bluuebunny/crossref_metadata_2025_split huggingface dataset:
The immunometabolite itaconate inhibits heme synthesis and remodels cellular metabolism in erythroid precursors
Authors: Marcero Jason R. , Cox James E. , Bergonia Hector A. , Medlock Amy E. , Phillips John D. , Dailey Harry A. 
Published: September 2021

Abstract
As part of the inflammatory response by macrophages, Irg1 is induced, resulting in millimolar quantities of itaconate being produced. This immunometabolite remodels the macrophage metabolome and acts as an antimicrobial agent when excreted. Itaconate is not synthesized within the erythron but instead may be acquired from central macrophages within the erythroid island. Previously, we reported that itaconate inhibits hemoglobinization of developing erythroid cells. Herein we show that this action is accomplished by inhibition of tetrapyrrole synthesis. In differentiating erythroid precursors, cellular heme and protoporphyrin IX synthesis are reduced by itaconate at an early step in the pathway. In addition, itaconate causes global alterations in cellular metabolite pools, resulting in elevated levels of succinate, 2-hydroxyglutarate, pyruvate, glyoxylate, and intermediates of glycolytic shunts. Itaconate taken up by the developing erythron can be converted to itaconyl–coenzyme A (CoA) by the enzyme succinyl-CoA:glutarate-CoA transferase. Propionyl-CoA, propionyl-carnitine, methylmalonic acid, heptadecanoic acid, and nonanoic acid, as well as the aliphatic amino acids threonine, valine, methionine, and isoleucine, are increased, likely due to the impact of endogenous itaconyl-CoA synthesis. We further show that itaconyl-CoA is a competitive inhibitor of the erythroid-specific 5-aminolevulinate synthase (ALAS2), the first and rate-limiting step in heme synthesis. These findings strongly support our hypothesis that the inhibition of heme synthesis observed in chronic inflammation is mediated not only by iron limitation but also by limitation of tetrapyrrole synthesis at the point of ALAS2 catalysis by itaconate. Thus, we propose that macrophage-derived itaconate promotes anemia during an inflammatory response in the erythroid compartment.
Dasatinib and dexamethasone followed by hematopoietic cell transplantation for adults with Ph-positive ALL
Authors: Wieduwilt Matthew J. , Yin Jun , Wetzler Meir , Uy Geoffrey L. , Powell Bayard L. , Kolitz Jonathan E. , Liedtke Michaela , Stock Wendy , Beumer Jan H. , Mattison Ryan J. , Storrick Elizabeth , Christner Susan M. , Lewis Lionel D. , Devine Steven , Stone Richard M. , Larson Richard A. 
Published: September 2021

AbstractPost-remission strategies after dasatinib-corticosteroid induction in adult Philadelphia chromosome (Ph)–positive acute lymphoblastic leukemia (ALL) are not well studied. We evaluated dasatinib and dexamethasone induction then protocol-defined post-remission therapies, including hematopoietic cell transplantation (HCT). Adults (N = 65) with Ph-positive ALL received dasatinib-dexamethasone induction, methotrexate-based central nervous system (CNS) prophylaxis, reduced-intensity conditioning (RIC) allogeneic HCT, autologous HCT, or chemotherapy alone, and dasatinib-based maintenance. Key end points were disease-free survival (DFS) and overall survival (OS). The median age was 60 years (range, 22-87 years). The complete remission rate was 98.5%. With a median follow-up of 59 months, 5-year DFS and OS were 37% (median, 30 months) and 48% (median, 56 months), respectively. For patients receiving RIC allogeneic HCT, autologous HCT, or chemotherapy, 5-year DFS were 49%, 29%, and 34%, and 5-year OS were 62%, 57%, and 46%, respectively. Complete molecular response rate after CNS prophylaxis was 40%. Relative to the p190 isoform, p210 had shorter DFS (median 10 vs 34 months, P = .002) and OS (median 16 months vs not reached, P = .05). Relapse occurred in 25% of allogeneic HCT, 57% of autologous HCT, and 36% of chemotherapy patients. T315I mutation was detected in 6 of 8 marrow relapses. Dasatinib CNS concentrations were low. Dasatinib-dexamethasone followed by RIC allogeneic HCT, autologous HCT, or chemotherapy was feasible and efficacious, especially with RIC allogeneic HCT. Future studies should address the major causes of failure: T315I mutation, the p210 BCR-ABL1 isoform, and CNS relapse. This study was registered at www.clinicaltrials.gov as #NCT01256398.
Clinical efficacy of bone transport technology in Chinese older patients with infectious bone nonunion after open tibial fracture
Authors: Wen Ying , Liu Peiming , Wang Zhichao , Li Ning 
Published: September 2021

Abstract
Objective
This study was designed for the first time to analyze clinical efficacy of bone transport technology in Chinese older patients with infectious bone nonunion after open tibial fracture.

Methods
This study retrospectively analyzed 220 older patients with infectious bone nonunion after open tibial fracture. There were 110 patients receiving bone transport technology (Group A) and 110 patients receiving membrane induction technique with antibiotic bone cement (Group B).

Results
There were 164 male patients and 56 female patients, with an age range of 65 to 71 years and an average age of 67 ± 1.3 years. Traffic accident, high-fall injury and crush injury account for 45.5, 27.7 and 26.8%, respectively. Age, gender, histories, causes and fracture location had no significant difference between the two groups (P > 0.05 for all). Operation time in the Group A was significantly shorter than that in the Group B (P < 0.05). Linear and positional alignment (70.9 vs. 57.3), American Knee Society knee function score (167.7 ± 14.9 vs. 123.8 ± 15.7), Baird-Jackson ankle function score (89.9 ± 3.5 vs. 78.4 ± 4.9), bone healing index (43.0 ± 2.0 vs. 44.3 ± 3.0) and clinical recovery (8.2 vs. 4.5) of patients in the Group A were significantly better than those in the Group B (P < 0.05 for all). Wound infection in the Group A (7.3%) was significantly less than that in the Group B (16.4%; P < 0.05). There were neither a neurovascular complication nor a recurrence of infection in the two groups.

Conclusion
Bone transport technology achieved better knee and ankle joint function recovery and superior bone healing and clinical efficacy than membrane induction technique with antibiotic bone cement, suggesting that bone transport technique is worthy of extensive promotion to improve clinical condition of older patients with infectious bone nonunion after open tibial fracture.
Efficacy of rituximab in thymoma associated minimal change disease: case report
Authors: El Ouafi Zhour , Mugnier Clovis , Jeannet Robin , Danthu Clément , Duval Marion , Belle Mbou Valère , Touré Fatouma 
Published: September 2021

Abstract
Background
Thymomas have been associated with a broad spectrum of autoimmune diseases. Minimal change disease (MCD) is the most frequent pathological lesion reported. Pathophysiological mechanisms involved in secondary MCD, and linking MCD to thymoma are not yet fully explained, although the hypothesis of T cell dysfunction has been suggested. The fundamental therapeutic principles are steroids and surgical treatment of thymoma, but failures and relapses often require immunosuppressant combinations.

Case presentation
A 62-year-old female was admitted in our unit for a nephrotic syndrome associated with a thymoma. The diagnosis of thymoma associated MCD was confirmed by kidney biopsy. After surgical resection of the thymoma and steroid therapy, no remission was observed. Immunosuppressive therapy was then intensified with introduction of rituximab. Here, we report a steroid-resistant nephrotic syndrome secondary to MCD associated thymoma, which achieved complete remission after rituximab therapy. To the best of our knowledge, this is the first report of the use and efficacy of rituximab therapy in this pathology.

Conclusions
Our case report suggests that primary and secondary MCD may share similar pathophysiological mechanisms. It does not allow us to draw any conclusions about the mechanism of action of rituximab, but we believe this report argues for the safety and efficacy of rituximab use in thymoma-associated MCD, and therefore constitutes a rationale for future studies.
Altered trigeminothalamic spontaneous low-frequency oscillations in migraine without aura: a resting-state fMRI study
Authors: Kim Ye Eun , Kim Min Kyung , Suh Sang-il , Kim Ji Hyun 
Published: September 2021

Abstract
Background
Recent resting-state fMRI studies demonstrated functional dysconnectivity within the central pain matrix in migraineurs. This study aimed to investigate the spatial distribution and amplitude of low-frequency oscillations (LFOs) using fractional amplitude of low-frequency fluctuation (fALFF) analysis in migraine patients without aura, and to examine relationships between regional LFOs and clinical variables.

Methods
Resting-state fMRI data were obtained and preprocessed in 44 migraine patients without aura and 31 matched controls. fALFF was computed according to the original method, z-transformed for standardization, and compared between migraineurs and controls. Correlation analysis between regional fALFF and clinical variables was performed in migraineurs as well.

Results
Compared with controls, migraineurs had significant fALFF increases in bilateral ventral posteromedial (VPM) thalamus and brainstem encompassing rostral ventromedial medulla (RVM) and trigeminocervical complex (TCC). Regional fALFF values of bilateral VPM thalamus and brainstem positively correlated with disease duration, but not with migraine attack frequency or Migraine Disability Assessment Scale score.

Conclusions
We have provided evidence for abnormal LFOs in the brainstem including RVM/TCC and thalamic VPM nucleus in migraine without aura, implicating trigeminothalamic network oscillations in migraine pathophysiology. Our results suggest that enhanced LFO activity may underpin the interictal trigeminothalamic dysrhythmia that could contribute to the impairments of pain transmission and modulation in migraine. Given our finding of increasing fALFF in relation to increasing disease duration, the observed trigeminothalamic dysrhythmia may indicate either an inherent pathology leading to migraine headaches or a consequence of repeated attacks on the brain.
Construction of a survival prediction model for high-and low -grade UTUC after tumor resection based on “SEER database”: a multicenter study
Authors: Wang Mengmeng , Ren Xin , Wang Ge , Sun Xiaomin , Tang Shifeng , Zhang Baogang , Xing Xiaoming , Zhang Wenfeng , Gao Guojun , Du Jing , Zhang Shukun , Liu Lijuan , Zheng Xia , Zhang Zhenkun , Sun Changgang 
Published: September 2021

Abstract
Background
There are differences in survival between high-and low-grade Upper Tract Urothelial Carcinoma (UTUC). Our study aimed to develop a nomogram to predict overall survival (OS) of patients with high- and low-grade UTUC after tumor resection, and to explore the difference between high- and low-grade patients.

Methods
Patients confirmed to have UTUC between 2004 and 2015 were selected from the Surveillance, Epidemiology and End Results (SEER) database. The UTUCs were identified and classified as high- and low-grade, and 1-, 3- and 5-year nomograms were established. The nomogram was then validated using the Chinese multicenter dataset (patients diagnosed in Shandong, China between January 2010 and October 2020).

Results
In the high-grade UTUC patients, nine important factors related to survival after tumor resection were identified to construct nomogram. The C index of training dataset was 0.740 (95% confidence interval [CI]: 0.727–0.754), showing good calibration. The C index of internal validation dataset was 0.729(95% CI:0.707–0.750). On the other hand, Two independent predictors were identified to construct nomogram of low-grade UTUC. The C index was 0.714 (95% CI: 0.671–0.758) for the training set,0.731(95% CI:0.670–0.791) for the internal validation dataset. Encouragingly, the nomogram was clinically useful and had a good discriminative ability to identify patients at high risk.

Conclusion
We constructed a nomogram and a corresponding risk classification system predicting the OS of patients with an initial diagnosis of high-and low-grade UTUC.
Evaluation of educational interventions on eye health for dietetic and pharmacy professions: a pre-post study
Authors: Tang Diana , Dinh Helen , Almansour Hadi , Burlutsky George , Bussing Jocelyn , Eisenhauer Bronwyn , Gopinath Bamini , Flood Victoria M , Saini Bandana 
Published: September 2021

Abstract
Background
We piloted an educational intervention that aimed to enhance awareness about nutrition-age-related macular degeneration (AMD) links among practising and student dietitians then expanded the scope of this intervention to include general eye health, which was delivered to pharmacy students.

Methods
A pilot intervention was conducted in 2019 at the Dietitians Australia Conference (Gold Coast, Australia) where practising and student dietitians underwent a 2-hour small group educational workshop on nutrition and AMD links. Pre-post questionnaires were administered to participants, with voluntary completion of both questionnaires an indicator of consent to participate in the intervention. The primary intervention outcome was a change in AMD-related nutrition knowledge pre-post intervention. A larger intervention was then conducted at the University of Sydney (Sydney, Australia) where pharmacy students underwent a 4-hour educational module to improve general eye health knowledge, as well as student perceptions and attitudes towards a pharmacists’ role in low vision care. Similarly, pre-post questionnaires were administered, with voluntary completion of both questionnaires an indicator of consent to participate in the intervention. The primary intervention outcomes were changes in total knowledge, total perception and total attitude scores pre-post intervention.

Results
(1) Among 10 accredited and 5 student dietitians, there was significant overall knowledge improvement (mean pre-post score: 7.07 ± 1.94 vs. 10.8 ± 1.01, p = 0.001) specifically around appropriate dietary advice, food sources of key AMD-related nutrients, and awareness of supplements. (2) Among 179 second-year pharmacy students enrolled in the ‘Pharmacy Practice’ Unit of Study (Bachelor of Pharmacy, University of Sydney), total eye health knowledge (6.25 ± 1.93 vs. 6.64 ± 2.0; p = 0.011) significantly improved, along with total perception scores (41.54 ± 5.26 vs. 42.45 ± 4.95; p = 0.004). Total attitude scores were not significantly different.

Conclusions
The pilot intervention improved relevant nutrition-AMD knowledge among practising/student dietitians. The modified intervention for pharmacy students also significantly improved general eye health knowledge as well as students’ perception of a pharmacists’ role in low vision care.
‘The best interest of patients, not self-interest’: how clinicians understand altruism
Authors: Sajjad Madiha , Qayyum Shazia , Iltaf Samina , Khan Rehan Ahmed 
Published: September 2021

Abstract
Background
Altruism refers to acting in ‘the best interest of patients, not self-interest’. With an observed discordance between the concept and practice of altruism, and increasing attention to ‘pathologic altruism’, the role of altruism is blurred in present day medical care. In this background, the required balance of altruistic attitude which needs to be fostered in medical students needs clarity. This problem may be best addressed by the practicing clinicians. The objectives of this study were to explore clinicians’ understanding of altruism in the clinical context and to identify the key concepts of altruism which they felt, must be included in clinical practice.

Methods
It was an exploratory qualitative study to identify clinicians’ understanding of altruism and the key practice points for altruism. Online semi-structured interviews were conducted from 18 clinicians through Zoom and transcribed using Otter. Open coding of interview transcripts was done using Atlas ti 8 and grouped by commonalities under sub themes and themes.

Results
The main concepts regarding the clinicians’ understanding of altruism were prioritizing patients’ interest above oneself, favouring patients beyond routine duty and organized team work for practicing altruism. The essential practice areas identified for altruism were finding a balance between altruistic tendency and self/family life, identifying one’s individual capacity for altruism, establishing teamwork for developing a workplace altruistic attitude, and facilitating patients beyond routine duty.

Conclusions
Altruism is an important professionalism attribute for clinicians, however prioritizing patients interest requires a balanced approach so that it is effective and sustainable. Workplace altruistic cultures may be better promoted through organized team-based approach rather than individual efforts.
Impact of COVID-19 lockdown on glycemic control in patients with type 1 and type 2 diabetes mellitus: a systematic review
Authors: Eberle Claudia , Stichling Stefanie 
Published: September 2021

Abstract
Background
In 2019, a new virus known as severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) has emerged. Coronavirus disease 2019 (COVID-19) was classified as a pandemic in a short period of time. In order to reduce the spread of COVID-19, many countries have imposed a lockdown with movement restrictions, social distancing and home confinement, which has affected routine healthcare activities and everyday life. The aim of this systematic review was to examine the impact of the COVID-19 lockdown on glycemic control in patients with type 1 diabetes (T1D) and type 2 diabetes (T2D).

Methods
We systematically identified studies by searching the databases Cochrane Library, MEDLINE via PubMed, Web of Science Core Collection, EMBASE, and CINAHL until April 2021. We included n = 33 observational studies of which n = 25 investigated T1D and n = 8 T2D.

Results
Overall, we analyzed n = 2881 T1D patients and n = 1823 T2D patients. Glycemic values in patients with T1D improved significantly during lockdown. Overall, n = 18 (72%) T1D studies indicated significant improvements in glycemic outcomes. Meta-analysis revealed a mean difference in HbA1c of − 0.05% (95% CI − 0.31 to 0.21) due to lockdown, and in time in range (TIR) of + 3.75% (95% CI 2.56 to 4.92). Lockdown determined a short-term worsening in glycemic values in patients with T2D. Overall, n = 4 (50%) publications observed deteriorations in glycemic control. Meta-analysis demonstrated a mean difference in HbA1c of + 0.14 (95% CI − 0.13 to 0.40) through the lockdown. Moreover, n = 3 (75%) studies reported a not significant deterioration in body weight.

Conclusions
Glycemic values in people with T1D significantly improved during COVID-19 lockdown, which may be associated with positive changes in self-care and digital diabetes management. In contrast, lockdown rather determined a short-term worsening in glycemic parameters in patients with T2D. Further research is required, particularly into the causes and effective T2D management during lockdown.
Thrombosis of the right iliac, femoral, popliteal, and tibial arteries in a post-COVID-19 in adolescent
Authors: da Silva Mariana Orate Menezes , Amorim Santos Henrique , da Silva Amanda Fernandes Vidal , Marum Guilherme , de Godoy Jose Maria Pereira 
Published: September 2021

Abstract
Background
Viral infection into lung, muscular, and endothelial cells results in inflammatory response, including edema, degeneration, and necrotic alterations. The involvement of the major arteries in adolescent with COVID-19 has been infrequently reported in the literature. The aim of the present study is to report thrombosis of the right iliac, femoral and tibial arteries and stenosis of left iliac artery in an adolescent with COVID-19 and to discuss the pathophysiological hypotheses.

Case presentation
We report the case of a 17-year-old female patient with COVID-19 infection. She was seen at the physician specialized general medicine in her hometown, was diagnosed with COVID-19 but did not require hospitalization. After 15 days, she had sudden pain in the left leg that has limited her ability to walk more than 10 met, associated with extremity cyanosis and coldness. Angiotomography revealed thrombosis of a portion of the iliac and popliteal arteries. Na emergency embolectomy was successfully performed, followed by full-dose heparinization with unfractionated heparin.

Conclusion
Arterial thrombosis of large arteries may be associated with chronic inflammatory syndrome secondary to COVID-19 infection and the treatment with a late embolectomy was successful, even in a thrombotic event.
Update on hypnotherapy for psychiatrists
Authors: Chan Natalie A. , Zhang Zhisong , Yin Guoxing , Li Zhimeng , Ho Roger C. 
Published: September 2021

SUMMARYAlthough hypnosis has played a part in psychotherapy for a long time, it is not yet seen as an evidence-based therapy and is absent from many practice guidelines when it comes to the treatment of psychiatric disorders. At present, the applications and methods of hypnotherapy are poorly understood and other methods of psychotherapy tend to be favoured. This review article aims to introduce the role of hypnotherapy and its application for certain common psychiatric presentations, as well as examine its efficacy by summarising recent evidence from high-quality outcome studies and meta-analyses.
Cabozantinib in Combination With Atezolizumab for Advanced Renal Cell Carcinoma: Results From the COSMIC-021 Study
Authors: Pal Sumanta K. , McGregor Bradley , Suárez Cristina , Tsao Che-Kai , Kelly William , Vaishampayan Ulka , Pagliaro Lance , Maughan Benjamin L. , Loriot Yohann , Castellano Daniel , Srinivas Sandy , McKay Rana R. , Dreicer Robert , Hutson Thomas , Dubey Sarita , Werneke Scott , Panneerselvam Ashok , Curran Dominic , Scheffold Christian , Choueiri Toni K. , Agarwal Neeraj 
Published: September 2021

PURPOSE COSMIC-021 is evaluating cabozantinib plus atezolizumab in patients with solid tumors. We report results from patients with advanced clear cell (cc) and non–clear cell (ncc) renal cell carcinoma (RCC). METHODS This phase Ib study ( NCT03170960 ) enrolled patients age ≥ 18 years with advanced RCC. A dose-escalation stage was followed by expansion cohorts. For cohort expansion, prior systemic therapy was not permitted for ccRCC but allowed for nccRCC. Patients received oral cabozantinib 40 mg once a day (ccRCC and nccRCC) or 60 mg once a day (ccRCC only) plus atezolizumab (1,200 mg intravenously, once every 3 weeks). The primary end point was investigator-assessed objective response rate (ORR) per RECIST v1.1; the secondary end point was safety. RESULTS A total of 102 patients were enrolled. Median follow-up was 25.8, 15.3, and 13.3 months for the 40-mg ccRCC, 60-mg ccRCC, and nccRCC groups, respectively. ORR was 53% (80% CI, 41 to 65) in the 40-mg ccRCC group (n = 34) and 58% (80% CI, 46 to 70) in the 60-mg ccRCC group (n = 36), 3% and 11%, respectively, with complete response; median progression-free survival (exploratory end point) was 19.5 and 15.1 months, respectively. In nccRCC (n = 32), ORR was 31% (80% CI, 20 to 44), all partial responses; median progression-free survival was 9.5 months. Grade 3 or 4 treatment-related adverse events (TRAEs) were reported by 71% of patients in the 40-mg ccRCC group, 67% in the 60-mg ccRCC group, and 38% in the nccRCC group; TRAEs leading to discontinuation of both agents occurred in 15%, 6%, and 3% of patients, respectively. There were no grade 5 TRAEs. CONCLUSION The novel combination of cabozantinib plus atezolizumab demonstrated encouraging clinical activity and acceptable tolerability in patients with advanced ccRCC and nccRCC. Disease control was observed across dose levels and histologic subtypes.