bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rare diseases in Tanzania: a National Call for Action to address policy and urgent needs of individuals with rare diseases
Authors: Kaywanga Frida , Alimohamed Mohamed Zahir , David Aneth Bella , Maeda Daniel , Mbarak Sharifa , Mavura Togolani , Nkya Siana , Ishengoma Deus S. 
Published: September 2022

AbstractA rare disease is generally defined as a condition which affects about 1 among 2000 people and currently, there are approximately 5000–8000 rare diseases (RDs) affecting over 400 million people world-wide. Although RDs may arise from different causes such as infections and environmental factors, about 80% are caused by genetic abnormalities. In Tanzania, there are no reports of the types of RDs, their incidence, distribution and numbers of individuals affected. In addition, there have been no strategies to map RDs in the country and develop a definition that fits the local context. Public awareness and understanding of RDs are very limited, and these lead to poor management and stigmatisation of patients. To address the ongoing problems, Tanzania joined other countries world-wide and global partners to commemorate the rare diseases day (RDD) for the first time in 2016 and subsequently every year. Unlike previous years where the RDD was organised by Ali Kimara Rare Diseases Foundation (AKRDF) with few partners, in 2020, a bigger event was co-hosted by Ali AKRDF and Tanzania Human Genetics Organization together with government representatives and other multiple partners. The organisers, government representatives and participants proposed a national “Call for Action” with the overall goal of improving the lives of patients/individuals with RDs. The call focuses and aims to address 17 strategic issues that are broadly categorised into four areas. These include generating demographic data of individuals with RDs; advocating for policies and guidelines for diagnosis, care, treatment and health financing; developing policies supporting public education, awareness and advocacy; and strengthening research, innovation and public–private partnerships. If adopted and implemented, the potential impacts of these recommendations will include improved access to adequate and high-quality health and education services, and policies and guidelines to address the current and future challenges facing individuals with RDs and their families.
Protein profiling of testicular tissue from boars with different levels of hyperactive sperm motility
Authors: van Son Maren , Våge Dag Inge , Skaugen Morten , Tremoen Nina Hårdnes , Gaustad Ann Helen , Zeremichael Teklu Tewoldebrhan , Myromslien Frøydis Deinboll , Grindflek Eli 
Published: September 2022

AbstractHyperactive sperm motility is important for successful fertilization. In the present study, a proteome profiling approach was performed to identify the differences between Landrace boars with different levels of hyperactive sperm motility in liquid extended semen. Two contrasts were studied: (i) high versus low levels of sperm hyperactivity at semen collection day and (ii) high versus low change in levels of sperm hyperactivity after 96 h semen storage. Testicular samples were analyzed on a Q Exactive mass spectrometer and more than 6000 proteins were identified in the 13 samples. The most significant differentially expressed proteins were mediator complex subunit 28 (MED28), cell division cycle 37 like 1 (CDC37L1), ubiquitin specific peptidase 10 (USP10), zinc finger FYVE-type containing 26 (ZFYVE26), protein kinase C delta (PRKCD), actinin alpha 4 (ACTN4), N(alpha)-acetyltransferase 30 (NAA30), C1q domain-containing (LOC110258309) and uncharacterized LOC100512926. Of the differentially expressed proteins, 11 have previously been identified as differentially expressed at the corresponding mRNA transcript level using the same samples and contrasts. These include sphingosine kinase 1 isoform 2 (SPHK1), serine and arginine rich splicing factor 1 (SRSF1), and tubulin gamma-1 (TUBG1) which are involved in the acrosome reaction and sperm motility. A mass spectrometry approach was applied to investigate the protein profiles of boars with different levels of hyperactive sperm motility. This study identified several proteins previously shown to be involved in sperm motility and quality, but also proteins with no known function for sperm motility. Candidates that are differentially expressed on both mRNA and protein levels are especially relevant as biological markers of semen quality.
Impact of IDH1 and IDH2 mutational subgroups in AML patients after allogeneic stem cell transplantation
Authors: Kunadt Desiree , Stasik Sebastian , Metzeler Klaus H. , Röllig Christoph , Schliemann Christoph , Greif Philipp A. , Spiekermann Karsten , Rothenberg-Thurley Maja , Krug Utz , Braess Jan , Krämer Alwin , Hochhaus Andreas , Scholl Sebastian , Hilgendorf Inken , Brümmendorf Tim H. , Jost Edgar , Steffen Björn , Bug Gesine , Einsele Hermann , Görlich Dennis , Sauerland Cristina , Schäfer-Eckart Kerstin , Krause Stefan W. , Hänel Mathias , Hanoun Maher , Kaufmann Martin , Wörmann Bernhard , Kramer Michael , Sockel Katja , Egger-Heidrich Katharina , Herold Tobias , Ehninger Gerhard , Burchert Andreas , Platzbecker Uwe , Berdel Wolfgang E. , Müller-Tidow Carsten , Hiddemann Wolfgang , Serve Hubert , Stelljes Matthias , Baldus Claudia D. , Neubauer Andreas , Schetelig Johannes , Thiede Christian , Bornhäuser Martin , Middeke Jan M. , Stölzel Friedrich ,   the A. M. L. Cooperative Group (AMLCG), Study Alliance Leukemia (SAL)
Published: September 2022

AbstractBackgroundThe role of allogeneic hematopoietic cell transplantation (alloHCT) in acute myeloid leukemia (AML) with mutatedIDH1/2has not been defined. Therefore, we analyzed a large cohort of 3234 AML patients in first complete remission (CR1) undergoing alloHCT or conventional chemo-consolidation and investigated outcome in respect toIDH1/2mutational subgroups (IDH1R132C, R132H and IDH2 R140Q, R172K).MethodsGenomic DNA was extracted from bone marrow or peripheral blood samples at diagnosis and analyzed forIDHmutations with denaturing high-performance liquid chromatography, Sanger sequencing and targeted myeloid panel next-generation sequencing, respectively. Statistical as-treated analyses were performed using R and standard statistical methods (Kruskal–Wallis test for continuous variables, Chi-square test for categorical variables, Cox regression for univariate and multivariable models), incorporating alloHCT as a time-dependent covariate.ResultsAmong 3234 patients achieving CR1, 7.8% harboredIDH1mutations (36% R132C and 47% R132H) and 10.9% carriedIDH2mutations (77% R140Q and 19% R172K). 852 patients underwent alloHCT in CR1. Within the alloHCT group, 6.2% had anIDH1mutation (43.4% R132C and 41.4% R132H) and 10% were characterized by anIDH2mutation (71.8% R140Q and 24.7% R172K). Variants IDH1 R132C and IDH2 R172K showed a significant benefit from alloHCT for OS (p = .017 andp = .049) and RFS (HR = 0.42,p = .048 andp = .009) compared with chemotherapy only. AlloHCT in IDH2 R140Q mutated AML resulted in longer RFS (HR = 0.4,p = .002).ConclusionIn this large as-treated analysis, we showed that alloHCT is able to overcome the negative prognostic impact of certainIDHmutational subclasses in first-line consolidation treatment and could pending prognostic validation, provide prognostic value for AML risk stratification and therapeutic decision making.
Epstein-Barr virus-associated acute pancreatitis: a clinical report and review of literature
Authors: Accomando Salvatore , Restivo Giulia Angela , Scalzo Simona , Guardino Melania , Corsello Giovanni , Giuffrè Mario 
Published: September 2022

Abstract
Background
Acute pancreatitis is a disorder of reversible inflammation of the pancreas. Only a few cases are related to infections and the most common pathogens are the viruses responsible for mumps, parotitis, and influenza. Epstein-Barr virus (EBV)-associated acute pancreatitis is a rare condition and it may occur in children and adults.

Case presentation
A 3-year-old female was admitted to the “G. Di Cristina” Children's Hospital in Palermo for vomiting and abdominal pain. Laboratory investigations revealed elevated amylase and lipase, with normal liver function tests. Abdominal ultrasound demonstrated an enlarged pancreas, with hypoechogenic areas; no biliary lithiasis was observed. Infectious disease serology was positive for the presence of EBV VCA IgM and IgG. A diagnosis of EBV-associated acute pancreatitis was made. The patient was treated conservatively and recovered.

Conclusions
Acute pancreatitis is rarely associated with EBV infection; a review of the English literature revealed only 10 pediatric and 6 adult cases. Patients with pancreatitis should always be evaluated for EBV serology, even in the absence of the typical clinical and hematological features of infectious mononucleosis. For these patients, good prognosis is generally expected.
The year 2021 in COVID-19 pandemic in children
Authors: Bozzola Elena , Caffarelli Carlo , Santamaria Francesca , Corsello Giovanni 
Published: September 2022

AbstractIn this article, the developments in the field of COVID-19 pandemic published in the Italian Journal of Pediatrics in 2021 are reflected. We describe progresses in SARS-CoV-2 transmission route, clinical presentation, diagnosis, treatment, and access to health care facilities in children. They led to substantial changes in the clinical approach.
Building Emotional Awareness and Mental Health (BEAM): study protocol for a phase III randomized controlled trial of the BEAM app-based program for mothers of children 18–36 months
Authors: Xie E. Bailin , Simpson Kaeley M. , Reynolds Kristin A. , Giuliano Ryan J. , Protudjer Jennifer L. P. , Soderstrom Melanie , Sauer-Zavala Shannon , Giesbrecht Gerald F. , Lebel Catherine , Mackinnon Anna L. , Rioux Charlie , Penner-Goeke Lara , Freeman Makayla , Salisbury Marlee R. , Tomfohr-Madsen Lianne , Roos Leslie E. 
Published: September 2022

AbstractBackgroundThe prevalence of maternal depression and anxiety has increased during the COVID-19 pandemic, and pregnant individuals are experiencing concerningly elevated levels of mental health symptoms worldwide. Many individuals may now be at heightened risk of postpartum mental health disorders. There are significant concerns that a cohort of children may be at-risk for impaired self-regulation and mental illness due to elevated exposure to perinatal mental illness. With both an increased prevalence of depression and limited availability of services due to the pandemic, there is an urgent need for accessible eHealth interventions for mothers of young children. The aims of this trial are to evaluate the efficacy of the Building Emotion Awareness and Mental Health (BEAM) app-based program for reducing maternal depression symptoms (primary outcome) and improve anxiety symptoms, parenting stress, family relationships, and mother and child functioning (secondary outcomes) compared to treatment as usual (TAU).MethodsA two-arm randomized controlled trial (RCT) with repeated measures will be used to evaluate the efficacy of the BEAM intervention compared to TAU among a sample of 140 mothers with children aged 18 to 36 months, who self-report moderate-to-severe symptoms of depression and/or anxiety. Individuals will be recruited online, and those randomized to the treatment group will participate in 10 weeks of psychoeducation modules, an online social support forum, and weekly group teletherapy sessions. Assessments will occur at 18–36 months postpartum (pre-test, T1), immediately after the last week of the BEAM intervention (post-test, T2), and at 3 months after the intervention (follow-up, T3).DiscussioneHealth interventions have the potential to address elevated maternal mental health symptoms, parenting stress, and child functioning concerns during and after the COVID-19 pandemic and to provide accessible programming to mothers who are in need of support. This RCT will build on an open pilot trial of the BEAM program and provide further evaluation of this evidence-based intervention. Findings will increase our understanding of depression in mothers with young children and reveal the potential for long-term improvements in maternal and child health and family well-being.Trial registrationClinicalTrials.govNCT05306626. Registered on April 1, 2022
Protocol for the development of a core domain set for individuals with ankle osteoarthritis
Authors: Alanazi Sultan Ayyadah , Vicenzino Bill , van Bergen Christiaan J. A. , Hunter David J. , Wikstrom Erik A. , Menz Hylton B. , Golightly Yvonne M. , Smith Michelle D. 
Published: September 2022

Abstract
Background
Ankle osteoarthritis (OA) is a debilitating health condition that is increasing in prevalence. Currently, there are no evidence-based guidelines for managing ankle OA. One of the current challenges to establishing guidelines is the lack of a widely agreed-upon set of outcome measures that are consistently used in ankle OA research. Without a set of agreed-upon outcome measures, it is difficult to synthesise clinical trial outcomes through meta-analysis—an essential element of evidence-informed practice. In order to develop an appropriate set of outcome measures for ankle OA, it is important first to develop a core domain set. In this protocol, we describe the methodological approach that we will use to develop such a core domain set for ankle OA.

Methods
We established an international steering committee to guide the development of a core domain set for ankle OA. The core domain set development will follow a multi-staged approach consisting of three phases, involving participation by patients and clinicians/healthcare professionals. In phase 1, a list of candidate domains will be gleaned from (a) a scoping review of outcome measures used in ankle OA research, (b) qualitative interviews with individuals with ankle OA, and (c) qualitative interviews with healthcare professionals with expertise in ankle OA. In phase 2, the steering committee will review and generate a list of candidate domains from those gleaned in phase 1. In phase 3, this list of candidate domains will be considered in a Delphi process to reach a consensus on a core domain set. We anticipated this will involve 3 rounds of surveys.

Conclusion
This protocol describes the methods that will be used to develop a core domain set of health-related aspects for ankle OA. Importantly, it will include both healthcare professional and patient involvement. This is a prerequisite step to developing a core outcome set for ankle OA that should be reported in all clinical trials for ankle OA. The findings will be widely disseminated across peer-refereed publication(s) and national and international conferences, as well as via relevant professional societies, patient support group organisations, and social media platforms.

Project registration
This project is registered with the Core Outcome Measures in Effectiveness Trials (COMET) database on 17 March 2021. https://www.comet-initiative.org/Studies/Details/1837.
Hamstrings force-length relationships and their implications for angle-specific joint torques: a narrative review
Authors: Kellis Eleftherios , Blazevich Anthony J. 
Published: September 2022

AbstractTemporal biomechanical and physiological responses to physical activity vary between individual hamstrings components as well as between exercises, suggesting that hamstring muscles operate differently, and over different lengths, between tasks. Nevertheless, the force-length properties of these muscles have not been thoroughly investigated. The present review examines the factors influencing the hamstrings’ force-length properties and relates them to in vivo function. A search in four databases was performed for studies that examined relations between muscle length and force, torque, activation, or moment arm of hamstring muscles. Evidence was collated in relation to force-length relationships at a sarcomere/fiber level and then moment arm-length, activation-length, and torque-joint angle relations. Five forward simulation models were also used to predict force-length and torque-length relations of hamstring muscles. The results show that, due to architectural differences alone, semitendinosus (ST) produces less peak force and has a flatter active (contractile) fiber force-length relation than both biceps femoris long head (BFlh) and semimembranosus (SM), however BFlh and SM contribute greater forces through much of the hip and knee joint ranges of motion. The hamstrings’ maximum moment arms are greater at the hip than knee, so the muscles tend to act more as force producers at the hip but generate greater joint rotation and angular velocity at the knee for a given muscle shortening length and speed. However, SM moment arm is longer than SM and BFlh, partially alleviating its reduced force capacity but also reducing its otherwise substantial excursion potential. The current evidence, bound by the limitations of electromyography techniques, suggests that joint angle-dependent activation variations have minimal impact on force-length or torque-angle relations. During daily activities such as walking or sitting down, the hamstrings appear to operate on the ascending limbs of their force-length relations while knee flexion exercises performed with hip angles 45–90° promote more optimal force generation. Exercises requiring hip flexion at 45–120° and knee extension 45–0° (e.g. sprint running) may therefore evoke greater muscle forces and, speculatively, provide a more optimum adaptive stimulus. Finally, increases in resistance to stretch during hip flexion beyond 45° result mainly from SM and BFlh muscles.
Chicken cathelicidin-2 promotes NLRP3 inflammasome activation in macrophages
Authors: Peng Lianci , Tian Hongliang , Lu Yi , Jia Kaixiang , Ran Jinrong , Tao Qi , Li Gang , Wan Chao , Ye Chao , Veldhuizen Edwin J. A. , Chen Hongwei , Fang Rendong 
Published: September 2022

AbstractChicken cathelicidin-2 (CATH-2) as a host defense peptide has been identified to have potent antimicrobial and immunomodulatory activities. Here, we reported the mechanism by which CATH-2 modulates NLRP3 inflammasome activation. Our results show that CATH-2 and ATP as a positive control induced secretion of IL-1β and IL-1α in LPS-primed macrophages but did not affect secretion of IL-6, IL-12 and TNF-α. Furthermore, CATH-2 induced caspase-1 activation and oligomerization of apoptosis-associated speck-like protein containing a carboxy- terminal caspase recruitment domain (ASC), which is essential for NLRP3 inflammasome activation. However, CATH-2 failed to induce IL-1β secretion in Nlrp3−/−, Asc−/− and Casp1−/− macrophages. Notably, IL-1β and NLRP3 mRNA expression were not affected by CATH-2. In addition, CATH-2-induced NLRP3 inflammasome activation was mediated by K+ efflux but independent of the P2X7 receptor that is required for ATP-mediated K+ efflux. Gene interference of NEK7 kinase which has been identified to directly interact with NLRP3, significantly reduced IL-1β secretion and caspase-1 activation induced by CATH-2. Furthermore, confocal microscopy shows that CATH-2 significantly induced lysosomal leakage with the diffusion of dextran fluorescent signal. Cathepsin B inhibitors completely abrogated IL-1β secretion and caspase-1 activation as well as attenuating the formation of ASC specks induced by CATH-2. These results all indicate that CATH-2-induced activation of NLRP3 inflammasome is mediated by K+ efflux, and involves the NEK7 protein and cathepsin B. In conclusion, our study shows that CATH-2 acts as a second signal to activate NLRP3 inflammasome. Our study provides new insight into CATH-2 modulating immune response.
Metabolomic changes in polyunsaturated fatty acids and eicosanoids as diagnostic biomarkers in Mycobacterium avium ssp. paratuberculosis (MAP)-inoculated Holstein–Friesian heifers
Authors: Taylor Emma N. , Beckmann Manfred , Hewinson Glyn , Rooke David , Mur Luis A. J. , Koets Ad P. 
Published: September 2022

AbstractMycobacterium avium subspecies paratuberculosis (MAP) is the causative organism of Johne’s disease, a chronic granulomatous enteritis of ruminants. We have previously used naturally MAP-infected heifer calves to document metabolomic changes occurring in MAP infections. Herein, we used experimentally MAP-inoculated heifer calves to identify biomarkers for MAP infections. At 2-weeks of age, 20 Holstein–Friesian (HF) calves were experimentally inoculated with MAP. These calves, along with 20 control calves, were sampled biweekly up to 13-months of age and then monthly up to 19-months of age. Sera were assessed using flow infusion electrospray high-resolution mass spectrometry (FIE-HRMS) on a Q Exactive hybrid quadrupole-Orbitrap mass spectrometer for high throughput, sensitive, non-targeted metabolite fingerprinting. Partial least squares-discriminate analysis (PLS-DA) and hierarchical cluster analysis (HCA) discriminated between MAP-inoculated and control heifer calves. Out of 34 identified metabolites, six fatty acyls were able to differentiate between experimental groups throughout the study, including 8, 11, 14-eicosatrienoic acid and cis-8, 11, 14, 17-eicosatetraenoic acid which were also detected in our previous study and so further suggested their value as biomarkers for MAP infection. Pathway analysis highlighted the role of the alpha-linoleic acid and linoleic acid metabolism. Within these pathways, two broad types of response, with a rapid increase in some saturated fatty acids and some n-3 polyunsaturated fatty acids (PUFAs) and later n-6 PUFAs, became predominant. This could indicate an initial anti-inflammatory colonisation phase, followed by an inflammatory phase. This study demonstrates the validity of the metabolomic approach in studying MAP infections. Nevertheless, further work is required to define further key events, particularly at a cell-specific level.