tumorigenicity and liver metastasis in vivo, which was mechanistically associated with activation of the YAP/CDX2 signaling axis.

Conclusion

Taken together, the present study points to the importance of a novel regulatory axis H19/YAP/CDX2 in carcinogenic and metastatic potential of CSCs-EVs in GC, which may be potential targets for anticancer therapy.
Filter exchange imaging with crusher gradient modelling detects increased blood–brain barrier water permeability in response to mild lung infection
Authors: Ohene Yolanda , Harris William J. , Powell Elizabeth , Wycech Nina W. , Smethers Katherine F. , Lasič Samo , South Kieron , Coutts Graham , Sharp Andrew , Lawrence Catherine B. , Boutin Hervé , Parker Geoff J. M. , Parkes Laura M. , Dickie Ben R.
Published: April 2023

Blood–brain barrier (BBB) dysfunction occurs in many brain diseases, and there is increasing evidence to suggest that it is an early process in dementia which may be exacerbated by peripheral infection. Filter-exchange imaging (FEXI) is an MRI technique for measuring trans-membrane water exchange. FEXI data is typically analysed using the apparent exchange rate (AXR) model, yielding estimates of the AXR. Crusher gradients are commonly used to remove unwanted coherence pathways arising from longitudinal storage pulses during the mixing period. We first demonstrate that when using thin slices, as is needed for imaging the rodent brain, crusher gradients result in underestimation of the AXR. To address this, we propose an extended crusher-compensated exchange rate (CCXR) model to account for diffusion-weighting introduced by the crusher gradients, which is able to recover ground truth values of BBB water exchange (kin) in simulated data. When applied to the rat brain, kin estimates obtained using the CCXR model were 3.10 s−1 and 3.49 s−1 compared to AXR estimates of 1.24 s−1 and 0.49 s−1 for slice thicknesses of 4.0 mm and 2.5 mm respectively. We then validated our approach using a clinically relevant Streptococcus pneumoniae lung infection. We observed a significant 70 ± 10% increase in BBB water exchange in rats during active infection (kin = 3.78 ± 0.42 s−1) compared to before infection (kin = 2.72 ± 0.30 s−1; p = 0.02). The BBB water exchange rate during infection was associated with higher levels of plasma von Willebrand factor (VWF), a marker of acute vascular inflammation. We also observed 42% higher expression of perivascular aquaporin-4 (AQP4) in infected animals compared to non-infected controls, while levels of tight junction proteins remain consistent between groups. In summary, we propose a modelling approach for FEXI data which removes the bias in estimated water-exchange rates associated with the use of crusher gradients. Using this approach, we demonstrate the impact of peripheral infection on BBB water exchange, which appears to be mediated by endothelial dysfunction and associated with an increase in perivascular AQP4.
Hyperoxia for accidental hypothermia and increased mortality: a post-hoc analysis of a multicenter prospective observational study
Authors: Yamamoto Ryo , Yoshizawa Jo , Takauji Shuhei , Hayakawa Mineji , Sasaki Junichi
Published: April 2023

Background

Supraphysiologic oxygen administration causes unfavorable clinical outcomes in various diseases, including traumatic brain injury, post–cardiac arrest syndrome, and acute lung injury. Accidental hypothermia is a critical illness that reduces oxygen demands, and excessive oxygen is likely to emerge. This study aimed to determine whether hyperoxia would be associated with increased mortality in patients with accidental hypothermia.

Methods

A post-hoc analysis of a nationwide multicenter prospective observational study (ICE-CRASH study) on patients with accidental hypothermia admitted in 2019–2022 was conducted. Adult patients without cardiac arrest whose core body temperature was < 32 °C and whose arterial partial pressure of oxygen (PaO2) was measured at the emergency department were included. Hyperoxia was defined as a PaO2 level of 300 mmHg or higher, and 28-day mortality was compared between patients with and without hyperoxia before rewarming. Inverse probability weighting (IPW) analyses with propensity scores were performed to adjust patient demographics, comorbidities, etiology and severity of hypothermia, hemodynamic status and laboratories on arrival, and institution characteristics. Subgroup analyses were conducted according to age, chronic cardiopulmonary diseases, hemodynamic instability, and severity of hypothermia.

Results

Of the 338 patients who were eligible for the study, 65 had hyperoxia before rewarming. Patients with hyperoxia had a higher 28-day mortality rate than those without (25 (39.1%) vs. 51 (19.5%); odds ratio (OR) 2.65 (95% confidence interval 1.47–4.78); p < 0.001). IPW analyses with propensity scores revealed similar results (adjusted OR 1.65 (1.14–2.38); p = 0.008). Subgroup analyses showed that hyperoxia was harmful in the elderly and those with cardiopulmonary diseases and severe hypothermia below 28 °C, whereas hyperoxia exposure had no effect on mortality in patients with hemodynamic instability on hospital arrival.

Conclusions

Hyperoxia with PaO2 levels of 300 mmHg or higher before initiating rewarming was associated with increased 28-day mortality in patients with accidental hypothermia. The amount of oxygen to administer to patients with accidental hypothermia should be carefully determined.

Trial Registration: The ICE-CRASH study was registered at the University Hospital Medical Information Network Clinical Trial Registry on April 1, 2019 (UMIN-CTR ID, UMIN000036132).
The putative methyltransferase LaeA regulates mycelium growth and cellulase production in Myceliophthora thermophila
Authors: Zhao Zhen , Gu Shuying , Liu Defei , Liu Dandan , Chen Bingchen , Li Jingen , Tian Chaoguang
Published: April 2023

Background

Filamentous fungi with the ability to use complex carbon sources has been developed as platforms for biochemicals production.Myceliophthora thermophilahas been developed as the cell factory to produce lignocellulolytic enzymes and plant biomass-based biofuels and biochemicals in biorefinery. However, low fungal growth rate and cellulose utilization efficiency are significant barriers to the satisfactory yield and productivity of target products, which needs our further exploration and improvement.

Results

In this study, we comprehensively explored the roles of the putative methyltransferase LaeA in regulating mycelium growth, sugar consumption, and cellulases expression. Deletion oflaeAin thermophile fungusMyceliophthora thermophilaenhanced mycelium growth and glucose consumption significantly. Further exploration of LaeA regulatory network indicated that multiple growth regulatory factors (GRF) Cre-1, Grf-1, Grf-2, and Grf-3, which act as negative repressors of carbon metabolism, were regulated by LaeA in this fungus. We also determined that phosphoenolpyruvate carboxykinase (PCK) is the core node of the metabolic network related to fungal vegetative growth, of which enhancement partially contributed to the elevated sugar consumption and fungal growth of mutant ΔlaeA. Noteworthily, LaeA participated in regulating the expression of cellulase genes and their transcription regulator. ΔlaeAexhibited 30.6% and 5.5% increases in the peak values of extracellular protein and endo-glucanase activity, respectively, as compared to the WT strain. Furthermore, the global histone methylation assays indicated that LaeA is associated with modulating H3K9 methylation levels. The normal function of LaeA on regulating fungal physiology is dependent on methyltransferase activity.

Conclusions

The research presented in this study clarified the function and elucidated the regulatory network of LaeA in the regulation of fungal growth and cellulase production, which will significantly deepen our understanding about the regulation mechanism of LaeA in filamentous fungi and provides the new strategy for improvement the fermentation properties of industrial fungal strain by metabolic engineering.
Co-administration of exercise training and melatonin on the function of diabetic heart tissue: a systematic review and meta-analysis of rodent models
Authors: Rahbarghazi Afshin , Alamdari Karim Azali , Rahbarghazi Reza , Salehi-Pourmehr Hanieh
Published: April 2023

Purpose

Diabetes mellitus (DM), a hyperglycemic condition, occurs due to the failure of insulin secretion and resistance. This study investigated the combined effects of exercise training and melatonin (Mel) on the function of heart tissue in diabetic rodent models.

Methods

A systematic search was conducted in Embase, ProQuest, Cochrane library, Clinicaltrial.gov, WHO, Google Scholar, PubMed, Ovid, Scopus, Web of Science, Ongoing Trials Registers, and Conference Proceedings in July 2022 with no limit of date or language. All trials associated with the effect of Mel and exercise in diabetic rodent models were included. Of the 962 relevant publications, 58 studies met our inclusion criteria as follows; Mel and type 1 DM (16 studies), Mel and type 2 DM (6 studies), exercise and type 1 DM (24 studies), and exercise and type 2 DM (12 studies). Meta-analysis of the data was done using the Mantel Haenszel method.

Results

In most of these studies, antioxidant status and oxidative stress, inflammatory response, apoptosis rate, lipid profiles, and glucose levels were monitored in diabetic heart tissue. According to our findings, both Mel and exercise can improve antioxidant capacity by activating antioxidant enzymes compared to the control diabetic groups (p < 0.05). The levels of pro-inflammatory cytokines, especially TNF-α were reduced in diabetic rodents after being treated with Mel and exercise. Apoptotic changes were diminished in diabetic rodents subjected to the Mel regime and exercise in which p53 levels and the activity of Caspases reached near normal levels (p < 0.05). Based on the data, both Mel and exercise can change the lipid profile in diabetic rodents, especially rats, and close it to near-to-control levels.

Conclusion

These data showed that exercise and Mel can reduce the harmful effects of diabetic conditions on the heart through the regulation of lipid profile, antioxidant capacity, apoptosis, and inflammation.
Low-dose methotrexate-induced renal failure in a patient with ectopic pregnancy: a case report
Authors: Zhang Lili , Liu Chen , Xiao Ling , Liu Yun
Published: April 2023

Background

Methotrexate is an anticancer drug from the antimetabolite class. It is also used in gynecology and obstetrics for the medical treatment of ectopic pregnancies. Low-dose methotrexate-induced adverse toxic effects are rare. We report a case of toxic effect associated with severe renal insufficiency induced by LD-MTX (Low-Dose Methotrexate) for ectopic pregnancy.

Case presentation

A 46-year-old Chinese woman was in an operation for an ectopic pregnancy of tubal interstitial pregnancy. The embryo villus was so little that we were not sure if it was evacuated, then it was followed with 50 mg methotrexate injection of intramuscular adjacent the uterine horn in the operation. 48 hour later after injection the patient presented with renal failure. The personalized genetic testing showed that MTHFR (677C > T) and ABCB1 (3435T > C) were detected. Gradually, the symptoms improved after calcium leucovorin (CF) rescue, continuous renal replacement therapy (CRRT), promoting blood system regeneration, and multiple supportive treatments.

Conclusions

When toxic effects are suspected, detecting the polymorphisms of an MTHFR gene and monitoring MTX concentration in blood could assist us to formulate individualized and active treatments. The management should be multidisciplinary and as much as possible within an intensive care unit.
Human menstrual blood-derived stem cells reverse sorafenib resistance in hepatocellular carcinoma cells through the hyperactivation of mitophagy
Authors: Zhou Sining , Liu Yiming , Zhang Qi , Xu Huikang , Fang Yangxin , Chen Xin , Fu Jiamin , Yuan Yin , Li Yifei , Yuan Li , Xiang Charlie
Published: April 2023

Background

Sorafenib is a first-line drug targeting the RTK-MAPK signalling pathway used to treat advanced hepatocellular carcinoma (HCC). However, tumour cells readily develop sorafenib resistance, limiting long-term therapy with this drug. In our previous study, we found that human menstrual blood-derived stem cells (MenSCs) altered the expression of some sorafenib resistance-associated genes in HCC cells. Therefore, we wanted to further explore the feasibility of MenSC-based combination therapy in treating sorafenib-resistant HCC (HCC-SR) cells.

Methods

The therapeutic efficiency of sorafenib was determined using CCK-8 (Cell Counting Kit-8), Annexin V/PI and clone formation assays in vitro and a xenograft mouse model in vivo. DNA methylation was determined using RT‒PCR and methylated DNA immunoprecipitation (MeDIP). Autophagy was detected by measuring LC3-II degradation and autophagosome maturation. Transmission electron microscopy identified autophagosomes and mitochondria. Physiological functions of mitochondria were assessed by measuring the ATP content, reactive oxygen species (ROS) generation, and mitochondrial membrane potential (MMP).

Results

The tumour suppressor genes BCL2 interacting protein 3 (BNIP3) and BCL2 interacting protein 3 like (BNIP3L) were silenced by promoter methylation and that BNIP3 and BNIP3L levels correlated negatively with sorafenib resistance in HCC-SR cells. Strikingly, MenSCs reversed sorafenib resistance. MenSCs upregulated BNIP3 and BNIP3L expression in HCC-SR cells via tet methylcytosine dioxygenase 2 (TET2)-mediated active demethylation. In HCC-SR cells receiving sorafenib and MenSC combination therapy, pressure from sorafenib and elevated BNIP3 and BNIP3L levels disrupted balanced autophagy. Hyperactivation of mitophagy significantly caused severe mitochondrial dysfunction and eventually led to the autophagic death of HCC-SR cells.

Conclusions

Our research suggests that combining sorafenib and MenSCs may be a potentially new strategy to reverse sorafenib resistance in HCC-SR cells.
Lung development and regeneration: newly defined cell types and progenitor status
Authors: Meng Xiaogao , Cui Guizhong , Peng Guangdun
Published: April 2023

The lung is the most critical organ of the respiratory system supporting gas exchange. Constant interaction with the external environment makes the lung vulnerable to injury. Thus, a deeper understanding of cellular and molecular processes underlying lung development programs and evaluation of progenitor status within the lung is an essential part of lung regenerative medicine. In this review, we aim to discuss the current understanding of lung development process and regenerative capability. We highlight the advances brought by multi-omics approaches, single-cell transcriptome, in particular, that can help us further dissect the cellular player and molecular signaling underlying those processes.
Cultural communication and diversity along the Grand Canal of China: a case study of folk songs in intangible cultural heritage
Authors: Li Lin
Published: April 2023

As a UNESCO World Heritage Site, the Grand Canal of China has a rich intangible cultural heritage along its route. The intangible cultural heritage of folk songs is an important representative. The study of its distribution characteristics and influencing factors is of practical and social significance for promoting the protection and development of intangible cultural heritage in relevant areas and the construction of the Grand Canal Cultural Belt. This paper uses the theories of musicology, geography, sociology, data statistical analysis and spatial analysis to analyze the distribution pattern of intangible cultural heritage items in the Grand Canal basin from the dimensions of geographical space and folk song genre, and from the perspective of natural and social conditions. The results show that the spatial distribution of folk songs in the Grand Canal basin shows a trend of “distribution along the river, two cores and two belts”. Water system, landform and regional culture are the main influencing factors for the formation and dissemination of intangible cultural heritage of folk songs. At the same time, compared with the mountainous areas in western China, the economic and social development and frequent population flow in the Grand Canal basin lead to the diversified and unified musical culture characteristics of folk songs. Finally, this paper proposes the suggestions that the folk songs should be integrated into the local social and economic activities.
Enrichment of miR-17-5p enhances the protective effects of EPC-EXs on vascular and skeletal muscle injury in a diabetic hind limb ischemia model
Authors: Pan Qunwen , Xu Xiaobing , He Wen , Wang Yan , Xiang Zhi , Jin Xiaojuan , Tang Qiong , Zhao Ting , Ma Xiaotang
Published: April 2023

Background/aims

Diabetes mellitus (DM) is highly susceptible to diabetic hind limb ischemia (DHI). MicroRNA (MiR)-17-5p is downregulated in DM and plays a key role in vascular protection. Endothelial progenitor cell (EPC)-released exosomes (EPC-EXs) contribute to vascular protection and ischemic tissue repair by transferring their contained miRs to target cells. Here, we investigated whether miR-17-5p-enriched EPC-EXs (EPC-EXsmiR-17-5p) had conspicuous effects on protecting vascular and skeletal muscle in DHI in vitro and in vivo.

Methods

EPCs transfected with scrambled control or miR-17-5p mimics were used to generate EPC-EXs and EPC-EXsmiR-17-5p. Db/db mice were subjected to hind limb ischemia. After the surgery, EPC-EXs and EPC-EXsmiR-17-5p were injected into the gastrocnemius muscle of the hind limb once every 7 days for 3 weeks. Blood flow, microvessel density, capillary angiogenesis, gastrocnemius muscle weight, structure integrity, and apoptosis in the hind limb were assessed. Vascular endothelial cells (ECs) and myoblast cells (C2C12 cells) were subjected to hypoxia plus high glucose (HG) and cocultured with EPC-EXs and EPC-EXsmiR-17-5p. A bioinformatics assay was used to analyze the potential target gene of miR-17-5p, the levels of SPRED1, PI3K, phosphorylated Akt, cleaved caspase-9 and cleaved caspase-3 were measured, and a PI3K inhibitor (LY294002) was used for pathway analysis.

Results

In the DHI mouse model, miR-17-5p was markedly decreased in hind limb vessels and muscle tissues, and infusion of EPC-EXsmiR-17-5p was more effective than EPC-EXs in increasing miR-17-5p levels, blood flow, microvessel density, and capillary angiogenesis, as well as in promoting muscle weight, force production and structural integrity while reducing apoptosis in gastrocnemius muscle. In Hypoxia plus HG-injured ECs and C2C12 cells, we found that EPC-EXsmiR-17-5p could deliver their carried miR-17-5p into target ECs and C2C12 cells and subsequently downregulate the target protein SPRED1 while increasing the levels of PI3K and phosphorylated Akt. EPC-EXsmiR-17-5p were more effective than EPC-EXs in decreasing apoptosis and necrosis while increasing viability, migration, and tube formation in Hypoxia plus HG-injured ECs and in decreasing apoptosis while increasing viability and myotube formation in C2C12 cells. These effects of EPC-EXsmiR-17-5p could be abolished by a PI3K inhibitor (LY294002).

Conclusion

Our results suggest that miR-17-5p promotes the beneficial effects of EPC-EXs on DHI by protecting vascular ECs and muscle cell functions.