bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular profile of FLT3-mutated relapsed/refractory patients with AML in the phase 3 ADMIRAL study of gilteritinib
Authors: Smith Catherine C. , Levis Mark J. , Perl Alexander E. , Hill Jason E. , Rosales Matt , Bahceci Erkut
Published: February 2022

The phase 3 Study of ASP2215 Versus Salvage Chemotherapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) With FMS-like Tyrosine Kinase (FLT3) Mutation (ADMIRAL) trial demonstrated the superiority of the FLT3 inhibitor, gilteritinib, to salvage chemotherapy (SC) in patients with FLT3-mutated relapsed or refractory (R/R) AML. Baseline comutations, FLT3-internal tandem duplication (ITD) allelic ratio and length, and treatment-emergent mutations were analyzed in patients in the ADMIRAL trial. Baseline comutations were grouped according to gene subgroups (DNA methylation/hydroxymethylation, transcription, chromatin–spliceosome, receptor tyrosine kinase-Ras signaling, TP53-aneuploidy, NPM1, DNMT3A, DNMT3A/NPM1, WT-1, and IDH1/IDH2). Across all but 1 gene subgroup (TP53-aneuploidy), higher pretransplant response rates and a trend toward longer overall survival were observed with gilteritinib vs SC. Patients with DNMT3A/NPM1 comutations who received gilteritinib had the most favorable outcomes of any molecular subgroup analyzed. Survival outcomes with gilteritinib were not adversely affected by FLT3-ITD allelic ratio, FLT3-ITD length, or multiple FLT3-ITD mutations. Among patients who relapsed on gilteritinib, Ras/mitogen-activated protein kinase (MAPK) pathway and FLT3 F691L gene mutations were the most common mutational events associated with treatment resistance. However, the occurrence of Ras/MAPK pathway gene mutations at baseline did not preclude a clinical benefit from gilteritinib. Acquisition of multiple Ras/MAPK pathway gene mutations at relapse suggests a high level of pathway reactivation is needed to overcome the gilteritinib treatment effect. These findings provide insight into the R/R AML molecular profile and the impact of FLT3 inhibitors on mutational evolution associated with treatment resistance and benefit of gilteritinib across a wide spectrum of molecular and genetic subgroups in FLT3-mutated R/R AML. This trial was registered at www.clinicaltrials.gov as #NCT02421939.
A prognostic model to predict survival after 6 months of ruxolitinib in patients with myelofibrosis
Authors: Maffioli Margherita , Mora Barbara , Ball Somedeb , Iurlo Alessandra , Elli Elena Maria , Finazzi Maria Chiara , Polverelli Nicola , Rumi Elisa , Caramella Marianna , Carraro Maria Cristina , D’Adda Mariella , Molteni Alfredo , Sissa Cinzia , Lunghi Francesca , Vismara Alessandro , Ubezio Marta , Guidetti Anna , Caberlon Sabrina , Anghilieri Michela , Komrokji Rami , Cattaneo Daniele , Della Porta Matteo Giovanni , Giorgino Toni , Bertù Lorenza , Brociner Marco , Kuykendall Andrew , Passamonti Francesco
Published: February 2022

Ruxolitinib (RUX) is extensively used in myelofibrosis (MF). Despite its early efficacy, most patients lose response over time and, after discontinuation, have a worse overall survival (OS). Currently, response criteria able to predict OS in RUX-treated patients are lacking, leading to uncertainty regarding the switch to second-line treatments. In this study, we investigated predictors of survival collected after 6 months of RUX in 209 MF patients participating in the real-world ambispective observational RUXOREL-MF study (NCT03959371). Multivariable analysis identified the following risk factors: (1) RUX dose <20 mg twice daily at baseline, months 3 and 6 (hazard ratio [HR], 1.79; 95% confidence interval [CI], 1.07-3.00; P = .03), (2) palpable spleen length reduction from baseline ≤30% at months 3 and 6 (HR, 2.26; 95% CI, 1.40-3.65; P = .0009), (3) red blood cell (RBC) transfusion need at months 3 and/or 6 (HR, 1.66; 95% CI, 0.95-2.88; P = .07), and (4) RBC transfusion need at all time points (ie, baseline and months 3 and 6; HR, 2.32; 95% CI, 1.19-4.54; P = .02). Hence, we developed a prognostic model, named Response to Ruxolitinib After 6 Months (RR6), dissecting 3 risk categories: low (median OS, not reached), intermediate (median OS, 61 months; 95% CI, 43-80), and high (median OS, 33 months; 95% CI, 21-50). The RR6 model was validated and confirmed in an external cohort comprised of 40 MF patients. In conclusion, the RR6 prognostic model allows for the early identification of RUX-treated MF patients with impaired survival who might benefit from a prompt treatment shift.
A data management infrastructure for the integration of imaging and omics data in life sciences
Authors: Kuhn Cuellar Luis , Friedrich Andreas , Gabernet Gisela , de la Garza Luis , Fillinger Sven , Seyboldt Adrian , Koch Tobias , zur Oven-Krockhaus Sven , Wanke Friederike , Richter Sandra , Thaiss Wolfgang M. , Horger Marius , Malek Nisar , Harter Klaus , Bitzer Michael , Nahnsen Sven
Published: February 2022

Background

As technical developments in omics and biomedical imaging increase the throughput of data generation in life sciences, the need for information systems capable of managing heterogeneous digital assets is increasing. In particular, systems supporting the findability, accessibility, interoperability, and reusability (FAIR) principles of scientific data management.

Results

We propose a Service Oriented Architecture approach for integrated management and analysis of multi-omics and biomedical imaging data. Our architecture introduces an image management system into a FAIR-supporting, web-based platform for omics data management. Interoperable metadata models and middleware components implement the required data management operations. The resulting architecture allows for FAIR management of omics and imaging data, facilitating metadata queries from software applications. The applicability of the proposed architecture is demonstrated using two technical proofs of concept and a use case, aimed at molecular plant biology and clinical liver cancer research, which integrate various imaging and omics modalities.

Conclusions

We describe a data management architecture for integrated, FAIR-supporting management of omics and biomedical imaging data, and exemplify its applicability for basic biology research and clinical studies. We anticipate that FAIR data management systems for multi-modal data repositories will play a pivotal role in data-driven research, including studies which leverage advanced machine learning methods, as the joint analysis of omics and imaging data, in conjunction with phenotypic metadata, becomes not only desirable but necessary to derive novel insights into biological processes.
Maternal microbiota-derived metabolic profile in fetal murine intestine, brain and placenta
Authors: Pessa-Morikawa Tiina , Husso Aleksi , Kärkkäinen Olli , Koistinen Ville , Hanhineva Kati , Iivanainen Antti , Niku Mikael
Published: February 2022

Background

The maternal microbiota affects the development of the offspring by microbial metabolites translocating to the fetus. To reveal the spectrum of these molecular mediators of the earliest host-microbe interactions, we compared placenta, fetal intestine and brain from germ-free (GF) and specific pathogen free (SPF) mouse dams by non-targeted metabolic profiling.

Results

One hundred one annotated metabolites and altogether 3680 molecular features were present in significantly different amounts in the placenta and/or fetal organs of GF and SPF mice. More than half of these were more abundant in the SPF organs, suggesting their microbial origin or a metabolic response of the host to the presence of microbes. The clearest separation was observed in the placenta, but most of the molecular features showed significantly different levels also in the fetal intestine and/or brain. Metabolites that were detected in lower amounts in the GF fetal organs included 5-aminovaleric acid betaine, trimethylamine N-oxide, catechol-O-sulphate, hippuric and pipecolic acid. Derivatives of the amino acid tryptophan, such as kynurenine, 3-indolepropionic acid and hydroxyindoleacetic acid, were also less abundant in the absence of microbiota. Ninety-nine molecular features were detected only in the SPF mice. We also observed several molecular features which were more abundant in the GF mice, possibly representing precursors of microbial metabolites or indicators of a metabolic response to the absence of microbiota.

Conclusions

The maternal microbiota has a profound impact on the fetal metabolome. Our observations suggest the existence of a multitude of yet unidentified microbially modified metabolites which pass through the placenta into the fetus and potentially influence fetal development.
Factors related to treatment adherence behaviors among old-age hemodialysis patients in Hamadan, Iran: the application of the extended theory of planned behavior during Covid-19 pandemic
Authors: Sheikh Vida , Barati Majid , Khazaei Salman , Jormand Hanieh
Published: February 2022

Purpose

This study aimed to identify the factors related to treatment adherence behaviors among old-age hemodialysis patients in Hamadan based on the Extended Theory of Planned Behavior (ETPB) during the covid-19 pandemic.

Methods

This cross-sectional study was conducted from January to March 2021 in Hamadan, Iran. 191 hemodialysis patients were recruited who were referred to hemodialysis centers via the census method. Data were collected by a questionnaire containing items on socio-demographic information, End-Stage Renal Disease Adherence (ESRD-Adherence) Questionnaire, and ETPB constructs scale. Data analysis was performed using descriptive statistics and structural equation modeling.

Results

The mean (SD) age of participants was 62.49 (10.66). Also, the mean (SD) hemodialysis vintage/Month of them was 36.56 (43.34). Moreover, Treatment Adherence Behaviors are associated with education level, sex, and marital status (p < 0.001). Besides, Perceive Behavior Control (β = 0.414, t-value = 3.810) associated with intention. Also, intention (β = 0.158, t-value = 1.976) was associated to adherence behaviors. No significant associations were observed between positive attitudes, subjective norms, a perceived threat with intention, and adherence behaviors. The model explained about 54% of the variance of adherence behaviors. Finally, the goodness of fit index of 0.78, indicating the model good fit.

Conclusion

The present study demonstrates that some of the ETPB constructs such as perceived behavior control and intention are useful to improve adherence among the oldest hemodialysis patients. Also. This framework is revealed alongside the theory of planned behavior (TPB) applicable in the treatment adherence of old-age hemodialysis patients.
Secular trends in incidence and mortality of cervical cancer in India and its states, 1990-2019: data from the Global Burden of Disease 2019 Study
Authors: Singh Mayank , Jha Ravi Prakash , Shri Neha , Bhattacharyya Krittika , Patel Priyanka , Dhamnetiya Deepak
Published: February 2022

Background

Cervical cancer is the fourth most common cancer that occurs to women worldwide. This study aims to assess trends in incidence and mortality of cervical cancer in India and its states over past three decades for tracking the progress of strategies for the prevention and control of cervical cancer.

Methods

Data on cervical cancer incidence and mortality from 1990 to 2019 for India and its states were extracted from Global Burden of Disease study and were utilized for the analysis. Spatial and rank map has been used to see the changes in incidence and mortality of cervical cancer in different Indian states. Further, joinpoint regression analysis is applied to determine the magnitude of the time trends in the age standardized incidence and mortality rates of cervical cancer. We obtained the average annual percent change (AAPC) and corresponding 95% confidence intervals (CI) for each state.

Results

Overall, from 1990 to 2019 Jharkhand (Incidence: -50.22%; Mortality: -56.16%) recorded the highest percentage decrement in cervical cancer incidence and mortality followed by the Himachal Pradesh (Incidence: -48.34%; Mortality: -53.37%). Tamilnadu (1st rank), Jammu & Kashmir and Ladakh (32nd rank) maintained the same rank over the period of three decade for age standardized cervical cancer incidence and mortality. The regression model showed a significant declining trend in India between 1990 and 2019 for age standardized incidence rate (AAPC: −0.82; 95%CI: −1.39 to −0.25; p < 0.05) with highest decline in the period 1998-2005 (AAPC: −3.22; 95%CI: −3.83 to −2.59; p < 0.05). Similarly, a significant declining trend was observed in the age standardized mortality rate of India between 1990 and 2019(AAPC: −1.35; 95%CI: −1.96 to −0.75; p < 0.05) with highest decline in the period 1998-2005 (AAPC: −3.52; 95%CI: −4.17 to −2.86; p < 0.05).

Conclusion

Though the incidence and mortality of cervical cancer declined over past three decades but it is still a major public health problem in India. Information, education and communication activities for girls, boys, parents and community for the prevention and control of cervical cancer should be provided throughout the country.
Neonatal mortality in a public referral hospital in southern Haiti: a retrospective cohort study
Authors: Dev Alka , Casseus Michelucia , Baptiste Wilhermine Jean , LeWinter Emma , Joseph Patrice , Wright Peter
Published: February 2022

Background

Haiti has the highest rate of neonatal mortality in the Latin America and Caribbean region. While the rate of facility births in Haiti has doubled over the past two decades, there have been no comparable reductions in maternal or neonatal mortality. Little data is available on the clinical characteristics of complications and morbidities among newborns requiring hospitalization after birth and their contribution to neonatal mortality. There is a need to better understand the status of newborn clinical care capacity in Haiti to prioritize training and resources.

Methods

We performed a retrospective observational cohort study of neonates admitted to a large public referral hospital in southern Haiti in the first 2 years of operation of a new neonatal unit that we established. All neonate cases hospitalized in the unit in these 2 years were reviewed and analyzed to identify their clinical characteristics and outcomes. Multivariable logistic regression was used to identify independent risk factors of hospital mortality. We present the outcomes for 1399 neonates admitted to the unit during August 2017 and August 2019.

Results

The leading cause of death was prematurity, followed by hypoxia and infection. Inborn neonates had better rates of hospital survival than those born elsewhere; they were also more likely to be born via cesarean section and to be admitted immediately following birth. There were no differences between the proportion of premature or low-birth-weight babies born at the hospital or elsewhere. Mortality in the second year of the unit’s operation was 12%, almost half that of the first year (21%). Multivariable regression analysis showed that mortality was consistently higher among premature and very low birthweight babies.

Conclusions

With modest investments, we were able to halve the mortality on a neonatal unit in Haiti. Resources are needed to address prematurity as an important outcome since hospital mortality was significant in this group. To this end, investment in uninterrupted supplies of oxygen and antibiotics, as well as ensuring adequate newborn resuscitation, infection control, laboratory testing, and timely morbidity and mortality reviews would go a long way toward lowering hospital mortality in Haiti.
Rising through the pandemic: a scoping review of quality improvement in public health during the COVID-19 pandemic
Authors: Yin X. Cindy , Pang Michelle , Law Madelyn P. , Guerra Fiona , O’Sullivan Tracey , Laxer Rachel E. , Schwartz Brian , Khan Yasmin
Published: February 2022

Background

The COVID-19 pandemic generated a growing interest in and need for evidence-based tools to facilitate the implementation of emergency management strategies within public health practice. Quality improvement (QI) is a key framework and philosophy to guide organizational emergency response efforts; however, the nature and extent to which it has been used in public health settings during the COVID-19 pandemic remains unclear.

Methods

We conducted a scoping review of literature published January 2020 – February 2021 and focused on the topic of QI at public health agencies during the COVID-19 pandemic. The search was conducted using four bibliographic databases, in addition to a supplementary grey literature search through custom Google search engines and targeted website search methods. Of the 1,878 peer-reviewed articles assessed, 15 records met the inclusion criteria. An additional 11 relevant records were identified during the grey literature search, for a total of 26 records included in the scoping review.

Results

Records were organized into five topics: 1) collaborative problem solving and analysis with stakeholders; 2) supporting learning and capacity building in QI; 3) learning from past emergencies; 4) implementing QI methods during COVID-19; and 5) evaluating performance using frameworks/indicators.

Conclusions

The literature indicates that QI-oriented activities are occurring at the organizational and program levels to enhance COVID-19 response. To optimize the benefits that QI approaches and methodologies may offer, it is important for public health agencies to focus on both widespread integration of QI as part of an organization’s management philosophy and culture, as well as project level activities at all stages of the emergency management cycle.
Final-year medical students’ self-assessment of facets of competence for beginning residents
Authors: Bußenius Lisa , Harendza Sigrid , van den Bussche Hendrik , Selch Susan
Published: February 2022

Background

Final-year undergraduate medical students often do not feel well prepared for their start of residency training. Self-assessment of competences is important so that medical trainees can take responsibility for their learning. In this study, we investigated how final-year medical students self-assessed their competences as they neared their transition to postgraduate training. The aim was to identify areas for improvement in undergraduate training.

Methods

In the academic year 2019/2020, a national online survey was sent to final-year undergraduate medical students via their respective medical schools. The survey included ten facets of competence (FOC) most relevant for beginning residents. The participants were asked to self-assess their competence for each FOC on a 5-point Likert scale (1: strongly disagree to 5: strongly agree). We established an order of self-assessed FOC performance by means and calculated paired t-tests. Gender differences were assessed with independent t-tests.

Results

A total of 1083 students from 35 medical schools completed the questionnaire. Mean age was 27.2 ± 3.1 years and 65.8% were female. Students rated their performance highest in the FOCs ‘Teamwork and collegiality’ and ‘Empathy and openness’ (97.1 and 95.0% ‘strongly agree’ or ‘agree’, respectively) and lowest in ‘Verbal communication with colleagues and supervisors’ and ‘Scientifically and empirically grounded method of working’ (22.8 and 40.2% ‘strongly disagree’, ‘disagree’, or ‘neither agree nor disagree’, respectively). Women rated their performance of ‘Teamwork and collegiality’, ‘Empathy and openness’, and ‘Knowing and maintaining own personal bounds and possibilities’ significantly higher than men did (Cohen’s d > .2), while men showed higher self-assessed performance in ‘Scientifically and empirically grounded method of working’ than women (Cohen’s d = .38). The FOCs ‘Responsibility’, ‘Knowing and maintaining own personal bounds and possibilities’, ‘Structure, work planning, and priorities’, ‘Coping with mistakes’, and ‘Scientifically and empirically grounded method of working’ revealed lower self-assessed performance than the order of FOC relevance established by physicians for beginning residents.

Conclusions

The differences between the level of students’ self-assessed FOC performance and physicians’ ranking of FOC relevance revealed areas for improvement in undergraduate medical education related to health system sciences. Final-year students might benefit from additional or better training in management skills, professionalism, and evidence-based medicine. Surveys of self-assessed competences may be useful to monitor competence development during undergraduate training.
Teaching critical appraisal to large classes of undergraduate medical students using team-based learning versus group discussions: a randomized controlled trial
Authors: Daou Dayane , Chakhtoura Marlene , El-Yazbi Ahmed , Mukherji Deborah , Sbaity Eman , Refaat Marwan M. , Nabulsi Mona
Published: February 2022

Background

Evidence on the effectiveness of team-based learning in teaching critical appraisal to large classes of preclinical medical students is scarce. This study investigated whether team-based learning is effective in teaching critical appraisal to large classes of preclinical medical students.

Methods

Between April 2018 and May 2019, 107 first-year medical students were randomly allocated to receive instruction in critical appraisal using team-based learning or traditional group discussions as teaching methods. The primary outcome was students’ performance on the Berlin Questionnaire administered at the end of second year.

Results

Students’ mean (SD) age was 22.0 (0.7) years. Baseline characteristics of the two groups were similar (allpvalues > 0.05). The mean (SD) Berlin scores of both groups were 80.4 (11.6) and 80.1 (12.1) for team-based learning and group discussions, respectively. Multivariate stepwise linear regression analysis revealed that the student’s academic achievement in medical school was the sole predictor of performance on the Berlin Questionnaire (ß= 1.079,p< 0.001), adjusting for gender, Medical College Admission Test score, student’s self-reported preferred teaching method, rank upon admission to medical school, score on the Epidemiology and Biostatistics course, and teaching method (team-based learning versus group discussions).

Conclusions

Team-based learning and group discussions were equally effective instructional strategies to teach critical appraisal to large classes of undergraduate medical students. Replication of our findings is needed in other educational settings.

Trial Registration

Current Controlled TrialsISRCTN15430424, retrospectively registered on December 30, 2021.
Occipital condyle width (OCW) is a highly accurate predictor of body mass in therian mammals
Authors: Engelman Russell K.
Published: February 2022

Background

Body mass estimation is of paramount importance for paleobiological studies, as body size influences numerous other biological parameters. In mammals, body mass has been traditionally estimated using regression equations based on measurements of the dentition or limb bones, but for many species teeth are unreliable estimators of body mass and postcranial elements are unknown. This issue is exemplified in several groups of extinct mammals that have disproportionately large heads relative to their body size and for which postcranial remains are rare. In these taxa, previous authors have noted that the occiput is unusually small relative to the skull, suggesting that occiput dimensions may be a more accurate predictor of body mass.

Results

The relationship between occipital condyle width (OCW) and body mass was tested using a large dataset (2127 specimens and 404 species) of mammals with associated in vivo body mass. OCW was found to be a strong predictor of body mass across therian mammals, with regression models of Mammalia as a whole producing error values (~ 31.1% error) comparable to within-order regression equations of other skeletal variables in previous studies. Some clades (e.g., monotremes, lagomorphs) exhibited specialized occiput morphology but followed the same allometric relationship as the majority of mammals. Compared to two traditional metrics of body mass estimation, skull length, and head-body length, OCW outperformed both in terms of model accuracy.

Conclusions

OCW-based regression models provide an alternative method of estimating body mass to traditional craniodental and postcranial metrics and are highly accurate despite the broad taxonomic scope of the dataset. Because OCW accurately predicts body mass in most therian mammals, it can be used to estimate body mass in taxa with no close living analogues without concerns of insufficient phylogenetic bracketing or extrapolating beyond the bounds of the data. This, in turn, provides a robust method for estimating body mass in groups for which body mass estimation has previously been problematic (e.g., “creodonts” and other extinct Paleogene mammals).
An evaluation of circulating activated TAFI in septic DIC: a case series and review of the literature
Authors: Totoki Takaaki , Ito Takashi , Kakuuchi Midori , Yashima Nozomi , Maruyama Ikuro , Kakihana Yasuyuki
Published: February 2022

Background

Administration of recombinant human soluble thrombomodulin (rTM) is often used in Japan to treat septic disseminated intravascular coagulation (DIC). Thrombin-activatable fibrinolysis inhibitor (TAFI) is a fibrinolysis inhibitor activated by the thrombin-thrombomodulin complex, however, it is unknown whether circulating activated TAFI is increased after rTM administration in patients with DIC. Furthermore, the relationship between TAFI activation and the prognosis of septic DIC is not defined yet.

Case presentation

We report a series of 8 patient’s TAFI activation with septic DIC treated by rTM. We sought to investigate the effect of rTM on TAFI activation and the association of plasma activated TAFI (TAFIa/ai) levels with the prognosis of septic DIC.

Using plasma samples from clinical studies conducted from May 2016–March 2017 on eight patients with septic DIC at Kagoshima University Hospital, we measured plasma levels of total TAFI, TAFIa/ai, thrombin-antithrombin complex (TAT), prothrombin fragment 1 + 2 (F1 + 2), soluble fibrin (SF), antithrombin (AT), protein C (PC), protein S (PS), and plasminogen activator inhibitor-1 (PAI-1) before and after intravenous rTM administration. Then, we evaluated the relationship of these marker levels to prognosis. The thrombin-rTM complex activated TAFI in vitro in plasma from a healthy volunteer. However, TAFIa/ai levels did not significantly increase over baseline in the septic DIC patients after intravenous rTM administration. Baseline TAFIa/ai levels in non-survivors were significantly higher than those in survivors.

Conclusions

Plasma TAFIa/ai did not increase with rTM administration. Elevated baseline TAFIa/ai concentration may be a negative prognostic indicator in septic DIC. Larger studies are needed to confirm the in vivo effect of rTM on TAFI activation.
Lowering blood cholesterol does not affect neuroinflammation in experimental autoimmune encephalomyelitis
Authors: Vigne Solenne , Duc Donovan , Peter Benjamin , Rebeaud Jessica , Yersin Yannick , Ruiz Florian , Bressoud Valentine , Collet Tinh-Hai , Pot Caroline
Published: February 2022

Background

Multiple sclerosis (MS) is a chronic disabling disease of the central nervous system (CNS) commonly affecting young adults. There is increasing evidence that environmental factors are important in the development and course of MS. The metabolic syndrome (MetS) which comprises dyslipidemia has been associated with a worse outcome in MS disease. Furthermore, the lipid-lowering drug class of statins has been proposed to improve MS disease course. However, cholesterol is also rate-limiting for myelin biogenesis and promotes remyelination in MS animal models. Thus, the impact of circulating blood cholesterol levels during the disease remains debated and controversial.

Methods

We assessed the role of circulating cholesterol on the murine model of MS, the experimental autoimmune encephalomyelitis (EAE) disease using two different approaches: (1) the mouse model of familial hypercholesterolemia induced by low-density lipoprotein receptor (LDLr) deficiency, and (2) the use of the monoclonal anti-PCSK9 neutralizing antibody alirocumab, which reduces LDLr degradation and consequently lowers blood levels of cholesterol.

Results

Elevated blood cholesterol levels induced by LDLr deficiency did not worsen clinical symptoms of mice during EAE. In addition, we observed that the anti-PCSK9 antibody alirocumab did not influence EAE disease course, nor modulate the immune response in EAE.

Conclusions

These findings suggest that blood cholesterol level has no direct role in neuro-inflammatory diseases and that the previously shown protective effects of statins in MS are not related to circulating cholesterol.
A comparative human rights analysis of laws and policies for adolescent contraception in Uganda and Kenya
Authors: Perehudoff Katrina , Kibira Denis , Wuyts Elke , Pericas Carles , Omwoha Joyce , van den Ham Hendrika A. , Mantel-Teeuwisse Aukje K. , Michielsen Kristien
Published: February 2022

Background

Improving access to adolescent contraception information and services is essential to reduce unplanned adolescent pregnancies and maternal mortality in Uganda and Kenya, and attain the SDGs on health and gender equality. This research studies to what degree national laws and policies for adolescent contraception in Uganda and Kenya are consistent with WHO standards and human rights law.

Methods

This is a comparative content analysis of law and policy documents in force between 2010 and 2018 governing adolescent (age 10–19 years) contraception. Between and within country differences were analysed using WHO’s guidelines “Ensuring human rights in the provision of contraceptive information and services”.

Results

Of the 93 laws and policies screened, 26 documents were included (13 policies in Uganda, 13 policies in Kenya). Ugandan policies include a median of 1 WHO recommendation for adolescent contraception per policy (range 0–4) that most frequently concerns contraception accessibility. Ugandan policies have 6/9 WHO recommendations (14/24 sub-recommendations) and miss entirely WHO’s recommendations for adolescent contraception availability, quality, and accountability. On the other hand, most Kenyan policies consistently address multiple WHO recommendations (median 2 recommendations/policy, range 0–6), most frequently for contraception availability and accessibility for adolescents. Kenyan policies cover 8/9 WHO recommendations (16/24 sub-recommendations) except for accountability.

Conclusions

The current policy landscapes for adolescent contraception in Uganda and Kenya include important references to human rights and evidence-based practice (in WHO’s recommendations); however, there is still room for improvement. Aligning national laws and policies with WHO’s recommendations on contraceptive information and services for adolescents may support interventions to improve health outcomes, provided these frameworks are effectively implemented.
Prevalence and phenotype of eating disorders in assisted reproduction: a systematic review
Authors: Le Floch Marine , Crohin Anaïs , Duverger Philippe , Picard Aline , Legendre Guillaume , Riquin Elise
Published: February 2022

Background

Eating disorders (EDs) are common conditions that mainly affect women of reproductive age and have a major impact on fertility. Our systematic review focuses on the prevalence of EDs in patients in the process of assisted reproductive technique (ART) and describes the phenotypes of EDs identified.

Methods

Our systematic review is based on the PRISMA criteria. Articles were collected using the Medline/Pubmed, Web Of Science and Cochrane databases. The articles chosen had to mention the prevalence of ED in infertile patients undergoing ART and be cohort or case–control studies assessing the prevalence of ED during fertility treatment.

Main findings

Fifteen articles were included in this review. The prevalence of active ED varied between 0.13 and 44% depending on the types considered in each study. The main phenotypes described were EDNOS (eating disorder not otherwise specified) and binge eating disorders (BED) occurring in women with a normal body mass index (BMI) and a history of ED. Mainly subthreshold forms with cognitive distortions were described.

Conclusion

This review highlights a 6 times higher prevalence of EDs in infertile patients undergoing fertility treatment compared to regular pregnant women. However, diagnosing these conditions is complex. As a result, it is essential that professionals in contact with this population are alert to symptoms consistent with these conditions in order to refer them to specialized psychiatric care.
Networks to strengthen community social capital for suicide prevention in regional Australia: the LifeSpan suicide prevention initiative
Authors: Long Janet C. , Ruane Colum , Ellis Louise A. , Lake Rebecca , Le Roux Anneke , Testa Luke , Shand Fiona , Torok Michelle , Zurynski Yvonne
Published: February 2022

Introduction

Mental health services are fragmented in Australia leading to a priority being placed on whole-of-community approaches and integration. We describe the LifeSpan suicide prevention intervention developed by the Black Dog Institute that draws upon nine evidence-based community-wide strategies. We examined the suicide prevention Collaborative group at each site. We evaluated how the social capital of the community and service providers changed, and how the brokerage roles of the Collaborative affected integration of effort.

Methods

This was a two phase, explanatory mixed methods study. Participants were LifeSpan Coordinators, The Collaborative and working group members at four LifeSpan sites in New South Wales (three metropolitan/regional, one regional/rural). Quantitative social network data was collected through an online survey and analysed using Gephi software. Qualitative data through focus groups and interviews with Lifespan Coordinators and community stakeholders.

Results

The social network survey was administered in three sites and was completed by 83 people. Data gave quantitative evidence of increased engagement across key stakeholders in each region who had not previously been working together. Nominations of other collaborators showed this network extended beyond the formal structures of The Collaborative. LifeSpan Coordinators were empirically identified as key players in the networks. Qualitative data was collected from 53 individuals (18 interviews and five focus groups) from across all sites. Participants identified benefits of this collaborative approach including greater capacity to run activities, better communication between groups, identification of “who’s who” locally, improvement in the integration of priorities, services and activities, and personal support for previously isolated members. LifeSpan Coordinators were key to the smooth running of The Collaborative. This may represent a risk to sustainability if they left. The collaboration model that suited metropolitan sites was difficult to sustain in rural sites, but gains were seen in better coordinated postvention efforts.

Conclusion

LifeSpan Coordinators were noted to be exceptional people who magnified the benefits of collaboration. Geographic proximity was a potent driver of social capital. Initial engagement with local stakeholders was seen as essential but time-consuming work in the implementation phase. Coordinators reported this important work was not always acknowledged as part of their formal role.
The relationship between sleep quality and physical activity among patients with heart failure: a cross-sectional study
Authors: Esnaasharieh Fatemeh , Dehghan Mahlagha , Mangolian Shahrbabaki Parvin
Published: February 2022

Background

Sleep disorders are one of the most common and annoying problems among patients with heart failure, which decrease their quality of life. Participation in physical activity is one of the most effective methods to reduce sleep disorders; however, few patients participate. This study was conducted to examine the relationship between physical activities and sleep quality among heart failure patients.

Methods

A convenience sample of 100 patients with heart failure referred to rehabilitation centers in southeastern Iran was used in this descriptive cross-sectional study. The Pittsburgh Sleep Quality Index and the Rapid Assessment of Physical Activity (RAPA) were used to collect data. The Spearman correlation coefficient and regression were used to analyze the data. The significance level was < 0.05.

Results

The results revealed that the mean score of sleep quality was 8.74 ± 2.83, with the majority of them (84.47%) having poor sleep quality. The mean score of physical activity was 2.59 ± 1.33, and the majority of them (95.15%) had sub-optimal physical activity. There was a significant and inverse relationship between the total scores of sleep quality and physical activity, and patients’ sleep quality improved while physical activity increased. Physical activity, sex, history of heart surgery, and the stage of illness were found to account for 31% of the variances in patients’ sleep quality.

Conclusion

The results of this study showed better sleep quality among patients who were more physically active. Given that the majority of patients with heart failure suffer from sleep disorders, patients’ knowledge of physical activity should be increased to improve their quality of sleep and quality of life.
The applications of DNA methylation as a biomarker in kidney transplantation: a systematic review
Authors: Cristoferi Iacopo , Giacon Tommaso Antonio , Boer Karin , van Baardwijk Myrthe , Neri Flavia , Campisi Manuela , Kimenai Hendrikus J. A. N. , Clahsen - van Groningen Marian C. , Pavanello Sofia , Furian Lucrezia , Minnee Robert C.
Published: February 2022

Background

Although kidney transplantation improves patient survival and quality of life, long-term results are hampered by both immune- and non-immune-mediated complications. Current biomarkers of post-transplant complications, such as allograft rejection, chronic renal allograft dysfunction, and cutaneous squamous cell carcinoma, have a suboptimal predictive value. DNA methylation is an epigenetic modification that directly affects gene expression and plays an important role in processes such as ischemia/reperfusion injury, fibrosis, and alloreactive immune response. Novel techniques can quickly assess the DNA methylation status of multiple loci in different cell types, allowing a deep and interesting study of cells’ activity and function. Therefore, DNA methylation has the potential to become an important biomarker for prediction and monitoring in kidney transplantation.

Purpose of the study

The aim of this study was to evaluate the role of DNA methylation as a potential biomarker of graft survival and complications development in kidney transplantation.

Material and Methods

A systematic review of several databases has been conducted. The Newcastle–Ottawa scale and the Jadad scale have been used to assess the risk of bias for observational and randomized studies, respectively.

Results

Twenty articles reporting on DNA methylation as a biomarker for kidney transplantation were included, all using DNA methylation for prediction and monitoring. DNA methylation pattern alterations in cells isolated from different tissues, such as kidney biopsies, urine, and blood, have been associated with ischemia–reperfusion injury and chronic renal allograft dysfunction. These alterations occurred in different and specific loci. DNA methylation status has also proved to be important for immune response modulation, having a crucial role in regulatory T cell definition and activity. Research also focused on a better understanding of the role of this epigenetic modification assessment for regulatory T cells isolation and expansion for future tolerance induction-oriented therapies.

Conclusions

Studies included in this review are heterogeneous in study design, biological samples, and outcome. More coordinated investigations are needed to affirm DNA methylation as a clinically relevant biomarker important for prevention, monitoring, and intervention.
Iatrogenic ischiofemoral impingement due to high tibial osteotomy with overvalgization: a case report
Authors: Konrads Christian , Ahmad Sufian S. , Histing Tina , Ibrahim Maher
Published: February 2022

Background

Open wedge high tibial osteotomy is a standard procedure for frontal realignment. It is indicated in varus knee with reduced mechanical medial proximal tibia angle. Overcorrection producing a mechanical medial proximal tibia angle out of the normal range (85–90°) is not recommended because this would lead to unphysiological joint-line orientation. Osteotomies around the knee also influence the adjacent ankle and hip joints. For the hip, it is known that frontal alignment of the leg influences the ischiofemoral space. A decreased ischiofemoral space can lead to painful impingement between the ischial bone and the lesser trochanter.

Case presentation

A 53-year-old German woman presented with severe ischiofemoral impingement symptoms and valgus malalignment of the left leg after open wedge high tibial osteotomy, which was indicated and performed by an orthopedic surgeon with intention to treat medial knee pain due to degenerative arthritis of the medial compartment years after medial meniscectomy. The mechanical medial proximal tibia angle was 100.5°. We performed closed wedge high tibial osteotomy producing a mechanical medial proximal tibia angle of 90.0° and normal joint-line orientation. The hip pain was gone immediately after the surgery, and the patient had no signs of ischiofemoral impingement or hip pain at last follow-up 12 months after closed wedge high tibial osteotomy.

Conclusions

Frontal realignment osteotomy around the knee can create problems at adjacent joints. Overvalgization of the proximal tibia made the patient compensate by hyperadduction of the hip to enable full foot sole contact with the floor. Hyperadduction of the hip decreased the ischiofemoral space, leading to severe impingement. Therefore, meticulous planning of osteotomies is important not to produce unphysiological situations or unwanted negative effects at the level of an adjacent joint.
Sequential transplantation of exosomes and mesenchymal stem cells pretreated with a combination of hypoxia and Tongxinluo efficiently facilitates cardiac repair
Authors: Xiong Yuyan , Tang Ruijie , Xu Junyan , Jiang Wenyang , Gong Zhaoting , Zhang Lili , Li Xiaosong , Ning Yu , Huang Peisen , Xu Jun , Chen Guihao , Jin Chen , Li Xiangdong , Qian Haiyan , Yang Yuejin
Published: February 2022

Background

Bone marrow-derived mesenchymal stem cells (MSCs), which possess immunomodulatory characteristic, are promising candidates for the treatment of acute myocardial infarction (AMI). However, the low retention and survival rate of MSCs in the ischemic heart limit their therapeutic efficacy. Strategies either modifying MSCs or alleviating the inflammatory environment, which facilitates the recruitment and survival of the engrafted MSCs, may solve the problem. Thus, we aimed to explore the therapeutic efficacy of sequential transplantation of exosomes and combinatorial pretreated MSCs in the treatment of AMI.

Methods

Exosomes derived from MSCs were delivered to infarcted hearts through intramyocardial injection followed by the intravenous infusion of differentially pretreated MSCs on Day 3 post-AMI. Enzyme linked immunosorbent assay (ELISA) was performed to evaluate the inflammation level as well as the SDF-1 levels in the infarcted border zone of the heart. Echocardiography and histological analysis were performed to assess cardiac function, infarct size, collagen area and angiogenesis.

Results

Sequential transplantation of exosomes and the combinatorial pretreated MSCs significantly facilitated cardiac repair compared to AMI rats treated with exosomes alone. Notably, compared to the other three methods of cotransplantation, combinatorial pretreatment with hypoxia and Tongxinluo (TXL) markedly enhanced the CXCR4 level of MSCs and promoted recruitment, which resulted in better cardiac function, smaller infarct size and enhanced angiogenesis. We further demonstrated that exosomes effectively reduced apoptosis in MSCs in vitro.

Conclusion

Sequential delivery of exosomes and pretreated MSCs facilitated cardiac repair post-AMI, and combined pretreatment with hypoxia and TXL better enhanced the cardioprotective effects. This method provides new insight into the clinical translation of stem cell-based therapy for AMI.
Abnormal respiratory progenitors in fibrotic lung injury
Authors: Xie Ting , Lynn Heather , Parks William C. , Stripp Barry , Chen Peter , Jiang Dianhua , Noble Paul W.
Published: February 2022

Recent advances in single-cell RNA sequencing (scRNA-seq) and epithelium lineage labeling have yielded identification of multiple abnormal epithelial progenitor populations during alveolar type 2 (ATII) cell differentiation into alveolar type 1 (ATI) cells during regenerative lung post-fibrotic injury. These abnormal cells include basaloid/basal-like cells, ATII transition cells, and persistent epithelial progenitors (PEPs). These cells occurred and accumulated during the regeneration of distal airway and alveoli in response to both chronic and acute pulmonary injury. Among the alveolar epithelial progenitors, PEPs express a distinct Krt8+ phenotype that is rarely found in intact alveoli. However, post-injury, the Krt8+ phenotype is seen in dysplastic epithelial cells. Fully understanding the characteristics and functions of these newly found, injury-induced abnormal behavioral epithelial progenitors and the signaling pathways regulating their phenotype could potentially point the way to unique therapeutic targets for fibrosing lung diseases. This review summarizes recent advances in understanding these epithelial progenitors as they relate to uncovering regenerative mechanisms.