bluuebunny/crossref_metadata_2025 huggingface dataset:
Duration of delayed graft function and its impact on graft outcomes in deceased donor kidney transplantation
Authors: Budhiraja Pooja , Reddy Kunam S , Butterfield Richard J , Jadlowiec Caroline C , Moss Adyr A. , Khamash Hassan A , Kodali Lavanya , Misra Suman S , Heilman Raymond L
Published: April 2022

Background

There is controversy regarding the impact of delayed graft function (DGF) on kidney transplant outcomes. We hypothesize that the duration of DGF, rather than DGF itself, is associated with long-term kidney graft function.

Methods

We analyzed all deceased donor kidney transplants (DDKT) done at our center between 2008 to 2020. We determined factors associated with DGF duration. DGF duration was assessed at three 14-day intervals: < 14 DGF days, 14–27 DGF days, > 28 DGF days.

We studied the impact of DGF duration on survival and graft function and resource utilization, including hospital length of stay and readmissions.

Results

1714 DDKT recipients were included, 59.4% (n = 1018) had DGF. The median DGF duration was 10 days IQR (6,15). The majority of recipients (95%) had resolution of DGF within 28 days. Donor factors associated with DGF days were longer cold ischemia time, donor on inotropes, older age, donation after circulatory death, higher terminal creatinine, and hypertension. Recipient factors associated with increased DGF duration included male sex, length on dialysis before transplant, and higher body mass index. There were no differences in acute rejection events or interstitial fibrosis progression by 4 months when comparing DGF days. The median length of stay was 3 days. However, readmissions increased with increasing DGF duration. Death-censored graft survival was not associated with the length of DGF except when DGF lasted > 28 days.

Conclusions

Inferior graft survival was observed only in recipients of DDKT with DGF lasting beyond 28 days. DGF lasting < 28 days had no impact on graft survival. Duration of DGF, rather than DGF itself, is associated with graft survival.

Trial Registration

Retrospective study approved by Mayo Clinic IRB number ID: 20-011561.
Non-invasive brain stimulation combined with psychosocial intervention for depression: a systematic review and meta-analysis
Authors: He Jiali , Tang Yiling , Lin Jingxia , Faulkner Guy , Tsang Hector W. H. , Chan Sunny H. W.
Published: April 2022

Objectives

This review investigates the efficacy and safety of non-invasive brain stimulation (NIBS) combined with psychosocial intervention on depressive symptoms.

Materials and methods

We systematically searched five electronic databases from their inception to June 2021: PubMed, Embase, PsycINFO, Web of Science, and Medline. Randomized or non-randomized clinical trials in which NIBS plus psychosocial intervention was compared to control conditions in people with depressive symptoms were included.

Results

A total of 17 eligible studies with 660 participants were included. The meta-analysis results showed that NIBS combined with psychosocial therapy had a positive effect on moderate to severe depression ([SMD = − 0.46, 95%CI (− 0.90, − 0.02), I2 = 73%, p < .01]), but did not significantly improve minimal to mild depression ([SMD = − 0.12, 95%CI (− 0.42, 0.18), I2 = 0%, p = .63]). Compared with NIBS alone, the combination treatment had a significantly greater effect in alleviating depressive symptoms ([SMD = − 0.84, 95%CI (− 1.25, − 0.42), I2 = 0%, p = .93]). However, our results suggested that the pooled effect size of ameliorating depression of NIBS plus psychosocial intervention had no significant difference compared with the combination of sham NIBS [SMD = − 0.12, 95%CI (− 0.31, 0.07), I2 = 0%, p = .60] and psychosocial intervention alone [SMD = − 0.97, 95%CI (− 2.32, 0.38), I2 = 72%, p = .01].

Conclusion

NIBS when combined with psychosocial intervention has a significant positive effect in alleviating moderately to severely depressive symptoms. Further well-designed studies of NIBS combined with psychosocial intervention on depression should be carried out to consolidate the conclusions and explore the in-depth underlying mechanism.
“It’s changed my life not to have the continual worry of being warm” – health and wellbeing impacts of a local fuel poverty programme: a mixed-methods evaluation
Authors: Sawyer Alexandra , Sherriff Nigel , Bishop David , Darking Mary , Huber Jörg W.
Published: April 2022

Background

Living in a cold home and being fuel poor can contribute to adverse physical and mental health. Energy efficiency interventions are considered the simplest ways of tackling fuel poverty and preventing associated negative health, wellbeing, and socio-economic consequences. The overall aim of the current study was to provide a greater understanding of the impact of a locally administered programme, which funded the installation of major heating/insulation measures in areas of high fuel poverty, on the health and wellbeing of beneficiaries of the programme.

Methods

A mixed-methods approach to explore the health and wellbeing impacts of a fuel poverty programme in East Sussex that took place between October 2016 and March 2018. Beneficiaries completed the Warwick-Edinburgh Mental Wellbeing Scale before and after any heating/insulation work had been completed in their home. Beneficiaries were also asked to retrospectively rate their health pre- and post-installation. Interviews with 23 beneficiaries of the programme were conducted to explore in-depth the impact of the programme on people’s health and wellbeing and the wider social determinants of health.

Results

A major heating/insulation measure was installed in 149 homes. The majority of measures installed were boilers (57.7%) and new central heating systems (32.2%). Self-rated health and wellbeing were significantly higher post-installation. Interviewees described clear examples of the positive impacts on physical health and wellbeing such as fewer chest infections, reduced pain, feeling less anxious and depressed, and generally feeling happier and more relaxed. Interviews also highlighted broader areas of impact such as reduced social isolation and increased use of domestic space. Many of the beneficiaries also reported a reduction in their energy bills since their new heating systems had been installed.

Conclusions

The findings from the evaluation suggest that the installation of major heating or insulation measures such as new boilers have substantial benefits for the health and wellbeing of beneficiaries. The findings also suggest that the programme had a positive impact on wider determinants of health including reduction in stress and isolation that are likely to be part of the pathways between fuel poverty interventions and mental and physical health outcomes.
Typologies of stress appraisal and problem-focused coping: associations with compliance with public health recommendations during the COVID-19 pandemic
Authors: Landy Justin F. , Shigeto Aya , Laxman Daniel J. , Scheier Lawrence M.
Published: April 2022

Background

Given prior research finding that young adults are less likely to engage in recommended public health behaviors (PHBs) than older adults, understanding who is and is not likely to engage in PHBs among young adults is crucial to mitigating the effects of the COVID-19 pandemic. Drawing on the Transactional Theory of Stress and Coping, this study examined how typologies of stress appraisal (SA) and problem-focused coping (PFC) among young adults were associated with compliance with public health recommendations during the pandemic.

Methods

An online sample of young adults in the United States, ages 18–35, was recruited during the early phase of the pandemic (April–May 2020). Participants reported their appraisals of how central, threatening, and uncontrollable the pandemic was, their tendencies to engage in instrumental, problem-focused coping strategies, and how frequently they engaged in three recommended PHBs (social distancing, mask wearing, and hand washing).

Results

Using latent class analysis, we identified three classes of individuals: Low-SA/Low-PFC, Low-SA/High-PFC, and High-SA/High-PFC. Demographics did not efficiently distinguish membership in the three classes. The former two classes reported less compliance with public health recommendations than did the latter class. Tests of measurement invariance for gender indicated trivial differences in the composition of class membership and relations to compliance.

Conclusions

This research uncovered three qualitatively distinct classes of people who differed in their appraisal of the pandemic and their tendency to engage in PFC. Individuals who view the pandemic as central and threatening and engage in problem-focused coping were more likely than their peers to comply with guidelines recommending social distancing, mask wearing, and hand washing. These results contribute to our understanding of why people do and do not comply with public health guidelines and highlight the importance of attending to psychological variables in public health research. Understanding what drives poor compliance with public health recommendations can contribute to efforts promoting better compliance, and ultimately better health outcomes.
Influencing factors of children’s physical activity in family
Authors: Cai Jie , Zhao Yaping , Wang Jing , Wang Lei
Published: April 2022

Background

Children's physical activity (PA) is an important guarantee for children's physical and mental health. Influencing factors of children's PA in family is related to the healthy growth of children and the happy life of families.

Methods

This is a cross-sectional study of influencing factors of children's PA in family. Parents whose children in 15 kindergartens(i.e., children are aged from 3 to 6 years) were sampled.

Results

Government had a significant negative impact on parents’ perceived risks. Community has a significant positive effect on parents’ perceived benefits and a significant negative effect on parents’ perceived risks. Kindergarten has a significant positive effect on parents’ perceived benefits, but has no significant effect on the parents’ perceived risks. Children sports club has a significant positive effect on parents’ perceived benefits. Parents’ perceived benefits has a significant positive impact on children's PA in family, while perceived risks has a significant negative impact.

Conclusion

Government should play a leading role in the development of children's PA in family. Community provides supplementary support. Kindergarten is the key point of developing children's PA in family. Children sports club is the auxiliary force of children's PA in family.
Granulation tissue-type hemangioma of ureter: a highly misdiagnosed disease (a rare case report and literature review)
Authors: Zhao Jiang , Wang Xiaoqing , Zhang Chi , He Mingze , Bian Ge , Zhang Ming , Liu Mingchuan , Mu Xupeng , Hu Kebang
Published: April 2022

Background

Ureteral granulation tissue hemangiomas are rare benign vascular lesions, and they may be clinically asymptomatic or present with massive or recurrent hematuria. Sometimes hemangiomas are difficult to distinguish from malignant ureteral tumors, and most ureteral hemangiomas are confirmed by postoperative pathological examination. This article aims to present a case of granulation tissue-type hemangioma of the ureter and briefly review the current literature on this condition.

Case presentation

A 30-year-old male patient presented with complaints of painless macroscopic hematuria for 2 months. Computerized tomography of the urinary system showed that the upper 1/3 of the right ureter was occupied, and then the possibility of tumor lesions was considered. The urine cytology showed occasional nuclear abnormalities and many light-stained crystals in urine. Because of suspicious radiological and cytological findings, the patient underwent the right ureteroscopy and the laparoscopic right ureteral mass resection. The postoperative pathological report showed that it was a mesenchymal tumor. The morphological and immunohistochemical staining was consistent with that of hemangioma, tending to granulation tissue hemangioma. After surgery, the patient was in a good state and recovered well at the last follow-up.

Conclusions

Ureteral granulation tissue hemangiomas are an easily misdiagnosed disease. Intermittent painless hematuria is an important characteristic of this disease. Therefore, we suggest that unnecessary radical surgery can be avoided when clinicians consider the possibility of benign ureteral tumors during the evaluation.
Multiparametric transrectal ultrasound for the diagnosis of peripheral zone prostate cancer and clinically significant prostate cancer: novel scoring systems
Authors: Chen Tong , Wang Fei , Chen Hanbing , Wang Meng , Liu Peiqing , Liu Songtao , Zhou Yibin , Ma Qi
Published: April 2022

Background

To evaluate the diagnostic performance of multiparametric transrectal ultrasound (TRUS) and to design diagnostic scoring systems based on four modes of TRUS to predict peripheral zone prostate cancer (PCa) and clinically significant prostate cancer (csPCa).

Methods

A development cohort involved 124 nodules from 116 patients, and a validation cohort involved 72 nodules from 67 patients. Predictors for PCa and csPCa were extracted to construct PCa and csPCa models based on regression analysis of the development cohort. An external validation was performed to assess the performance of models using area under the curve (AUC). Then, PCa and csPCa diagnostic scoring systems were established to predict PCa and csPCa. The diagnostic accuracy was compared between PCa and csPCa scores and PI-RADS V2, using receiver operating characteristics (ROC) and decision curve analysis (DCA).

Results

Regression models were established as follows: PCa = − 8.284 + 4.674 × Margin + 1.707 × Adler grade + 3.072 × Enhancement patterns + 2.544 × SR; csPCa = − 7.201 + 2.680 × Margin + 2.583 × Enhancement patterns + 2.194 × SR. The PCa score ranged from 0 to 6 points, and the csPCa score ranged from 0 to 3 points. A PCa score of 5 or higher and a csPCa score of 3 had the greatest diagnostic performance. In the validation cohort, the AUC for the PCa score and PI-RADS V2 in diagnosing PCa were 0.879 (95% confidence interval [CI] 0.790–0.967) and 0.873 (95%CI 0.778–0.969). For the diagnosis of csPCa, the AUC for the csPCa score and PI-RADS V2 were 0.806 (95%CI 0.700–0.912) and 0.829 (95%CI 0.727–0.931).

Conclusions

The multiparametric TRUS diagnostic scoring systems permitted better identifications of peripheral zone PCa and csPCa, and their performances were comparable to that of PI-RADS V2.
Transurethral plasmakinetic resection versus enucleation for benign prostatic hyperplasia: comparison of intraoperative safety profiles based on endoscopic surgical monitoring system
Authors: Jin Qi , Yang En-Guang , Zhang Yun-Xin , Mi Jun , Dong Zhi-Long , Yang Li , Tian Jun-Qiang , Wang Juan , Wang Zhi-Ping
Published: April 2022

Objective

To compare the intraoperative safety profiles of transurethral plasmakinetic resection of the prostate (PK-TURP) with transurethral plasmakinetic endoscopic enucleation of the prostate (PK-EEP) in the treatment of benign prostatic hyperplasia (BPH) based on endoscopic surgical monitoring system (ESMS).

Methods

A total of 128 patients who were diagnosed with BPH were stratified based on prostate volume (PV) and accepted PK-EEP or PK-TURP treatment at 1:1 ratio. The ESMS as a novel method was used to monitor blood loss and fluid absorption during the operation. Clinical parameters such as intraoperative blood loss volume, fluid absorption volume, operation time, tissue weight of resection, preoperative and postoperative red blood cell count (RBC), hemoglobin concentration (HB), hematocrit (HCT), electrolyte, postoperative bladder irrigation time, indwelling catheter time, hospital stay time and other associated complications were documented and compared between two groups.

Results

No significant differences in majority of baseline characteristics were observed among patients with different prostate volumes between two surgical methods. For patients with prostate volume < 40 ml, the average operation time of patients who received PK-EEP treatment was much more than those who received PK-TURP (P = 0.003). On the other hand, for patients with prostate volume > 40 ml, the PK-TURP surgery was associated with a significant increase in intraoperative blood loss (P = 0.021, in PV 40–80 ml group; P = 0.014, in PV > 80 ml group), fluid absorption (P = 0.011, in PV 40–80 ml group; P = 0.006, in PV > 80 ml group) and postoperative bladder irrigation time as well as indwelling catheter time but decrease in resected tissue weight compared to the PK-EEP treatment.

Conclusion

The ESMS plays an important role in comparison of intraoperative safety profiles between PK-TURP and PK-EEP. Our data suggest that PK-TURP treatment is associated with a decreased operation time in patients with prostate volume < 40 ml and the PK-EEP treatment is associated with decreased intraoperative blood loss, fluid absorption and increased tissue resection for patients with prostate volume > 40 ml. Our results indicate that the size of prostate should be considered when choosing the right operation method.
Risk factors for kidney stone disease recurrence: a comprehensive meta-analysis
Authors: Wang Kai , Ge Jing , Han Wenlong , Wang Dong , Zhao Yinjuan , Shen Yanhao , Chen Jiexun , Chen Dongming , Wu Jing , Shen Ning , Zhu Shuai , Xue Bin , Xu Xianlin
Published: April 2022

Background

Kidney stone disease (KSD) is a common illness that causes an economic burden globally. It is easy for patients to relapse once they have suffered from this disease. The reported recurrence rate of KSD ranged from 6.1% to 66.9%. We performed this meta-analysis to identify various potential risk factors for the recurrence of KSD.

Methods

The PubMed, Embase and Web of Science databases were searched using suitable keywords from inception to Mar 2022. A total of 2,663 records were collected initially. After screening the literature according to the inclusion and exclusion criteria, 53 articles (40 retrospective studies; 13 prospective studies) including 488,130 patients were enrolled. The study protocol was registered with PROSPERO (No. CRD42020171771).

Results

The pooled results indicated that 12 risk factors including younger age (n = 18), higher BMI (n = 16), family history of kidney stones (n = 12), personal history of kidney stones (n = 11), hypertension (n = 5), uric acid stone (n = 4), race of Caucasian (n = 3), suspected kidney stone episode before the first confirmed stone episode (n = 3), surgery (n = 3), any concurrent asymptomatic (nonobstructing) stone (n = 2), pelvic or lower pole kidney stone (n = 2), and 24 h urine test completion (n = 2) were identified to be associated with KSD recurrence. In the subgroup analysis, patients with higher BMI (OR = 1.062), personal history of nephrolithiasis (OR = 1.402), or surgery (OR = 3.178) had a higher risk of radiographic KSD recurrence.

Conclusions

We identified 12 risk factors related to the recurrence of KSD. The results of this analysis could serve to construct recurrence prediction models. It could also supply a basis for preventing the recurrence of KSD.
Tanshinone I attenuates fibrosis in fibrotic kidneys through down-regulation of inhibin beta-A
Authors: Wu Ming , Yang Feng , Huang Di , Ye Chaoyang
Published: April 2022

Background

Tanshinone I (Tan-I), an ingredient of Salvia miltiorrhiza, displays protective effects in several disease models. We aim to study the effect of Tan-I on renal fibrosis and explore its underlining mechanism.

Methods

Rat renal fibroblasts (NRK-49F) were used as an in vitro model to study the effect of Tan-I. Mouse renal fibrosis model was induced by unilateral ureteral obstruction (UUO) or peritoneally injection of aristolochic acid I (AAI).

Results

We found that Tan-I dose-dependently inhibited the expression of pro-fibrotic markers in rat renal fibroblasts. Masson staining and Western blotting analysis showed that Tan-I treatment attenuated renal fibrosis in UUO or AAI induced fibrotic kidneys. RNA sequencing analysis identified inhibin beta-A (INHBA), a ligand of TGF-β superfamily, as a downstream target of Tan-I in fibrotic kidneys, which were further verified by qPCR. Western blotting analysis showed that INHBA is up-regulated in UUO or AAI induced fibrotic kidneys and Tan-I reduced the expression of INHBA in fibrotic kidneys. Inhibition of INHBA by Tan-I was further confirmed in rat fibroblasts. Moreover, knockdown of INHBA reduced the expression of pro-fibrotic markers and abolished the ani-fibrotic effect of Tan-I in rat renal fibroblasts.

Conclusions

We conclude that Tan-I attenuates fibrosis in fibrotic kidneys through inhibition of INHBA.
Telemedicine application in patients with chronic disease: a systematic review and meta-analysis
Authors: Ma Yue , Zhao Chongbo , Zhao Yan , Lu Jiahong , Jiang Hong , Cao Yanpei , Xu Yafang
Published: April 2022

Background

Telemedicine has been widely used for long-term care and self-management in patients with chronic disease, but there is no consensus regarding the effect of telemedicine on chronic disease management. The aim of this study is to review and analyse the effect of telemedicine on the management of chronic diseases such as hypertension, diabetes, and rheumatoid arthritis using a systematic review and meta-analysis.

Methods

We performed a comprehensive literature search of the Web of Science, PubMed, MEDLINE, EMBASE, CNKI (Chinese database), VIP (Chinese database), WanFang (Chinese database), and SinoMed (Chinese database) databases from their inception until December 31, 2021. The retrieved literature was screened and assessed independently by two authors. We used the risk-of-bias assessment tool recommended by the Cochrane Handbook for Systematic Reviews of Interventions 5.0.2 for assessing literature quality and Revman 5.3 software to conduct the meta-analysis.

Results

Fifteen articles were included in this study. The results of the systematic review indicated that telemedicine consultation and telemonitoring are the most commonly used intervention methods. Telemedicine is helpful for improving self-management in patients with rheumatoid arthritis. The results of the meta-analysis showed patients’ index of glycosylated hemoglobin (HbA1c) improved after 12 months of intervention (MD =  − 0.84; 95% CI =  − 1.53, − 0.16; Z = 2.42; P = 0.02), and no significant differences in fasting blood glucose (FBG) levels were observed after 6 months of intervention (MD =  − 0.35; 95% CI =  − 0.75,0.06; Z = 1.69; P = 0.09). The results also showed that systolic blood pressure (MD =  − 6.71; 95% CI =  − 11.40, − 2.02; Z = 2.81; P = 0.005) was reduced after 6 months of intervention.

Conclusion

Telemedicine had a positive effect on the management of diabetes, hypertension, and rheumatoid arthritis, especially when telemedicine consultation and telemonitoring method were used. When telemedicine was used as a disease management tool for patients with diabetes, the optimal intervention time is 12 months. Telemedicine improved the systolic blood pressure in hypertensive patients while also reducing negative emotions and enhancing medication adherence in rheumatoid arthritis patients.
Evaluation of Sampson equation for LDL-C in acute coronary syndrome patients: a Chinese population-based cohort study
Authors: Li Jiayu , Xin Yanguo , Li Jingye , Meng Meng , Zhou Li , Qiu Hui , Chen Hui , Li Hongwei
Published: April 2022

Objective

Low-density lipoprotein cholesterol (LDL-C) is an important cardiovascular disease marker that is used to estimate the risk of acute coronary syndrome in patients. The Sampson equation is an accurate LDL-C equation, but its application in Chinese patients is unclear.

Methods

This study enrolled 12,989 consecutive Chinese patients with the acute coronary syndrome (ACS), LDL-C levels were determined by direct standard method and two indirect equations (Friedewald and Sampson). The detection accuracy and consistency of these two equations were compared in patients classified by triglyceride (TG). In addition, the efficiency of the Sampson equation was also evaluated in patients with different comorbidities.

Results

Patients were divided into six groups according to TG level, and indicated that the Sampson formula was more accurate than the Friedewald formula in all TG spectrums (P < 0.001). The Friedewald formula may underestimate the risk in patients with TG > 400 mg/dL, especially in TG > 800 mg/dL group (r: 0.931 vs. 0.948, 0.666 vs. 0.898, respectively). Compared with the Friedewald equation, the Sampson equation showed more advantages in female, age ≥ 65, body index mass (BMI) < 25, non-smoker, and non-diabetes (0.954 vs. 0.937, 0.956 vs. 0.934, 0.951 vs. 0.939, 0.951 vs. 0.936, and 0.947 vs. 0.938, respectively) than those in male, age < 65, BMI ≥ 25, smoker, and diabetes.

Conclusions

Compared with the Friedewald equation, the Sampson equation is more accurate for LDL-C evaluation in Chinese patients diagnosed with ACS, especially in patients with hypertriglyceridemia even in those with TG > 800 mg/dL. Additionally, the Sampson equation demonstrates greater accuracy even in subgroups of various baseline characteristics and comorbidities.
Mental health and quality of life in different obesity phenotypes: a systematic review
Authors: Abiri Behnaz , Hosseinpanah Farhad , Banihashem Seyedshahab , Madinehzad Seyed Ataollah , Valizadeh Majid
Published: April 2022

Objectives

It has been suggested that obesity phenotypes are related to mental health problems and health-related quality of life (HRQoL). However, there is no certain consensus. This systematic review aimed to evaluate the association between different obesity phenotypes with common psychiatric symptoms and HRQoL.

Methods

Electronic databases i.e. PubMed, Scopus, EMBASE, and google scholar were searched until September 2021, to identify studies that investigated associations between the obesity phenotypes with psychiatric symptoms and/or mental and physical HRQoL. Two researchers independently checked titles and abstracts, evaluated full-text studies, extracted data, and appraised their quality using the Newcastle–Ottawa Scale.

Results

Eighteen studies, with a total of 3,929,203 participants, were included. Of the studies included in this systematic review, 10 articles evaluated the association between obesity phenotypes and psychiatric symptoms, while six papers investigated the association between HRQoL and obesity phenotypes, and two studies assessed both. As a whole, the findings of these studies suggest that obese individuals with a favorable metabolic profile have a slightly higher risk of mental health problems and poor quality of life, however, the risk becomes larger when obesity is combined with an adverse metabolic profile. So, metabolically healthy obesity may not be a completely benign condition in relation to mental disorders and poor quality of life.

Conclusion

According to published research, obesity is likely to increase the risk of mental health problems and poor quality of life when metabolic disturbances are present.
Integrative analysis of therapy resistance and transcriptomic profiling data in glioblastoma cells identifies sensitization vulnerabilities for combined modality radiochemotherapy
Authors: Schnöller Leon Emanuel , Albrecht Valerie , Brix Nikko , Nieto Alexander Edward , Fleischmann Daniel Felix , Niyazi Maximilian , Hess Julia , Belka Claus , Unger Kristian , Lauber Kirsten , Orth Michael
Published: April 2022

Background

Inherent resistance to radio/chemotherapy is one of the major reasons for early recurrence, treatment failure, and dismal prognosis of glioblastoma. Thus, the identification of resistance driving regulators as prognostic and/or predictive markers as well as potential vulnerabilities for combined modality treatment approaches is of pivotal importance.

Methods

We performed an integrative analysis of treatment resistance and DNA damage response regulator expression in a panel of human glioblastoma cell lines. mRNA expression levels of 38 DNA damage response regulators were analyzed by qRT-PCR. Inherent resistance to radiotherapy (single-shot and fractionated mode) and/or temozolomide treatment was assessed by clonogenic survival assays. Resistance scores were extracted by dimensionality reduction and subjected to correlation analyses with the mRNA expression data. Top-hit candidates with positive correlation coefficients were validated by pharmacological inhibition in clonogenic survival assays and DNA repair analyses via residual γH2AX/53BP1-foci staining.

Results

Inherent resistance to single-shot and similarly also to fractionated radiotherapy showed strong positive correlations with mRNA expression levels of known vulnerabilities of GBM, including PARP1, NBN, and BLM, as well as ATR and LIG4—two so far underestimated targets. Inhibition of ATR by AZD-6738 resulted in robust and dose-dependent radiosensitization of glioblastoma cells, whereas LIG4 inhibition by L189 had no noticeable impact. Resistance against temozolomide showed strong positive correlation with mRNA expression levels of MGMT as to be expected. Interestingly, it also correlated with mRNA expression levels of ATM, suggesting a potential role of ATM in the context of temozolomide resistance in glioblastoma cells. ATM inhibition exhibited slight sensitization effects towards temozolomide treatment in MGMT low expressing glioblastoma cells, thus encouraging further characterization.

Conclusions

Here, we describe a systematic approach integrating clonogenic survival data with mRNA expression data of DNA damage response regulators in human glioblastoma cell lines to identify markers of inherent therapy resistance and potential vulnerabilities for targeted sensitization. Our results provide proof-of-concept for the feasibility of this approach, including its limitations. We consider this strategy to be adaptable to other cancer entities as well as other molecular data qualities, and its upscaling potential in terms of model systems and observational data levels deserves further investigation.
Metacell-2: a divide-and-conquer metacell algorithm for scalable scRNA-seq analysis
Authors: Ben-Kiki Oren , Bercovich Akhiad , Lifshitz Aviezer , Tanay Amos
Published: April 2022

Scaling scRNA-seq to profile millions of cells is crucial for constructing high-resolution maps of transcriptional manifolds. Current analysis strategies, in particular dimensionality reduction and two-phase clustering, offer only limited scaling and sensitivity to define such manifolds. We introduce Metacell-2, a recursive divide-and-conquer algorithm allowing efficient decomposition of scRNA-seq datasets of any size into small and cohesive groups of cells called metacells. Metacell-2 improves outlier cell detection and rare cell type identification, as shown with human bone marrow cell atlas and mouse embryonic data. Metacell-2 is implemented over the scanpy framework for easy integration in any analysis pipeline.
Epimutations in both the TESK2 and MMACHC promoters in the Epi-cblC inherited disorder of intracellular metabolism of vitamin B12
Authors: Oussalah Abderrahim , Siblini Youssef , Hergalant Sébastien , Chéry Céline , Rouyer Pierre , Cavicchi Catia , Guerrini Renzo , Morange Pierre-Emmanuel , Trégouët David , Pupavac Mihaela , Watkins David , Pastinen Tomi , Chung Wendy K. , Ficicioglu Can , Feillet François , Froese D. Sean , Baumgartner Matthias R. , Benoist Jean-François , Majewski Jacek , Morrone Amelia , Rosenblatt David S. , Guéant Jean-Louis
Published: April 2022

Background

epi-cblCis a recently discovered inherited disorder of intracellular vitamin B12metabolism associating hematological, neurological, and cardiometabolic outcomes. It is produced by an epimutation at the promoter common toCCDC163PandMMACHC, which results from an aberrant antisense transcription due to splicing mutations in the antisensePRDX1gene neighboringMMACHC. We studied whether the aberrant transcription produced a second epimutation by encompassing the CpG island of theTESK2gene neighboringCCDC163P.

Methods

We unraveled the methylome architecture of theCCDC163P–MMACHCCpG island (CpG:33) and theTESK2CpG island (CpG:51) of 17 epi-cblCcases. We performed an integrative analysis of the DNA methylome profiling, transcriptome reconstruction of RNA-sequencing (RNA-seq), chromatin immunoprecipitation sequencing (ChIP-Seq) of histone H3, and transcription expression ofMMACHCandTESK2.

Results

ThePRDX1splice mutations and activation of numerous cryptic splice sites produced antisense readthrough transcripts encompassing the bidirectionalMMACHC/CCDC163Ppromoter and theTESK2promoter, resulting in the silencing of both theMMACHCandTESK2genes through the deposition of SETD2-dependent H3K36me3 marks and the generation of epimutations in the CpG islands of the two promoters.

Conclusions

The antisense readthrough transcription of the mutatedPRDX1produces an epigenetic silencing ofMMACHCandTESK2. We propose using the term 'epi-digenism' to define this epigenetic disorder that affects two genes. Epi-cblCis an entity that differs fromcblC.Indeed, thePRDX1 and TESK2altered expressions are observed in epi-cblCbut not incblC, suggesting further evaluating the potential consequences on cancer risk and spermatogenesis.
Use of dental drill handpiece to remove steel nut causing penile strangulation: a case report and review of the literature
Authors: Nguyen Tuan Thanh , Ngo Xuan Thai , Chau Quy Thuan , Hoang Khac Chuan , Dinh Le Quy Van , Ly Hoai Tam , Hoang Tien Dat , Dobbs Ryan W. , Thai Minh Sam
Published: April 2022

Background

Penile strangulation is an uncommon urological emergency that requires prompt intervention to avoid potentially serious sequelae including loss of the distal penis secondary to ischemia and subsequent gangrene. We present a case report of a patient who presented to the hospital with penile strangulation injury of 10-hour duration secondary to the presence of a thick hexagonal steel nut. This case is presented in accordance with Consensus Surgical Case Report guidelines.

Case presentation

A 24-year-old Vietnamese man presented to the emergency room with urinary retention and decreased penile sensation following a 10-hour history of penile strangulation due to the presence of a thick hexagonal steel nut that he had placed around the shaft of the penis for the purpose of sexual enhancement during masturbation. The hexagonal nut was tightly entrapping the penile shaft, resulting in edema, congestion, and swelling of the distal 5 cm of the phallus. Given the thickness of the foreign body as well as the degree of penile swelling, we were unable to remove the hexagonal nut using traditional methods of alleviating penile strangulation injuries. Following consultation with a dental colleague, a dental diamond drill handpiece was utilized to cut the foreign body without injury to the underlying penile skin. Subsequent follow-up in clinic demonstrated no significant urinary or sexual sequalae from this episode.

Conclusion

We report a case of penile strangulation requiring novel instrumentation and collaboration for successful treatment.
What evidence exists on the impacts of large herbivores on climate change? A systematic map protocol
Authors: Ramsay Jennifer , Sandom Christopher , Ings Thomas , Wheeler Helen C.
Published: April 2022

Background

In recent years there has been an increased focus on the role of large herbivores in ecosystem restoration and climate change mitigation. There are multiple processes by which large herbivores could potentially influence climate feedback and forcing effects, but the evidence has not yet been synthesised in a systematic and accessible format. Grazing, browsing, trampling, defecation, and seed dispersal by large herbivores can influence vegetation and soils in ways that may directly or indirectly contribute to climate change or mitigation. For example, changes in vegetation could impact wildfire regimes, carbon storage, and albedo, with ultimate impacts on climate. These processes may be influenced by herbivore species composition, density, and functional traits.

The main aim of this systematic map is to synthesise the range of research on climate feedback and forcing effects from large herbivores (≥ 10 kg) in terrestrial ecosystems. We also aim to identify knowledge clusters and gaps in the research base, as well as assessing the potential for quantitative analyses.

Methods

A search of peer-reviewed and grey literature will be conducted using a range of bibliographic databases, search engines and websites. The search strategy will involve using a pre-defined search string with Boolean operators. All search results will be screened for relevance according to specific eligibility criteria. Screening will be conducted in two stages: all articles will initially be screened by title and abstract, then those that meet the eligibility criteria will be screened by full text. At both stages, articles will be excluded if they don’t meet all eligibility criteria or if they meet any exclusion criteria.

All articles included as eligible after full text screening will be coded. At each stage (of screening and coding) a proportion of articles will be processed independently by two reviewers to assess inter-reviewer reliability and resolve differences. The evidence will be presented in a searchable database with accompanying visual outputs. A narrative synthesis will be provided outlining the range and distribution of evidence, knowledge gaps and clusters, potential bias, and areas for further research.
The distribution and density of Huntingtin inclusions across the Huntington disease neocortex: regional correlations with Huntingtin repeat expansion independent of pathologic grade
Authors: Hickman Richard A. , Faust Phyllis L. , Marder Karen , Yamamoto Ai , Vonsattel Jean-Paul
Published: April 2022

Huntington disease is characterized by progressive neurodegeneration, especially of the striatum, and the presence of polyglutamine huntingtin (HTT) inclusions. Although HTT inclusions are most abundant in the neocortex, their neocortical distribution and density in relation to the extent of CAG repeat expansion in the HTT gene and striatal pathologic grade have yet to be formally established. We immunohistochemically studied 65 brains with a pathologic diagnosis of Huntington disease to investigate the cortical distributions and densities of HTT inclusions within the calcarine (BA17), precuneus (BA7), motor (BA4) and prefrontal (BA9) cortices; in 39 of these brains, a p62 immunostain was used for comparison. HTT inclusions predominate in the infragranular cortical layers (layers V-VI) and layer III, however, the densities of HTT inclusions across the human cerebral cortex are not uniform but are instead regionally contingent. The density of HTT and p62 inclusions (intranuclear and extranuclear) in layers V-VI increases caudally to rostrally (BA17 < BA7 < BA4 < BA9) with the median burden of HTT inclusions being 38-fold greater in the prefrontal cortex (BA9) than in the calcarine cortex (BA17). Conversely, intranuclear HTT inclusions prevail in the calcarine cortex irrespective of HTT CAG length. Neocortical HTT inclusion density correlates with CAG repeat expansion, but not with the neuropathologic grade of striatal degeneration (Vonsattel grade) or with the duration of clinical disease since motor onset. Extrapolation of these findings suggest that HTT inclusions are at a regionally-contingent, CAG-dependent, density during the advanced stages of HD. The distribution and density of HTT inclusions in HD therefore does not provide a measure of pathologic disease stage but rather infers the degree of pathogenic HTT expansion.
Thoracic endovascular aortic repair for avulsion of aortic branches in a trauma patient requiring resuscitative thoracotomy: a case report
Authors: Tanikawa Atsushi , Sato Takeaki , Fujita Motoo , Tsuchiya Chieri , Katsuta Ken , Suzuki Yusuke , Kumagai Kiichiro , Saiki Yoshikatsu , Kushimoto Shigeki
Published: April 2022

Background

Resuscitative thoracotomy is a lifesaving procedure for trauma patients that are hemodynamically unstable. Cross-clamping of the descending thoracic aorta is an essential procedure performed during resuscitative thoracotomy in patients with impending cardiac arrest. Although complications related to resuscitative thoracotomy have been reported, there is no report on avulsion of aortic branches related to cross-clamping of the descending aorta and its appropriate management.

Case presentation

We present the case of a 42-year-old woman who sustained blunt trauma due to an accidental fall. The patient was hemodynamically unstable and required resuscitative thoracotomy with cross-clamping of the thoracic aorta. However, hemorrhage from avulsion of aortic branches related to aortic cross-clamping was identified. Initially, transcatheter arterial embolization was attempted to achieve hemostasis; however, when that proved ineffective, thoracic endovascular aortic repair was performed, which resulted in successful hemorrhage control without any sequelae.

Conclusions

Thoracic endovascular aortic repair may be a management option for aortic branch avulsion due to cross-clamping of the descending aorta during resuscitative thoracotomy.
A pilot study investigating the safety and feasibility of endoscopic dilation using a radial incision and cutting technique for benign strictures of the small intestine: a study protocol
Authors: Moroi Rintaro , Shiga Hisashi , Nochioka Kotaro , Shimoyama Yusuke , Kuroha Masatake , Kakuta Yoichi , Kinouchi Yoshitaka , Masamune Atsushi
Published: April 2022

Background

Small benign intestinal stenosis is usually treated by endoscopic balloon dilation (EBD) or surgery. Although EBD and surgery are able to resolve the stenosis in most cases, they are associated with several problems such as insufficient dilation and surgical stress, respectively. On the contrary, a novel approach called radial incision and cutting (RIC) is reported to have several benefits when compared to EBD and surgery. We can currently adopt RIC only for the strictures in the colon or terminal ileum and not for those stenotic lesions present further in the small intestine where balloon-assisted endoscopy is utilized, because the long-type electric knife is currently not approved for use in Japan. We will herein conduct a pilot study to investigate the safety and feasibility of RIC for treating the benign stenoses of the small intestine using the long-type electric knife.

Methods

This will be a single-center, single-arm, interventional trial. The major criteria for inclusion will be age ranging from 20 to 80 years and the presence of benign stenosis in the small intestine. We will perform RIC on 10 participants. The primary outcome is the safety of this procedure, which will be assessed by measuring the frequency of adverse events of special interest. The secondary outcomes will be technical success rate, improvement in subjective symptoms, procedure time, and duration of hospitalization.

Discussion

This pilot study will provide useful information that will aid in adopting RIC for treating the benign strictures present in the small intestine.

Trial registration

jRCT Identifier, jRCTs022200040. Registered on 1 March 2021.
Cloud economy and its relationship with China’s economy—a capital market-based approach
Authors: Lin Lichao , Cheung Adrian
Published: April 2022

Through the lens of the stock market, we examine whether and how the cloud economy affects China’s economy. We review the literature on cloud computing and related concepts and propose a definition of the cloud economy. Based on this new definition, we create a China Cloud Economy Index (CCEI) and its sub-indices. Using stock market data from 2012 to 2020, we analyze the basic characteristics of these indices, their validity, and their relationship with the overall stock market. The robustness of the new index is also examined. We find that the relationship between the CCEI and the stock market had been getting stronger but weakened somewhat after January 11, 2019 plausibly because of the availability of recent cloud-related policies that have widened the gap between the market performance of CCEI and that of the stock market.
Cognitive performance in systemic lupus erythematosus patients: a cross-sectional and longitudinal study
Authors: Langensee L. , Mårtensson J. , Jönsen A. , Zervides K. , Bengtsson A. , Nystedt J. , Cannerfelt B. , Nilsson P. , Mannfolk P. , Lätt J. , Rumetshofer T. , Sundgren P. C.
Published: April 2022

Background

Previous research has provided evidence for cognitive dysfunction as a common symptom of systemic lupus erythematosus (SLE). In light of this, the primary goal of this study was to investigate how cognitive impairment in this patient group develops over time. In addition, the present dataset contributes to delineating the specific abilities that are impaired in SLE patients as well as answering the question whether the disease affects the cognition of SLE patients with neuropsychiatric manifestations (NPSLE) and without (non-NPSLE) in distinct ways.

Methods

91 female participants (33 NPSLE, 29 non-NPSLE, 29 healthy controls (HC)) underwent standardized neurocognitive testing. A total of ten different cognitive abilities were assessed, among others executive function, memory, and attention. Some of the participants (30 NPSLE patients, 22 non-NPSLE, 13 HC) were tested twice (mean time between testing sessions: 50 months) to enable longitudinal tracking of cognitive abilities. Analyses of Variance (ANOVA) were conducted to determine whether cognitive performance differed cross-sectionally between the groups. Linear mixed effects models were fit to investigate performance differences between the groups over time.

Results

Cross-sectional analysis at follow-up demonstrated that the cognitive performance of both NPSLE and non-NPSLE was significantly lower than that of HC for the motor speed and the psychomotor speed domain. Additionally, NPSLE patients performed significantly weaker than HC in the complex attention domain. At the same time, the cross-sectional data did not yield any support for performance differences between NPSLE and non-NPSLE patients. Weak positive correlations between disease duration and psychomotor speed, motor speed and reaction time emerged. A temporal progression of cognitive dysfunction in SLE patients was not confirmed.

Conclusions

Cognitive performance is affected in both non-NPSLE and NPSLE patients. However, a linear decline in performance over time could not be verified. More in-depth longitudinal assessments of cognition in SLE patients are needed to establish how cognitive abilities in this patient population develop over time.
The use of technology in postgraduate medical education within radiology: a scoping review
Authors: Akoob Sakina , Akbar Khalida , Van Wyk Jacqueline
Published: April 2022

Postgraduate radiology training has traditionally followed didactic approaches; however, complex reasoning skills and critical thinking are essential in the field of radiology. Therefore, the shortages of radiologists in Africa have necessitated the need to review the use of technology in postgraduate education to improve efficient training and service. This scoping review was conducted to map the evidence on the role of technology in postgraduate radiology education and practice. A systematic scoping review search strategy was undertaken to review material published between January 2005 and August 2020 on the use of technology in radiology education. Data from the included studies were extracted and analyzed for emerging themes and presented in response to the research question. Seven articles described studies from the African continent. The most popular technological intervention was telemedicine, and several niche areas of technology implementation were identified (blended learning, flipped learning, digital teaching files). Furthermore, the most challenging aspects relating to technology use remain fiscal and credentialing constraints. Technology plays a role in postgraduate radiology education through networks, synchronous and asynchronous applications. It has the potential to increase support to doctoral students in the African context and alleviate some stressors associated with traditional, face-to-face didactic programs.