bluuebunny/crossref_metadata_2025 huggingface dataset:
Demand without supply? Mass partisanship, ideological attachments, and the puzzle of Guatemala's electoral market failure
Authors: Navia Patricio , Perelló Lucas , Masek Vaclav
Published: January 2022

The demand for an ideologically based party system is not always met with a supply. As a country where a large majority of adults identify on the ideological scale but whose weak political parties primarily function as short-lived personalist platforms, Guatemala represents an extreme case of a demand supply mismatch. Using six AmericasBarometer surveys from 2008 to 2018, we analyze the supply-side (partisanship) and demand-side (ideological identification) effect on voter turnout to identify whether the manifestation of this market failure applies evenly to voters across the ideological scale. We report a nuanced outcome: partisanship and identification on the right of the ideological scale increase turnout, but identification on the center or the left display no significant effect. The absence of parties that effectively represents left-wing or centrist voters—or that at least induce them to turn out to vote—points to a supply-side problem in Guatemala's political representation market.
Clinical validity of the smallest oblique sagittal area of the neural foramen in patients with suspected cervical spondylotic radiculopathy
Authors: Li Jin , Jia Yukun , Qin Yuantian , Peng Zhan , Wang Guangye
Published: January 2022

Objective

To evaluate the smallest oblique sagittal area of the neural foramen in detecting cervical spondylotic radiculopathy (CSR) and to determine its potential significance for treatment decisions.

Methods

The subjects of the study were patients with CSR who visited the spine surgery from 2016 to 2019. All patients were compared according to the minimum oblique sagittal area and the cut-off point value, and they were divided into positive and negative parameters. The changes in neck disability index (NDI), Japanese Orthopaedic Association score (JOA), and visual analog scale (VAS) during the two treatment groups from baseline to at least 24 months of follow-up were compared.

Results

In the surgery group, there was no significant difference in symptom improvement between patients with positive and negative parameters. In the non-surgical group, for patients with positive parameters, NDI decreased by 2.35, JOA increased by 0.88, and neck VAS score improved by 0.42. For patients with negative parameters, NDI decreased by 10.32, JOA increased by 2.86 on average, and neck VAS score improved by 2.46 points on average (both p<0.01 on t test).

Conclusions

Patients with both positive and negative parameters showed significant improvement in their symptoms after surgery, and the smallest oblique sagittal area of the neural foramen seems to be unable to predict the outcome of the surgery. However, in non-surgical patients, symptomatic improvement was more limited in patients with positive parameters than in those with negative parameters. This suggests that patients with positive parameters may be more suitable for surgery and those with negative parameters are more suitable for conservative treatment.
Severe ARDS Secondary to Legionella Pneumonia Requiring VV ECMO in the Setting of Newly Diagnosed Hairy Cell Leukemia
Authors: Gorman Daniel , Green Adam , Puri Nitin , Dellinger Phil
Published: January 2022

Venovenous (VV) extracorporeal membrane oxygenation (ECMO) for severe acute respiratory distress syndrome (ARDS) is initiated in patients with high mortality as a potential lifesaving intervention. Hematologic malignancy (HM) is considered a relative exclusion criterion by the Extracorporeal Life Support Organization (ELSO). This case examines the relative contraindication and presents a successful outcome. A healthy 59-year-old male presented with respiratory distress. On arrival his SpO2 on room air was 82%, chest x-ray revealed a lobar infiltrate, complete blood count demonstrated severe leukopenia, and a peripheral blood smear demonstrated cytoplasmic inclusions concerning for hairy cells. He was intubated and decision was made to initiate VV-ECMO during hospital day (HD) 1. Cytometry later confirmed a diagnosis of hairy cell leukemia (HCL). A diagnosis of Legionella was confirmed on HD 5. Initial hospitalization was complicated by progression to complete bilateral lung involvement, pulmonary hemorrhage, recurrent tachyarrhythmias, hemodynamic instability, and acute renal failure. Respiratory status stabilized and eventually began to improve. On HD 27, he was decannulated and later discharged to rehabilitation. Four months later he received inpatient chemotherapy and is currently in full remission. This is a successful outcome in a patient with severe ARDS requiring VV-ECMO in the setting of newly diagnosed HCL. The 10-year survival for treated HCL is near 100%. Due to favorable prognosis, HCL should not be considered a relative contraindication to VV-ECMO. While HM remains a relative exclusion criterion by the ELSO, it is important to analyze each patient individually and make decisions based on evolving bodies of evidence.
Massive Chylous Ascites After Living Donor Nephrectomy Successfully Treated With Lymphatic Embolization
Authors: Hiffa Anthony , Schulte Kelly , Saeed Muhammad , Gani Imran
Published: January 2022

Chylous ascites may result from a variety of pathological conditions, most of them from nontraumatic causes, such as congenital defects of the lymphatic system, infections, liver cirrhosis, and malignancy. Rarely, chylous ascites occurs as an iatrogenic complication after left-sided laparoscopic donor nephrectomy (LDN). Injury to the cisterna chyli and its main lymphatic tributaries around the para-aortic region intraoperatively can cause the lymphatic fluid to accumulate. There is currently no standardized treatment for chylous ascites as there have only been 54 cases documented to date. Most patients can be managed with conservative therapy. Recommended guidelines include high-protein and low-fat diet with medium-chain triglycerides. Paracentesis is often used as a diagnostic and therapeutic first-line measure with total parenteral nutrition (TPN), bowel rest, and somatostatin analogue as adjunct therapies. We present a case of massive chylous ascites refractory to conservative therapy. The patient had progressive abdominal distention and unintentional weight gain 2 weeks postoperatively warranting multiple paracenteses of >7 L of chylous fluid. Ultimately, the patient was successfully treated with lymphatic embolization using N-butyl cyanoacrylate glue.
Is Teacher–Student and Student–Principal Racial/Ethnic Matching Related to Elementary School Grade Retention?
Authors: Redding Christopher
Published: January 2022

This study uses data from the Early Childhood Longitudinal Study, 2010–2011 to better understand the rates of grade retention during elementary school and the factors associated with this grade retention. Using matched student–teacher and student–principal data, I examine the student-, teacher-, and school-level factors associated with a student’s probability of being retained. I then apply within-student comparisons to examine the extent to which students with a teacher or principal of the same race/ethnicity had a lower probability of being retained. No evidence of a relationship is found between student–teacher and student–principal racial/ethnic matching and reduced grade retention for Black, Latinx, or White students.
Flexible Fixation Technique for Subtle Lisfranc Injuries
Authors: Harlow Ethan R. , Vakharia Ajit M. , Alexeev Mikhail , Miskovsky Shana
Published: January 2022

Background:

Subtle Lisfranc injuries represent a primarily ligamentous Lisfranc complex injury involving the Lisfranc ligament and the medial and middle cuneiform ligaments. Static radiographic displacement or dynamic instability of the medial cuneiform and 2nd metatarsal typically warrants operative intervention to prevent chronic functional pain, allow for timely return-to-sport, and mitigate posttraumatic osteoarthritis. Flexible fixation techniques offer a unique solution to the issues seen with transarticular screws, plates, and arthrodesis for ligamentous Lisfranc injuries.

Indications:

We present the case of a 16-year-old female basketball player with a subtle Lisfranc injury sustained during practice. X-rays show isolated widening of the 1st and 2nd metatarsal bases and dynamic diastasis between the medial and middle cuneiforms. Magnetic resonance imaging (MRI) confirmed a rupture of the plantar Lisfranc ligament. After extensive discussion regarding treatment options, the patient and her family decided to proceed with surgical intervention using a suture anchor and button technique to restore stability to the Lisfranc ligament and intercuneiform complexes.

Technique Description:

A standardized dynamic examination under anesthesia identifies the extent of the injury. Exposure of the base of the 2nd metatarsal and medial cuneiform is performed. Reduction clamps are applied to restore the intercuneiform relationship and interval between the medial cuneiform and base of 2nd metatarsal. The suture anchor and button construct is placed using fluoroscopic guidance. A final dynamic examination is performed to confirm stability of the construct.

Results:

Biomechanical studies have shown that flexible fixation maintains physiologic motion about the Lisfranc articulations and has comparable stability to transarticular screws in cadaveric models of isolated Lisfranc ligament insufficiency. Clinical results are limited but demonstrate excellent postoperative functional outcome scores with very few fixation-related complications at 1 to 3 years.

Discussion:

Flexible fixation techniques for subtle Lisfranc injuries offer unique benefits to transarticular screws, plates, and arthrodesis. We highlight the appropriate evaluation of patients with a suspected subtle ligamentous Lisfranc injury, the surgical technique using a suture button and anchor construct, and review postoperative management and expected outcomes based on the present literature.
Neurofilament light chain serum levels correlate with the severity of neurotoxicity after CAR T-cell treatment
Authors: Schoeberl Florian , Tiedt Steffen , Schmitt Anita , Blumenberg Viktoria , Karschnia Philipp , Burbano Vanessa Granja , Bücklein Veit L. , Rejeski Kai , Schmidt Christian , Busch Galina , von Bergwelt-Baildon Michael , Tonn Jörg-Christian , Schmitt Michael , Subklewe Marion , von Baumgarten Louisa
Published: January 2022

Antitumor therapy with CD19-targeted chimeric antigen receptor (CAR) modified T cells is highly efficient. However, treatment is often complicated by a unique profile of unpredictable neurotoxic adverse effects of varying degrees known as immune effector cell–associated neurotoxicity syndrome (ICANS). We examined 96 patients receiving CAR T cells for refractory B-cell malignancies at 2 major CAR T-cell treatment centers to determine whether serum levels of neurofilament light chain (NfL), a marker of neuroaxonal injury, correlate with the severity of ICANS. Serum NfL levels were measured before and after infusion of CAR T cells using a single-molecule enzyme-linked immunosorbent assay and correlated with the severity of ICANS. Elevated NfL serum levels before treatment were associated with more severe ICANS in both unadjusted and adjusted analyses. Multivariable statistical models revealed a significant increase in NfL levels after CAR T-cell infusion, which correlated with the severity of ICANS. Preexisting neuroaxonal injury. which was characterized by higher NfL levels before CAR T-cell treatment, correlated with the severity of subsequent ICANS. Thus, serum NfL level might serve as a predictive biomarker for assessing the severity of ICANS and for improving patient monitoring after CAR T-cell transfusion. However, these preliminary results should be validated in a larger prospective cohort of patients.
Patient-specific MDS-RS iPSCs define the mis-spliced transcript repertoire and chromatin landscape of SF3B1-mutant HSPCs
Authors: Asimomitis Georgios , Deslauriers André G. , Kotini Andriana G. , Bernard Elsa , Esposito Davide , Olszewska Malgorzata , Spyrou Nikolaos , Arango Ossa Juan , Mortera-Blanco Teresa , Koche Richard , Nannya Yasuhito , Malcovati Luca , Ogawa Seishi , Cazzola Mario , Aaronson Stuart A. , Hellström-Lindberg Eva , Papaemmanuil Elli , Papapetrou Eirini P.
Published: January 2022

SF3B1K700E is the most frequent mutation in myelodysplastic syndrome (MDS), but the mechanisms by which it drives MDS pathogenesis remain unclear. We derived a panel of 18 genetically matched SF3B1K700E- and SF3B1WT-induced pluripotent stem cell (iPSC) lines from patients with MDS with ring sideroblasts (MDS-RS) harboring isolated SF3B1K700E mutations and performed RNA and ATAC sequencing in purified CD34+/CD45+ hematopoietic stem/progenitor cells (HSPCs) derived from them. We developed a novel computational framework integrating splicing with transcript usage and gene expression analyses and derived a SF3B1K700E splicing signature consisting of 59 splicing events linked to 34 genes, which associates with the SF3B1 mutational status of primary MDS patient cells. The chromatin landscape of SF3B1K700E HSPCs showed increased priming toward the megakaryocyte- erythroid lineage. Transcription factor motifs enriched in chromatin regions more accessible in SF3B1K700E cells included, unexpectedly, motifs of the TEA domain (TEAD) transcription factor family. TEAD expression and transcriptional activity were upregulated in SF3B1-mutant iPSC-HSPCs, in support of a Hippo pathway-independent role of TEAD as a potential novel transcriptional regulator of SF3B1K700E cells. This study provides a comprehensive characterization of the transcriptional and chromatin landscape of SF3B1K700E HSPCs and nominates novel mis-spliced genes and transcriptional programs with putative roles in MDS-RS disease biology.
Retrospective observational study of patient outcomes with local wound infusion vs epidural analgesia after open hepato-pancreato-biliary surgery
Authors: Jackson A. C. , Memory K. , Issa E. , Isherwood J. , Graff-Baker P. , Garcea G.
Published: January 2022

Background

Epidural analgesia is conventionally used as the mainstay of analgesia in open abdominal surgery but has a small life-changing risk of complications (epidural abscesses or haematomas). Local wound-infusion could be a viable alternative and are associated with fewer adverse effects.

Methods

A retrospective observational analysis of individuals undergoing open hepato-pancreato-biliary surgery over 1 year was undertaken. Patients either received epidural analgesia (EP) or continuous wound infusion (WI) + IV patient controlled anaesthesisa (PCA) with an intraoperative spinal opiate. Outcomes analyzed included length of stay, commencement of oral diet and opioid use.

Results

Between Jan 2016- Dec 2016, 110 patients were analyzed (WI n=35, EP n=75). The median length of stay (days) was 8 in both the WI and EP group (p=0.846), the median time to commencing oral diet (days) was 3 in WI group and 2 in EP group (p=0.455). There was no significant difference in the amount of oromorph, codeine or tramadol (mg) between WI and EP groups (p=0.829, p=0.531, p=0.073, respectively).

Conclusions

Continuous wound infusion + IV PCA provided adequate analgesia to patients undergoing open hepato-pancreato-biliary surgery. It was non-inferior to epidural analgesia with respect to hospital stay, commencement of oral diet and opioid use.
Association between socio-ecological factors and leisure time physical activity (LTPA) among older adults in Sichuan, China: a structural equation modeling analysis
Authors: Wang Yufei , Li Nanyan , Zhu Jingjie , Deng Qian , Hu Julinling , Xu Jue , Zhou Junmin
Published: January 2022

Background

Few studies examined socio-ecological factors and leisure time physical activities (LTPA) and rarely focused on self-regulation and social capital, which might play a significant role in impacting people’s physical activity behavior. This study aimed to examine the direct and indirect effects of individual level (perceived benefits, perceived barriers, and self-efficacy), interpersonal level (self-regulation), social level (social capital), and environmental level factors (perceived physical environment) on LTPA among older adults.

Methods

A cross-sectional study was conducted in 737 older adults from Sichuan, China. Structural equation modeling (SEM) analysis was used to examine the associations of individual, interpersonal, social, and environmental level factors with LTPA.

Results

The mean age of all participants was 71.22 (range, 60–97), and 56.1% of them were women. The SEM results showed that individual level variables (β = 0.32, ρ < 0.001), self-regulation (β = 0.18, ρ < 0.001) and social capital (β = 0.14, ρ < 0.001) could all directly affect LTPA while there was no significant association of perceived physical environment with LTPA. Self-regulation served as a bridge linking social capital and LTPA. Individual level variables contributed the largest total effect (0.32) on LTPA. Self-regulation and social capital had the same total effect (0.18) on LTPA.

Conclusions

Factors on three levels were all significantly associated with LTPA. Interventions that incorporate individual, interpersonal, social factors may be considered to promote LTPA in older adults. Self-regulation should receive more attention in future interventions.
Association of mass media exposure with combustible and smokeless tobacco use among Indian population: findings from a panel survey
Authors: Paul Ronak , Rashmi Rashmi , Srivastava Shobhit
Published: January 2022

Background

Despite introducing different policies and initiatives, India is recognized as one of the global players in the tobacco epidemic race. Our study explores the association between tobacco consumption and mass media exposure among the Indian population, considering the contextual factors affecting the clustering at the community and state levels.

Methods

Using two waves of the India Human Development Survey (IHDS) conducted in 2005 and 2012 for 16,661 individuals, the present study explores the association of mass media exposure and tobacco consumption in the short-term and the long-term period of Cigarettes and Other Tobacco Products Act (COTPA) implementation, which came into existence in 2004. Bivariate analysis using the chi-square test for association showed the correlation of tobacco consumption with its respective predictors. Multivariable analysis using three-level random intercept logit models showed the adjusted association between tobacco consumption and its relevant covariates and the extent of clustering of tobacco consumption behaviour of persons in the communities and states.

Results

We found that watching television (TV) [(OR:1.03; CI:0.92–1.15) in 2004–05 and (OR:0.99; CI:0.88–1.12) in 2011–12], listening radio [(OR: 0.99; CI:0.90–1.10) in 2004–05 and (OR:1.04; CI:0.94–1.15) in 2011–12] and reading newspaper [(OR:1.02; CI:0.91–1.15) in 2004–05 and (OR:0.96; CI:0.87–1.06) in 2011–12] did not have any significant effect on consumption of combustible tobacco. Similarly, no effect of mass media was found on smokeless tobacco consumption. Further, the clustering of combustible and smokeless tobacco usage was higher at the community level than at the state level. In both rounds, smokeless tobacco consumption was found to be higher than combustible tobacco.

Discussion

The present study provides evidence that COTPA has achieved its aim of nullifying the significant effect of mass media on combustible and smokeless tobacco consumption among the Indian population. However, the influence of state- and community- level clustering had failed in curbing the increment of smokeless tobacco consumption. There is a need for policy reforms to curb the significant impact of factors that promotes smokeless tobacco consumption in India. Further, initiatives must focus on specific communities from high-risk states, reducing the time and cost required for implementation.
3rd generation MICA with the “K-wires-first technique” - a step-by-step instruction and preliminary results
Authors: Toepfer Andreas , Strässle Michael
Published: January 2022

Background

Minimally-invasive techniques for hallux valgus correction are becoming increasingly popular. In the last decades, multiple techniques for minimally-invasive hallux valgus correction have been described. MICA (Minimally-invasive Chevron & Akin), representing the 3rd generation of minimally-invasive hallux valgus correction, combines the advantages of an extraarticular osteotomy, stable internal fixation, and high potential for correction.

This report aims to provide a step-by-step instruction of the surgical technique with the “K-wires-first” MICA modification, illustrated by detailed imaging of both intraoperative fluoroscopy and clinical imaging as well as corresponding sawbone models for each step. Preliminary results including radiological outcome and complications of the first 50 cases will be discussed.

Methods

Between May 2018 and May 2021, 50 consecutive MICAs in 47 patients were performed with theK-wires-first technique. There were 40 women and 7 men with an average of 57.4y (range 25–78). The mean preoperative IMA was 16.2° (range 11.0–21.5), the HVA 30.6° (range 21.8–42.1).

Results

There was one intraoperative conversion to an open surgical bunion correction corresponding to a 2% conversion rate respectively (1/50). On 3 feet (2 patients), removal of the Chevron screws was performed after 7, 9, and 12 months due to prominent and disturbing screw heads at the level of the medial cortex, accounting for a revision rate of 6% (3/50). There were no other secondary revision surgeries. The IMA decreased after MICA by a mean of 10.8° from 16.2° to 5.4° and the HVA by a mean of 22.1° from 30.6° to 8.5°, demonstrating MICA’s high potential for correction.

Conclusions

Compared to other MICA techniques, theK-wires-firstmodification helps to reduce hardware malpositioning and the risk of conversion to open surgery. Furthermore, our preliminary results demonstrate a high potential for correction even for severe hallux deformities.

Trial registration

Retrospectively registered, swissethics BASEC-ID 2021–01537, July 16th, 2021 (www.raps.swissethics.ch).
Online re-examination of postgraduate medical students during the COVID-19 pandemic
Authors: Gu Shixian , Yuan Wenqing , Zhang Aijing , Huo Gang , Jiang Mengyun , Han Jiangli , Shen Ning
Published: January 2022

Background

Postgraduate entrance examination (the Unified National Graduate Entrance Examination) is the major way for Chinese medical undergraduate student to apply for postgraduate studies. It consists of two stages: the preliminary basic written test and the re-examination in form of both written tests and interviews. With the spread of COVID-19, the traditional on-site re-examination of postgraduates must be changed to online re-examination. By comparing the re-examination process and admission results of online and on-site re-examination, we studied the feasibility of online re-examination for postgraduates and measures to improve it.

Methods

This was a retrospective cohort study using data from the Unified National Graduate Entrance Examination. Our sample population was the applicants to Peking University Third Hospital (PUTH) who completed re-examinations. In total, 281 records were successively selected from March 2017 to May 2020. By comparing the re-examination process and admission results of the 2020 online re-examination with those of the 2017-2019 on-site re-examinations, we analyzed the process, difficulties and improvement of online re-examination.

Results

A total of 281 subjects were included, of whom 77.9% completed an on-site re-examination in 2017-2019 and 22.1% completed the 2020 online re-examination. In the on-site re-examinations, 70.8% of the students were admitted, and in the online re-examination, 74.2% of the students were admitted. There were no significant differences between the students who completed on-site and online re-examinations in terms of gender, recent graduation, cultivation type, graduate from a key university, and admission (P>0.05). The on-site and online re-examination results were very similar among the admitted students. The multivariable logistic regression analysis showed that online re-examination had no effect on student admissions. Students seeking professional degree were less likely to be admitted than those seeking academic degree, and those with a better standardized rank in medicine and a better standardized rank of re-examination score were more likely to be admitted.

Conclusions

The online re-examination implemented in 2020 during the COVID-19 pandemic achieved the same selective effect as on-site re-examination. Effective time management, a standardized test question template, well-trained staff and effective technology are the keys to success.
Circulating extracellular vesicles expressing PD1 and PD-L1 predict response and mediate resistance to checkpoint inhibitors immunotherapy in metastatic melanoma
Authors: Serratì Simona , Guida Michele , Di Fonte Roberta , De Summa Simona , Strippoli Sabino , Iacobazzi Rosa Maria , Quarta Alessandra , De Risi Ivana , Guida Gabriella , Paradiso Angelo , Porcelli Letizia , Azzariti Amalia
Published: January 2022

Background

The immunotherapy with immune checkpoints inhibitors (ICI) has changed the life expectancy in metastatic melanoma (MM) patients. Nevertheless, several patients do not respond hence, the identification and validation of novel biomarkers of response to ICI is of crucial importance. Circulating extracellular vesicles (EVs) such as PD-L1+ EV mediate resistance to anti-PD1, instead the role of PD1+ EV is not fully understood.

Methods

We isolated the circulating EVs from the plasma of an observational cohort study of 71 metastatic melanoma patients and correlated the amount of PD-L1+ EVs and PD1+ EVs with the response to ICI. The analysis was performed according to the origin of EVs from the tumor and the immune cells. Subsequently, we analysed the data in a validation cohort of 22 MM patients to assess the reliability of identified EV-based biomarkers. Additionally we assessed the involvement of PD1+ EVs in the seizure of nivolumab and in the perturbation of immune cells-mediated killing of melanoma spheroids.

Results

The level of PD-L1+ EVs released from melanoma and CD8+ T cells and that of PD1+ EVs irrespective of the cellular origin were higher in non-responders. The Kaplan-Meier curves indicated that higher levels of PD1+ EVs were significantly correlated with poorer progression-free survival (PFS) and overall survival (OS). Significant correlations were found for PD-L1+ EVs only when released from melanoma and T cells. The multivariate analysis showed that high level of PD1+ EVs, from T cells and B cells, and high level of PD-L1+ EVs from melanoma cells, are independent biomarkers of response. The reliability of PD-L1+ EVs from melanoma and PD1+ EVs from T cells in predicting PFS was confirmed in the validation cohort through the univariate Cox-hazard regression analysis. Moreover we discovered that the circulating EVs captured nivolumab and reduced the T cells trafficking and tumor spheroids killing.

Conclusion

Our study identified circulating PD1+ EVs as driver of resistance to anti-PD1, and highlighted that the analysis of single EV population by liquid biopsy is a promising tool to stratify MM patients for immunotherapy.
CircMET promotes tumor proliferation by enhancing CDKN2A mRNA decay and upregulating SMAD3
Authors: Yang Lei , Chen Yi , Liu Ning , Lu Yanwen , Ma Wenliang , Yang Zhenhao , Gan Weidong , Li Dongmei
Published: January 2022

Background

Functions of CircMET (hsa_circ_0082002) which is a circular RNA and derived from MET gene remain understood incompletely. In the present study, Xp11.2 translocation/NONO-TFE3 fusion renal cell carcinoma (NONO-TFE3 tRCC) with up-regulated CircMET was employed to investigate its mechanism in cancer progression and post-transcriptional regulation.

Methods

FISH and real-time PCR were performed to explore the expression and localization circMET in NONO-TFE3 tRCC tissues and cells. The functions of circMET in tRCC were investigated by proliferation analysis, EdU staining, colony and sphere formation assay. The regulatory mechanisms among circMET, CDKN2A and SMAD3 were investigated by luciferase assay, RNA immunoprecipitation, RNA pulldown and targeted RNA demethylation system.

Results

The expression of circMET was upregulated by NONO-TFE3 fusion in NONO-TFE3 tRCC tissues and cells, and overexpression of circMET significantly promoted the growth of NONO-TFE3 tRCC. Mechanistic studies revealed that circMET was delivered to cytosol by YTHDC1 in N6-methyladenosine (m6A)-depend manner. CircMET enhances mRNA decay of CDKN2A by direct interaction and recruitment of YTHDF2. Meanwhile, circMET competitively absorbed miR-1197 and prevented those from SMAD3 mRNA.

Conclusions

CircMET promotes the development of NONO-TFE3 tRCC, and the regulation to both CDKN2A and SMAD3 of circMET was revealed. CircMET has the potential to serve as a novel target for the molecular therapy of NONO-TFE3 tRCC as well as the other cancer with high-expressing circMET.
A signature of saliva-derived exosomal small RNAs as predicting biomarker for esophageal carcinoma: a multicenter prospective study
Authors: Li Kai , Lin Yusheng , Luo Yichen , Xiong Xiao , Wang Lu , Durante Kameron , Li Junkuo , Zhou Fuyou , Guo Yi , Chen Shaobin , Chen Yuping , Zhang Dianzheng , Yeung Sai-Ching Jim , Zhang Hao
Published: January 2022

Background

The tRNA-derived small RNAs (tsRNAs) are produced in a nuclease-dependent manner in responses to variety of stresses that are common in cancers. We focus on a cancer-enriched tsRNA signature to develop a salivary exosome-based non-invasive biomarker for human esophageal squamous cell carcinoma (ESCC).

Methods

Cancer-enriched small RNAs were identified by RNA sequencing of salivary exosomes obtained from ESCC patients (n = 3) and healthy controls (n = 3) in a pilot study and further validated in discovery cohort (n = 66). A multicenter prospective observational study was conducted in two ESCC high-incidence regions (n = 320 and 200, respectively) using the newly developed biomarker signature.

Results

The tsRNA (tRNA-GlyGCC-5) and a previously undocumented small RNA were specifically enriched in salivary exosomes of ESCC patients, ESCC tissues and ESCC cells. The bi-signature composed of these small RNAs was able to discriminate ESCC patients from the controls with high sensitivity (90.50%) and specificity (94.20%). Based on the bi-signature Risk Score for Prognosis (RSP), patients with high-RSP have both shorter overall survival (OS) (HR 4.95, 95%CI 2.90–8.46) and progression-free survival (PFS) (HR 3.69, 95%CI 2.24–6.10) than those with low-RSP. In addition, adjuvant therapy improved OS (HR 0.47, 95%CI 0.29–0.77) and PFS (HR 0.36, 95%CI 0.21–0.62) only for patients with high but not low RSP. These findings are consistent in both training and validation cohort.

Conclusions

The tsRNA-based signature not only has the potential for diagnosis and prognosis but also may serve as a pre-operative biomarker to select patients who would benefit from adjuvant therapy.

Trial registration

A prospective study of diagnosis biomarkers of esophageal squamous cell carcinoma, ChiCTR2000031507. Registered 3 April 2016 - Retrospectively registered.
KRAB zinc finger protein ZNF676 controls the transcriptional influence of LTR12-related endogenous retrovirus sequences
Authors: Iouranova Alexandra , Grun Delphine , Rossy Tamara , Duc Julien , Coudray Alexandre , Imbeault Michael , de Tribolet-Hardy Jonas , Turelli Priscilla , Persat Alexandre , Trono Didier
Published: January 2022

Background

Transposable element-embedded regulatory sequences (TEeRS) and their KRAB-containing zinc finger protein (KZFP) controllers are increasingly recognized as modulators of gene expression. We aim to characterize the contribution of this system to gene regulation in early human development and germ cells.

Results

Here, after studying genes driven by the long terminal repeat (LTR) of endogenous retroviruses, we identify the ape-restricted ZNF676 as the sequence-specific repressor of a subset of contemporary LTR12 integrants responsible for a large fraction of transpochimeric gene transcripts (TcGTs) generated during human early embryogenesis. We go on to reveal that the binding of this KZFP correlates with the epigenetic marking of these TEeRS in the germline, and is crucial to the control of genes involved in ciliogenesis/flagellogenesis, a biological process that dates back to the last common ancestor of eukaryotes.

Conclusion

These results illustrate how KZFPs and their TE targets contribute to the evolutionary turnover of transcription networks and participate in the transgenerational inheritance of epigenetic traits.
Activation of TCA cycle restrains virus-metabolic hijacking and viral replication in mouse hepatitis virus-infected cells
Authors: Lee Sang R. , Roh Jeong Yeon , Ryu Jihoon , Shin Hyun-Jin , Hong Eui-Ju
Published: January 2022

Background

One of coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused coronavirus disease 2019 (COVID-19) pandemic and threatened worldwide. However, therapy for COVID-19 has rarely been proven to possess specific efficacy. As the virus relies on host metabolism for its survival, several studies have reported metabolic intervention by SARS-CoV-2.

Results

We investigated the coronavirus-metabolic hijacking using mouse hepatitis virus (MHV) as a surrogate for SARS-CoV-2. Based on the altered host metabolism by MHV infection, an increase of glycolysis with low mitochondrial metabolism, we tried to investigate possible therapeutic molecules which increase the TCA cycle. Endogenous metabolites and metabolic regulators were introduced to restrain viral replication by metabolic intervention. We observed that cells deprived of cellular energy nutrition with low glycolysis strongly suppress viral replication. Furthermore, viral replication was also significantly suppressed by electron transport chain inhibitors which exhaust cellular energy. Apart from glycolysis and ETC, pyruvate supplement suppressed viral replication by the TCA cycle induction. As the non-glucose metabolite, fatty acids supplement decreased viral replication via the TCA cycle. Additionally, as a highly possible therapeutic metabolite, nicotinamide riboside (NR) supplement, which activates the TCA cycle by supplying NAD+, substantially suppressed viral replication.

Conclusions

This study suggests that metabolite-mediated TCA cycle activation suppresses replication of coronavirus and suggests that NR might play a role as a novel therapeutic metabolite for coronavirus.
Adapting systematic scoping study methods to identify cancer-specific physical activity opportunities in Ontario, Canada
Authors: Fong Angela J. , Sabiston Catherine M. , Kauffeldt Kaitlyn D. , Tomasone Jennifer R.
Published: January 2022

Background

Identifying cancer-specific physical activity programs and post-secondary courses targeting students in academic settings (i.e., “real world” opportunities) may promote physical activity behaviors among cancer survivors. Using knowledge synthesis methods such as systematic scoping study methods may facilitate knowledge tool development and guide evidence-based practice to improve knowledge transfer. However, identifying these opportunities poses a challenge as systematic scoping study methods have yet to be applied and adapted to this context. Thus, to extend systematic scoping study methods, the purpose of the current investigation is to describe the adaptation of systematic scoping study methods in the context of cancer-specific “real world” opportunities in Ontario, Canada.

Methods

Systematic scoping study methods were adapted to develop a knowledge tool, which was a credible resource website for researchers, clinicians, and survivors. Three search strategies including Advanced Google Search, targeted website search, and consultations with experts were used to identify eligible (e.g., appropriate for cancer survivors, offered in the community) cancer-specific physical activity programs. Only the targeted website search was used to search post-secondary institutions because they are centralized onto one government website.

Results

Fifty-eight programs and 10 post-secondary courses met the eligibility criteria. Relevant data from these opportunities were extracted, charted, synthesized, and uploaded onto the resource website. The most successful search strategy for cancer-specific physical activity programs was the targeted website search followed by Google Advanced Search and consultations with content experts.

Conclusions

Challenges were experienced due to lack of standard reporting among opportunities, bias of potentially relevant records, and changing nature of resulting records. The current investigation demonstrated that systematic scoping study methods can be applied to cancer-specific physical activity programs and post-secondary courses in the context of cancer survivorship in Ontario yielding robust results. The method can be further adapted and updated in future knowledge syntheses in health-related contexts.

Systematic review registration

The systematic scoping review method protocol has not been registered.
Development of dispersive solid-phase microextraction coupled with high-pressure liquid chromatography for the preconcentration and determination of the selected neonicotinoid insecticides
Authors: Waleng Ngwako Joseas , Selahle Shirley Kholofelo , Mpupa Anele , Nomngongo Philiswa Nosizo
Published: January 2022

Neonicotinoid insecticides have raised a lot of societal concerns due to their environmental ubiquity and unique mode of action. Therefore, it is of great research interest to monitor their occurrence in the environmental waters. However, these compounds exist at low concentrations that is below instrument detection limits. This study reports the applicability of magnetic poly (3 aminobenzoic acid)-based activated carbon (Fe3O4@PABA/AC) composite as an adsorbent in dispersive magnetic solid-phase microextraction (d-MSPME) of neonicotinoid insecticides from wastewater and river water samples. The as-synthesized adsorbent was characterized and confirmed by Fourier transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, Brunauer–Emmett–Teller and X-ray diffraction spectroscopy. The analytes of interest were detected and quantified by high-performance liquid chromatography coupled with diode array detector (HPLC–DAD). The parameters affecting the extraction and preconcentration processes, such as pH, extraction time, mass of adsorbent, desorption time and eluent volume, were optimized using fractional factorial design and central composite design. Under optimum conditions, the limits of detection and quantification were in the ranges of 0.41–0.82 µg L−1 and 1.4–2.7 µg L−1, respectively. The linearity ranged from 1.4–700 µg L−1 with correlation of determination (R2) values varied between 0.9933 and 0.9987. The intra-day and inter-day precisions were 0.35–0.75% and 1.7–5.5%, respectively. The spike recovery experiments were conducted to evaluate the accuracy of the d-MSPME analytical method in real samples, and the percentage recoveries ranged from 86.7 to 99.2%. Therefore, this method shows great potential applicability in preconcentrating the pollutants from the environment.
Analysis of urgent follow up visits and complications after intravitreal injections: a retrospective cohort study
Authors: Miller Alexander , Wilneff Matthew A. , Yazji Andrew , Petrinec Emily , Carbone Michael , Miller Chase , McCrossin Christina , Donkor Richard , Miller David G.
Published: January 2022

Background

Intravitreal injections (IVIs), a common treatment in ophthalmology, result in acute complications and urgent follow-up visits causing significant burden to both patient and physician. We evaluated the incidence of acute complications following IVIs which occurred within seven days of injection.

Methods

A retrospective cohort study conducted at a private retinal practice, in Cleveland, Ohio. Using the practice management software database, we examined 73,286 injections of patients with unscheduled or urgent visits within 7 days of an injection from August 1st,2018 to August 1st,2020. Data collected included: age, gender, eye, medication injected, diagnosis, reason for urgent follow-up, time between injection and urgent follow-up, and type of anesthesia administered. Data was analyzed using SPSS v.28 (SPSS Inc., Chicago IL).

Results

Study included 73,286 injections, with 441 injections (n = 441) resulting in urgent follow-up visits (0.60%). Mean patient age was 72.1 (± 30.4) years, with 187 male (42.4%) and 254 female (57.6%) patients. IVI medications included: aflibercept (60.3%), ranibizumab (22.4%), bevacizumab (13.4%), dexamethasone intravitreal implant (2%), triamcinolone acetonide (1.6%) brolucizumab (1.59%), fluocinolone acetonide intravitreal implant 0.19 mg (0.2%), and fluocinolone acetonide intravitreal implant 0.18 mg (0.03%) (Table 1). Medications associated with urgent visits included: aflibercept (42.9%), bevacizumab (37.4%), ranibizumab (7.9%), dexamethasone intravitreal implant (6.8%), brolucizumab (2.7%), and triamcinolone acetonide (2.3%) (Table 2). Days between injection and urgent follow-up was on average 3.96 ± 2.14 days. Urgent follow-ups included blurred vision in 164 patients (37.2% of urgent visits), flashes, floaters or posterior vitreous detachment (PVD) in 55 (12.5%), pain in 42 (9.5%), 43 (9.8%) corneal abrasions, 33 (7.5%) subconjunctival hemorrhages, corneal dryness or foreign body sensation in 30 (6.6%), endophthalmitis in 20 (4.5%), 18 (4.1%)vitreous hemorrhages, iritis or uveitis in 11 (2.5%), miscellaneous complications in 9 (2.0%), 7 (1.6%) elevated intraocular pressures, choroidal neovascular membrane in 4 (0.9%), 4 (0.9%) retinal detachments or tears, and 2 (0.45%) traumatic cataracts (Table 3).

Conclusion

IVIs resulted in 0.60% urgent/unscheduled follow-up visits within 7 days of injection. Most common causes were blurred vision and symptoms of PVD.
Factors that influence psychiatric trainees’ choice of higher training specialty: mixed-methods study
Authors: Wolstenholme Nicholas , McKinnon Iain , Lloyd Adrian J.
Published: January 2022

Aims and method

Factors influencing trainees’ decisions about choosing and remaining in higher training subspecialties have not been widely researched. We administered telephone questionnaires to higher specialist trainees in the north-east of England to ascertain what influences these decisions. Thematic analysis was employed to develop overall constructs.

Results

Twenty-seven trainees were interviewed, resulting in six overall constructs. These were: supervisory experiences; perceived work–life balance; career prospects; training and working environments; interest in the chosen subspecialty; and previous experience within the chosen subspecialty. Most trainees interviewed felt they had made the right specialty choice.

Clinical implications

This study demonstrates the particular importance of exposure to a specialty and perceptions of the supervisory experience in determining trainees’ choices of, and decisions to remain in, a particular psychiatric specialty. Factors highlighted in this study must inform training, recruitment and workforce planning in order to bolster the recruitment and retention of trainees into higher specialty training.
Use of Adjuvant Bisphosphonates and Other Bone-Modifying Agents in Breast Cancer: ASCO-OH (CCO) Guideline Update
Authors: Eisen Andrea , Somerfield Mark R. , Accordino Melissa K. , Blanchette Phillip S. , Clemons Mark J. , Dhesy-Thind Sukhbinder , Dillmon Melissa S. , D'Oronzo Stella , Fletcher Glenn G. , Frank Elizabeth S. , Hallmeyer Sigrun , Makhoul Issam , Moy Beverly , Thawer Alia , Wu Joy Y. , Van Poznak Catherine H.
Published: January 2022

PURPOSE

To update recommendations of the American Society of Clinical Oncology (ASCO)-Ontario Health (Cancer Care Ontario [CCO]) adjuvant bone-modifying agents in breast cancer guideline.

METHODS

An Expert Panel conducted a systematic review to identify new, potentially practice-changing data.

RESULTS

Four articles met eligibility criteria and form the evidentiary basis for revision of the previous recommendations.

RECOMMENDATIONS

Adjuvant bisphosphonate therapy should be discussed with all postmenopausal patients (natural or therapy-induced) with primary breast cancer, irrespective of hormone receptor status and human epidermal growth factor receptor 2 status, who are candidates to receive adjuvant systemic therapy. Adjuvant bisphosphonates, if used, are not substitutes for standard anticancer modalities. The benefit of adjuvant bisphosphonate therapy will vary depending on the underlying risk of recurrence and is associated with a modest improvement in overall survival. The NHS PREDICT tool provides estimates of the benefit of adjuvant bisphosphonate therapy and may aid in decision making. Factors influencing the decision to recommend adjuvant bisphosphonate use should include patients' risk of recurrence, risk of side effects, financial toxicity, drug availability, patient preferences, comorbidities, and life expectancy. When an adjuvant bisphosphonate is used to prevent breast cancer recurrence, the therapeutic options recommended by the Panel include oral clodronate, oral ibandronate, and intravenous zoledronic acid. The Panel supports starting bisphosphonate therapy early, consistent with the points outlined in the parent CCO-ASCO guideline; this is a consensus recommendation. The Panel does not recommend adjuvant denosumab to prevent breast cancer recurrence, because studies did not show a consistent reduction of breast cancer recurrence in any subset of those with early-stage breast cancer. Additional information can be found at www.asco.org/breast-cancer-guideline .
A Case of Infantile Alagille Syndrome With Severe Dyslipidemia: New Insight into Lipid Metabolism and Therapeutics
Authors: Nakajima Hisakazu , Tsuma Yusuke , Fukuhara Shota , Kodo Kazuki
Published: January 2022

Alagille syndrome (AGS) is an autosomal dominant genetic disorder characterized by congenital heart disease, hepatic cholestasis, dyslipidemia, and characteristic facies since infancy. Cholestatic hypercholesterolemia in patients diagnosed with AGS is occasionally refractory and resistant to conventional treatments. We report the case of a 4-month-old boy diagnosed with AGS and refractory dyslipidemia due to cholestatic liver disease. He had repeated episodes of cyanosis due to pulmonary artery atresia since birth and underwent a Blalock-Taussig shunt procedure at age 3 months. At age 4 months, cholestatic hyperbilirubinemia deteriorated to a serum total bilirubin level of 19.9 mg/dL. At age 12 months, a laboratory test revealed severe dyslipidemia (serum total cholesterol, 1796 mg/dL; serum triglycerides [TGs], 635 mg/dL), and the presence of xanthomas. A pathogenic variant of the JAG1 gene (c.1326G > A, p.Trp442X) was detected through genetic testing. Oral ursodeoxycholate normalized hyperbilirubinemia with a subtle improvement in dyslipidemia. Combination therapy with pravastatin and fenofibrate did not successfully improve dyslipidemia. At age 20 months, altering pravastatin to atorvastatin was effective in normalizing serum cholesterol and TGs with no adverse events.

Combination therapy with atorvastatin and fenofibrate was successful in improving refractory dyslipidemia in a child with AGS. Atorvastatin is a well-known strong statin that can lower serum cholesterol, and fenofibrate can lower serum TG levels. We propose that atorvastatin be taken into consideration for the treatment of persistent hyperlipidemia in patients diagnosed with AGS, because atorvastatin upregulates bile acid synthesis and lipoprotein scavenging, and inhibits intrinsic cholesterol production.