bluuebunny/crossref_metadata_2025_split huggingface dataset:
Teaching pain management to health professional students: A systematic review and meta-analysis
Authors: Ashton Simon , Kilby Matthew , Wu Joey , Lo Kristin 
Published: February 2022

Background Satisfactory pain management can have a significant impact on clients’ activities of daily living. We questioned what types of pain management education might improve health professional students’ knowledge, skills and perceptions? Method From inception until 30th July 2020, we searched MEDLINE, EBM Reviews, CINAHL Plus, ERIC, EMBASE, Cochrane database and Monash University library. Inclusion criteria were controlled trials of health professional students’ pain education compared to alternative education, usual curriculum or no intervention. Studies were limited to English. Data were synthesised using meta-analysis. Results Fourteen articles were included in this review. For continuous data, meta-analysis demonstrated a clear effect favouring the intervention for knowledge SMD 1.47 [95% CI 1.18, 1.77], skills 0.93 [0.58, 1.28] or perceptions 0.69 [0.31, 1.08]. For dichotomous data, results showed no effect for knowledge 4.21 [0.65, 27.41], skills 2.26 [0.47, 11.01] or perceptions 1.96 [0.66, 5.76]. However, the overall result showed an effect 2.82 [1.20, 6.59] favouring the intervention. Conclusions In summary, short theoretical interventions are sufficient to change students’ knowledge and perceptions. Longer interventions incorporating interactivity improve skills. Further research is required to indicate the best method, outcome measure, length of intervention and follow-up in delivering these pain courses and assessing the cost and long-term retention of information.
MR- safety: Evaluation of compliance with screening routines using a structured screening interview
Authors: Hansson Boel , Simic Matea , Olsrud Johan , Markenroth Bloch Karin , Owman Titti , Sundgren Pia C , Björkman-Burtscher Isabella M 
Published: February 2022

Background Magnetic resonance (MR) safety procedures are designed to allow patients, research subjects and personnel to enter the MR-scanner room under controlled conditions and without the risk to be harmed during the examination. Ferromagnetic objects in the MR-environment or inside the human body represent the main safety risks potentially leading to human injuries. Screening for MR-safety risks with dedicated procedures is therefore mandatory. As human errors during the screening procedure might align and lead to an incident compliance is essential. Purpose To evaluate compliance with a documented structured MR-safety screening process. Method Written and signed MR-safety screening documentation collected at a national 7T MR facility during a four-year period was evaluated for compliance of trained personnel with multi-step MR-safety routines. We analysed whether examinations were performed or why they were not performed. Data analysis further included descriptive statistics of the study population (age, gender and patient or healthy volunteer status), identification of missing documents and omitted or incorrect answers, and whether these compliance shortcomings concerned predominantly administrative or MR-safety related issues. Results Documentation of the screening process in 1819 subjects was incomplete in 19% of subjects. The most common documentation shortcoming was omitted fields. Out of 478 omitted answer-fields in 307 subjects, 36% were of administrative nature and 64% related directly to MR-safety issues. Conclusion Compliance with MR-safety screening procedures cannot be taken for granted and deficiencies to comply with screening routines were revealed. Documentation shortcomings concerned both administrative and MR-safety related issues.
Obinutuzumab (GA-101), ibrutinib, and venetoclax (GIVe) frontline treatment for high-risk chronic lymphocytic leukemia
Authors: Huber Henriette , Edenhofer Simone , von Tresckow Julia , Robrecht Sandra , Zhang Can , Tausch Eugen , Schneider Christof , Bloehdorn Johannes , Fürstenau Moritz , Dreger Peter , Ritgen Matthias , Illmer Thomas , Illert Anna L. , Dürig Jan , Böttcher Sebastian , Niemann Carsten U. , Kneba Michael , Fink Anna-Maria , Fischer Kirsten , Döhner Hartmut , Hallek Michael , Eichhorst Barbara , Stilgenbauer Stephan 
Published: February 2022

Abstract
Despite considerable treatment advances with targeted therapies for patients with chronic lymphocytic leukemia (CLL) deemed high-risk [del(17p) and/or TP53 mutation], the outcome is still inferior compared with other CLL patients. Combining multiple agents with distinct mechanisms of action may further improve outcomes. CLL2-GIVe is an open-label, multicenter trial which enrolled patients with previously untreated CLL with del(17p) and/or TP53 mutation. Patients received induction therapy with obinutuzumab (GA-101), ibrutinib, and venetoclax (GIVe) for cycles 1 through 6 and consolidation therapy with venetoclax and ibrutinib for cycles 7 through 12. Ibrutinib monotherapy was continued for cycles 13 through 36 in patients not reaching a complete response (CR) with serial undetectable minimal residual disease (uMRD) after consolidation. The primary endpoint was CR rate at cycle 15 (final restaging). Secondary endpoints included MRD, survival, and safety. All 41 patients enrolled between September 2016 and August 2018 received study treatment and were included in efficacy and safety populations. With a CR rate of 58.5% at cycle 15, the primary endpoint was met (95% CI: 42.1-73.7; P &lt; .001). At final restaging, 78.0% of patients had uMRD in peripheral blood (PB); 65.9% of patients had uMRD in bone marrow (BM). Estimated progression-free survival (PFS) and overall survival (OS) rates at 24 months were both 95.1%. Adverse events were reported in all patients; most were low grade (grade ≥3: 23.9%). Two deaths were reported (cardiac failure and ovarian carcinoma), neither related to study treatment. The CLL2-GIVe treatment regimen has a manageable safety profile and is a first-line treatment of good efficacy for patients with high-risk CLL.
Deletion of Y chromosome before allogeneic hematopoietic stem cell transplantation in male recipients with female donors
Authors: Tamaki Masaharu , Kameda Kazuaki , Kimura Shun-ichi , Harada Naonori , Uchida Naoyuki , Doki Noriko , Tanaka Masatsugu , Ikegame Kazuhiro , Sawa Masashi , Katayama Yuta , Miyakoshi Shigesaburo , Ara Takahide , Kanda Junya , Onizuka Makoto , Fukuda Takahiro , Atsuta Yoshiko , Kanda Yoshinobu , Yakushijin Kimikazu , Nakasone Hideki 
Published: February 2022

Abstract
The graft-versus-leukemia (GVL) effect is one of the curative mechanisms of allogeneic hematopoietic stem cell transplantation (allo-HCT). H-Y antigens, which are encoded by Y chromosome, are important targets of the GVL effect. Thus, deletion of the Y chromosome (del[Y]) might cause the GVL effect to deteriorate in a transplantation involving a female donor and male recipient, although the clinical significance of the del(Y) group remains to be elucidated. In this study, we evaluated adult male patients who underwent allo-HCT between 2010 and 2019 in Japan. There were 155 cases in the del(Y) group and 4149 cases without del(Y) who underwent female-to-male allo-HCT. Del(Y) was significantly associated with inferior overall survival (hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.00-1.53; P = .049) and an increased risk of relapse (HR, 1.40; 95% CI, 1.08-1.80; P = .0098) in multivariate analyses. There was no significant difference in nonrelapse mortality between recipients with and without del(Y) (HR, 1.08; 95% CI, 0.769-1.51; P = .67). In contrast, del(Y) was not significantly associated with any clinical outcomes in the cohort of male-to-male allo-HCT. A higher incidence of relapse might have been caused by attenuation of the GVL effect resulting from a lack of H-Y antigens. Because a GVL effect resulting from sex mismatch may not be expected in men with del(Y) who undergo allo-HCT with a female donor, additional post–allo-HCT strategies might be required to prevent disease relapse.
The roles of Eph receptors, neuropilin-1, P2X7, and CD147 in COVID-19-associated neurodegenerative diseases: inflammasome and JaK inhibitors as potential promising therapies
Authors: Zalpoor Hamidreza , Akbari Abdullatif , Samei Azam , Forghaniesfidvajani Razieh , Kamali Monireh , Afzalnia Azadeh , Manshouri Shirin , Heidari Fatemeh , Pornour Majid , Khoshmirsafa Majid , Aazami Hossein , Seif Farhad 
Published: February 2022

AbstractThe novel coronavirus disease 2019 (COVID-19) pandemic has spread worldwide, and finding a safe therapeutic strategy and effective vaccine is critical to overcoming severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, elucidation of pathogenesis mechanisms, especially entry routes of SARS-CoV-2 may help propose antiviral drugs and novel vaccines. Several receptors have been demonstrated for the interaction of spike (S) protein of SARS-CoV-2 with host cells, including angiotensin-converting enzyme (ACE2), ephrin ligands and Eph receptors, neuropilin 1 (NRP-1), P2X7, and CD147. The expression of these entry receptors in the central nervous system (CNS) may make the CNS prone to SARS-CoV-2 invasion, leading to neurodegenerative diseases. The present review provides potential pathological mechanisms of SARS-CoV-2 infection in the CNS, including entry receptors and cytokines involved in neuroinflammatory conditions. Moreover, it explains several neurodegenerative disorders associated with COVID-19. Finally, we suggest inflammasome and JaK inhibitors as potential therapeutic strategies for neurodegenerative diseases.
Comparison of cardiovascular magnetic resonance characteristics and clinical prognosis in left ventricular noncompaction patients with and without arrhythmia
Authors: Zhou Zi-qi , He Wen-chong , Li Xiao , Bai Wei , Huang Wei , Hou Rui-lai , Wang Yi-ning , Guo Ying-kun 
Published: February 2022

Abstract
Background
Left ventricular noncompaction (LVNC) is a rare type of cardiomyopathy, and one of its clinical manifestations is arrhythmia. Cardiovascular magnetic resonance (CMR) is valuable for the diagnosis and prognosis of LVNC. However, studies are lacking on the use of CMR for LVNC patients with arrhythmia. This study aimed to characterize and compare CMR features and prognosis in LVNC patients with and without arrhythmia.

Methods
Eighty-four LVNC patients diagnosed by CMR were enrolled retrospectively in this study. Clinical data, arrhythmia characteristics, and CMR parameters were collected. Patients were divided into different groups according to the arrhythmia characteristics and CMR manifestations for statistical analysis and comparison. Ventricular tachycardia (VT), ventricular fibrillation (Vf), ventricular flutter (VFL), III° atrioventricular block (III° AVB), Wolff–Parkinson–White syndrome (WPW) and ventricular escape (VE) were defined as malignant arrhythmias and benign arrhythmias included premature ventricular contraction, atrial premature beats, atrial fibrillation, supraventricular tachycardia, supraventricular premature beat, bundle branch block, atrial flutter and sinus tachycardia. The outcome events were defined as a composition event of cardiac death, rehospitalization for heart failure, heart transplantation, and implantation of an implantable cardioverter defibrillator (ICD).

Results
Sixty-seven LVNC patients (79.76%) mainly presented with arrhythmia, including premature ventricular beat (33 patients [27.73%]), bundle branch block (14 patients [11.77%]), electrocardiogram waveform changes (18 patients [15.13%]), and ventricular tachycardia (11 patients [9.24%]). The cardiac function and structure parameters had no significant difference among the nonarrhythmia group, benign arrhythmia group, and malignant arrhythmia group. However, the presence of late gadolinium enhancement (LGE) was higher in the malignant arrhythmia group than in the other two groups (p = 0.023). At a mean follow-up of 46 months, cardiac events occurred in twenty-three patients (46.94%). Kaplan–Meier analysis showed that there was no statistically significant difference in prognosis among the nonarrhythmia, benign, and malignant arrhythmia groups, but the patients with arrhythmia and association with LGE + or left ventricular ejection fraction (LVEF) < 30% had a higher risk than patients with LGE- or LVEF > 30% (LGE +, HR = 4.035, 95% CI 1.475–11.035; LVEF < 30%, HR = 8.131, 95% CI 1.805–36.636; P < 0.05).

Conclusions
In LVNC patients, the types of arrhythmias are numerous and unrepresentative, and arrhythmia is not the prognostic factor. Arrhythmia combined with presence of LGE or LVEF < 30% is associated with poor prognosis in LVNC patients.
Cross-sectional household transmission study of Cryptosporidium shows that C. hominis infections are a key risk factor for spread
Authors: McKerr Caoimhe , Chalmers Rachel M. , Elwin Kristin , Ayres Heather , Vivancos Roberto , O’Brien Sarah J. , Christley Robert M. 
Published: February 2022

Abstract
Background
Infection with the Cryptosporidium parasite causes over 4000 cases of diagnosed illness (cryptosporidiosis) in England and Wales each year. The incidence of sporadic disease has not been sufficiently established, and how frequently this arises from contact with other infected people is not well documented. This project aimed to explore potential transmission in the home and attempt to identify asymptomatic infections, which might play a role in transmission. Risk factors and characteristics associated with spread of infection in the home were described including any differences between Cryptosporidium species.

Methods
The study identified cryptosporidiosis cases from North West England and Wales over a year and invited them and their household to take part. Each household was sent a study pack containing study information and a questionnaire, and stool sample kits to provide samples from consenting household members. Cryptosporidium-positive stool samples, identified by immunofluorescence microscopy, were characterised using molecular methods to help describe any patterns of transmission. Characteristics of households with and without additional cases were described, and compared using odds ratios (OR) and a multivariable logistic regression identified independent risk factors for household transmission. Data collection ran for one year, beginning in September 2018 with an initial pilot phase.

Results
We enrolled 128 index cases and their households. Additional illness occurred in over a quarter of homes, each reporting an average of two additional cases. The majority of these were undiagnosed and unreported to surveillance. This burden was even greater in households where the index case was infected with C. hominis versus C. parvum, or the index case was under five years old, with mums and siblings most at risk of secondary infection. Only having an index case of C. hominis was independently associated with transmission in the multivariable model (OR 4.46; p = 0.01).

Conclusions
Cryptosporidium was a considerable burden in the home. At-risk homes were those where the index was less than five years old and/or infected with C. hominis. Of particular risk were female caregivers and siblings. Hygiene advice should be specifically directed here.
This work provides evidence for humans as sources of C. hominis infection and that person-person is a key pathway. We recommend that all stools submitted for the investigation of gastrointestinal pathogens are tested for Cryptosporidium to better capture cases, inclusion of speciation data in routine surveillance, and the consideration of specific clinical advice on prevention for high-risk homes.
Novel heterozygous compound TRMT5 mutations associated with combined oxidative phosphorylation deficiency 26 in a Chinese family: a case report
Authors: Wu Shuiyan , Li Weixi , Bai Zhenjiang , Huang Saihu , Yang Daoping , Chen Hongmei , Li Ying , Liu Ying , Lv Haitao 
Published: February 2022

Abstract
Background
Combined oxidative phosphorylation deficiency 26 (COXPD26) is an autosomal recessive disorder characterized by early onset, developmental delay, gastrointestinal dysfunction, shortness of breath, exercise intolerance, hypotonia and muscle weakness, neuropathy, and spastic diplegia. This disease is considered to be caused by compound heterozygous mutations in the TRMT5 gene.

Case presentation
In this study, we report a female child with COXPD26 manifesting as shortness of breath, gastrointestinal dysmotility, severe developmental delay, muscle hypotonia and weakness, exercise intolerance, renal and hepatic defects, and recurrent seizures with spastic diplegia. Interestingly, the hepatic feature was first observed in a COXPD26 patient. Medical exome sequencing with high coverage depth was employed to identify potential genetic variants in the patient. Novel compound heterozygous mutations of the TRMT5 gene were detected, which were c.881A>C (p.E294A) from her mother and c.1218G>C (p.Q406H) and c.1481C>T (p.T494M) from her father.

Conclusion
The newly emerged clinical features and mutations of this patient provide useful information for further exploration of genotype–phenotype correlations in COXPD26.
A novel case of prolonged Ifosfamide encephalopathy and long-term treatment with methylene blue: a case report and review of literature
Authors: Chain Gabriel , Kalia Mudit , Kestenbaum Karen , Pappas Lara , Sechser-Perl Anna , Campino Gadi Abebe , Zaghloul Nibal 
Published: February 2022

Abstract
Background
Encephalopathy following Ifosfamide treatment is a well-described phenomenon that is typically treated with Methylene Blue (MB). Chloroacetaldehyde, a potentially neurotoxic metabolite of Ifosfamide is hypothesized to cause this encephalopathy. Current guidelines for treatment is to stop Ifosfamide and provide supportive care. MB acts to inhibit Chloroacetaldehyde formation and has been described as a therapy and prophylaxis for Ifosfamide-encephalopathy. MB is effective within 30 min and lasts up to 3 days. Prolonged encephalopathy and MB therapy has not been described in the literature as lasting longer than 30 days following treatment.

Case presentation
We present the case of an 11-year-old female with autistic spectrum disorder and recurrent episodes of severe somnolence for 7 months following Ifosfamide therapy for her Non-Germinomatous Germ Cell Tumor (GCT). Periods of somnolence occurred prior to receiving cranial RT. Administration of MB gave immediate but limited response, with resolution of somnolence lasting 1-2 days between administrations. The somnolence could not be explained by neuroimaging or laboratory evaluation, but EEG indicated persistent encephalopathy.

Conclusion
A literature review determines that neurotoxicity is a side effect of Ifosfamide, but this effect has not been described persisting longer than 30 days. Our case continued to require treatment with MB for 7 months following cessation of therapy. We report these novel clinical findings, and hypothesize that there could be a genetic/metabolic component linking this reaction to Ifosfamide with the case patient’s pre-existing autism. This possible association may also correlate to the already-established link between autism and the development of GCTs. This hypothesis leads to further discussion on the suitable usage of Ifosfamide in children with co-morbidities and the necessity of screening prior to its usage.
Estimation the medical cost of multiple sclerosis in Iran; 2019–2020
Authors: Asadollahi Mina , Darvishi Ali , Azimi Amirreza , Annabi Majid , Jafariazar Zahra , Heshmat Ramin 
Published: February 2022

Abstract
Background
Due to the high and increasing economic burden of chronic diseases, including Multiple sclerosis (MS), we aimed to investigate the medical cost of MS in Iran.

Methods
This is a descriptive cross-sectional study which conducted using comprehensive national prescription data from Iran’s Health Insurance Organization (IHIO) and rehabilitation data from Ministry of Health and Iran Welfare Organization. The time period considered for this study was 2019–2020. In order to calculate the medical cost of MS, the cost-of-illness (COI) method was used based on the prevalence-based approach and the cost of medications, determining and diagnosing the MS risk, follow-up and rehabilitation was estimated.

Results
The total medical cost of MS in Iran in 2019–2020 was estimated at $238,124,160, which medications and rehabilitation services had the largest share in the medical cost of MS in Iran with 80 and 19%, respectively, and the cost share of determining and diagnosing of the disease risk accounted for about less than 1%. The total medication cost was estimated to be equal to $192,298 thousand. The total cost of determining and diagnosing of the MS risk was estimated at $348,574 and the total cost of rehabilitation services for all MS subgroups in 2019–2020 was estimated at $45,477,205.

Conclusions
Results of calculating the medical cost of MS in Iran in 2019–2020 showed a significant burden on the Iranian health care system and society, among which the medication cost had the largest share, which requires serious attention of health system policymakers.
Systematic review of Mendelian randomization studies on risk of cancer
Authors: Markozannes Georgios , Kanellopoulou Afroditi , Dimopoulou Olympia , Kosmidis Dimitrios , Zhang Xiaomeng , Wang Lijuan , Theodoratou Evropi , Gill Dipender , Burgess Stephen , Tsilidis Konstantinos K. 
Published: February 2022

Abstract
Background
We aimed to map and describe the current state of Mendelian randomization (MR) literature on cancer risk and to identify associations supported by robust evidence.

Methods
We searched PubMed and Scopus up to 06/10/2020 for MR studies investigating the association of any genetically predicted risk factor with cancer risk. We categorized the reported associations based on a priori designed levels of evidence supporting a causal association into four categories, namely robust, probable, suggestive, and insufficient, based on the significance and concordance of the main MR analysis results and at least one of the MR-Egger, weighed median, MRPRESSO, and multivariable MR analyses. Associations not presenting any of the aforementioned sensitivity analyses were not graded.

Results
We included 190 publications reporting on 4667 MR analyses. Most analyses (3200; 68.6%) were not accompanied by any of the assessed sensitivity analyses. Of the 1467 evaluable analyses, 87 (5.9%) were supported by robust, 275 (18.7%) by probable, and 89 (6.1%) by suggestive evidence. The most prominent robust associations were observed for anthropometric indices with risk of breast, kidney, and endometrial cancers; circulating telomere length with risk of kidney, lung, osteosarcoma, skin, thyroid, and hematological cancers; sex steroid hormones and risk of breast and endometrial cancer; and lipids with risk of breast, endometrial, and ovarian cancer.

Conclusions
Despite the large amount of research on genetically predicted risk factors for cancer risk, limited associations are supported by robust evidence for causality. Most associations did not present a MR sensitivity analysis and were thus non-evaluable. Future research should focus on more thorough assessment of sensitivity MR analyses and on more transparent reporting.