bluuebunny/crossref_metadata_2025_split huggingface dataset:
Strengthening global health security – lessons learned from public health England’s international health regulations strengthening project
Authors: Carlson Cindy , Shorten Tim , Khalid Asma , Cooper Matthew , Sherratt Ruth , Voltolina Giovanna 
Published: February 2022

Abstract
Background
Country experiences of responding to the challenges of COVID-19 in 2020 highlighted how critical it is to have strong, in-country health security capacity. The UK government has invested in health security capacity development through various projects and agencies, including the UK Department of Health and Social Care, whose Global Health Security Programme provides funding to Public Health England (PHE) to implement health security support. This article describes the results and conclusions of the midterm evaluation, undertaken by Itad, of one of Public Health England’s global health projects: International Health Regulations Strengthening, which operates across six countries and works with the Africa Centres for Disease Control. It also highlights some of the key lessons learned for the benefit of other agencies moving into supporting national health security efforts.

Results
The Itad team found strong evidence that the IHR Project is well aligned with, and responding to, partners’ capability strengthening needs and that the three workstreams – systems coordination, workforce development and technical systems strengthening are implementing relevant and appropriate action to support national priorities. The IHR Project is also aligned with and complementary to other relevant UK development assistance although the Project could strengthen the strategic collaboration with WHO, US CDC and other UK government projects in countries. The Itad team also found that the IHR Project could be more effective if the technical assistance activities were accompanied by relevant materials and equipment while maintaining its supportive role. There was evidence of where technical assistance in the form of training and follow-up mentoring had led to improvements in practice and in IHR compliance, but these were not being systematically captured by the Project’s routine reporting.

Conclusions
There was good evidence that the project was doing the right things and aligning its work in the right way, with more limited evidence at the time of the midterm evaluation that it was making progress towards achieving the right results.
Response assessment after stereotactic body radiation therapy for spine and non-spine bone metastases: results from a single institutional study
Authors: Correia Dora , Moullet Barbara , Cullmann Jennifer , Heiss Rafael , Ermiş Ekin , Aebersold Daniel M. , Hemmatazad Hossein 
Published: February 2022

Abstract
Background
The use of stereotactic body radiation therapy (SBRT) for tumor and pain control in patients with bone metastases is increasing. We report response assessment after bone SBRT using radiological changes through time and clinical examination of patients.

Methods
We analyzed retrospectively oligo-metastatic/progressive patients with bony lesions treated with SBRT between 12/2008 and 10/2018, without in-field re-irradiation, in our institution. Radiological data were obtained from imaging modalities used for SBRT planning and follow-up purposes in picture archiving and communication system and assessed by two independent radiologists blind to the time of treatment. Several radiological changes were described. Radiographic response assessment was classified according to University of Texas MD Anderson Cancer Center criteria. Pain response and the neurological deficit were captured before and at least 6 months after SBRT.

Results
A total of 35 of the 74 reviewed patients were eligible, presenting 43 bone metastases, with 51.2% (n = 22) located in the vertebral column. Median age at the time of SBRT was 66 years (range 38–84) and 77.1% (n = 27) were male. Histology was mainly prostate (51.4%, n = 18) and breast cancer (14.3%, n = 5). Median total radiation dose delivered was 24 Gy (range 24–42), in three fractions (range 2–7), prescribed to 70–90% isodose-line. After a median follow-up of 1.8 years (range < 1–8.2) for survivors, complete or partial response, stable, and progressive disease occurred in 0%, 11.4% (n = 4), 68.6% (n = 24), and 20.0% (n = 7) of the patients, respectively. Twenty patients (57.1%) died during the follow-up time, all from disease progression, yet 70% (n = 14) from this population with local stable disease after SBRT. From patients who were symptomatic and available for follow-up, almost half (44.4%) reported pain reduction after SBRT.

Conclusions
Eighty percent of the patients showed local control after SBRT for bone metastases. Pain response was favorable. For more accurate response assessment, comparing current imaging modalities with advanced imaging techniques such as functional MRI and PET/CT, in a prospective and standardized way is warranted.
Trial registration Retrospectively registered.
Genetic findings of Sanger and nanopore single-molecule sequencing in patients with X-linked hearing loss and incomplete partition type III
Authors: Chen Ying , Qiu Jiajun , Wu Yingwei , Jia Huan , Jiang Yi , Jiang Mengda , Wang Zhili , Sheng Hai-Bin , Hu Lingxiang , Zhang Zhihua , Wang Zhaoyan , Li Yun , Huang Zhiwu , Wu Hao 
Published: February 2022

Abstract
Background
POU3F4 is the causative gene for X-linked deafness-2 (DFNX2), characterized by incomplete partition type III (IP-III) malformation of the inner ear. The purpose of this study was to investigate the clinical characteristics and molecular findings in IP-III patients by Sanger or nanopore single-molecule sequencing.

Methods
Diagnosis of IP-III was mainly based on clinical characteristics including radiological and audiological findings. Sanger sequencing of POU3F4 was carried out for these IP-III patients. For those patients with negative results for POU3F4 Sanger sequencing, nanopore long-read single-molecule sequencing was used to identify the possible pathogenic variants. Hearing intervention outcomes of hearing aids (HAs) fitting and cochlear implantation (CI) were also analyzed. Aided pure tone average (PTA) was further compared between two groups of patients according to their different locations of POU3F4 variants: in the exon region or in the upstream region.

Results
In total, 18 male patients from 14 unrelated families were diagnosed with IP-III. 10 variants were identified in POU3F4 by Sanger sequencing and 6 of these were reported for the first time (p.Gln181*, p.Val215Gly, p.Arg282Gln, p.Gln316*, c.903_912 delins TGCCA and p.Arg205del). Four different deletions that varied from 80 to 486 kb were identified 876–1503 kb upstream of POU3F4 by nanopore long-read single-molecule sequencing. De novo genetic mutations occurred in 21.4% (3/14) of patients with POU3F4 mutations. Among these 18 patients, 7 had bilateral HAs and 10 patients received unilateral CI. The mean aided PTA for HAs and CI users were 41.1 ± 5.18 and 40.3 ± 7.59 dB HL respectively. The mean PTAs for patients with the variants located in the exon and upstream regions were 39.6 ± 6.31 versus 43.0 ± 7.10 dB HL, which presented no significant difference (p = 0.342).

Conclusions
Among 14 unrelated IP-III patients, 28.6% (4/14) had no definite mutation in exon region of POU3F4. However, possible pathogenic deletions were identified in upstream region of this gene. De novo genetic mutations occurred in 21.4% (3/14) of patients with POU3F4 mutation. There was no significant difference of hearing intervention outcomes between the IP-III patients with variants located in the exon region and in the upstream region.
Health systems resilience in fragile and shock-prone settings through the prism of gender equity and justice: implications for research, policy and practice
Authors: Mansour Wesam , Arjyal Abriti , Hughes Chad , Gbaoh Emma Tiange , Fouad Fouad Mohamed , Wurie Haja , Kyaw Hnin Kalayar , Tartaggia Julie , Hawkins Kate , Than Kyu Kyu , Kallon Lansana Hassim , Saad Maya Abou , Chand Obindra , Win Phone Myint , Yamout Rouham , Regmi Shophika , Baral Sushil , Theobald Sally , Raven Joanna 
Published: February 2022

AbstractFragile and shock-prone settings (FASP) present a critical development challenge, eroding efforts to build healthy, sustainable and equitable societies. Power relations and inequities experienced by people because of social markers, e.g., gender, age, education, ethnicity, and race, intersect leading to poverty and associated health challenges. Concurrent to the growing body of literature exploring the impact of these intersecting axes of inequity in FASP settings, there is a need to identify actions promoting gender, equity, and justice (GEJ). Gender norms that emphasise toxic masculinity, patriarchy, societal control over women and lack of justice are unfortunately common throughout the world and are exacerbated in FASP settings. It is critical that health policies in FASP settings consider GEJ and include strategies that promote progressive changes in power relationships. ReBUILD for Resilience (ReBUILD) focuses on health systems resilience in FASP settings and is underpinned by a conceptual framework that is grounded in a broader view of health systems as complex adaptive systems. The framework identifies links between different capacities and enables identification of feedback loops which can drive or inhibit the emergence and implementation of resilient approaches. We applied the framework to four different country case studies (Lebanon, Myanmar, Nepal and Sierra Leone) to illustrate how it can be inclusive of GEJ concerns, to inform future research and support context responsive recommendations to build equitable and inclusive health systems in FASP settings.
Impact of platelet transfusion on outcomes in trauma patients
Authors: Hamada S. R. , Garrigue D. , Nougue H. , Meyer A. , Boutonnet M. , Meaudre E. , Culver A. , Gaertner E. , Audibert G. , Vigué B. , Duranteau J. , Godier A. ,   and the TraumaBase Group, Abback Paer-Selim , Audibert Gérard , Gauss Tobias , Geeraerts Thomas , Harrois Anatole , Langeron Olivier , Leone Marc , Pottecher Julien , Stecken Laurent , Hanouz Jean-Luc 
Published: February 2022

Abstract
Background
Trauma-induced coagulopathy includes thrombocytopenia and platelet dysfunction that impact patient outcome. Nevertheless, the role of platelet transfusion remains poorly defined. The aim of the study was 1/ to evaluate the impact of early platelet transfusion on 24-h all-cause mortality and 2/ to describe platelet count at admission (PCA) and its relationship with trauma severity and outcome.

Methods
Observational study carried out on a multicentre prospective trauma registry. All adult trauma patients directly admitted in participating trauma centres between May 2011 and June 2019 were included. Severe haemorrhage was defined as ≥ 4 red blood cell units within 6 h and/or death from exsanguination. The impact of PCA and early platelet transfusion (i.e. within the first 6 h) on 24-h all-cause mortality was assessed using uni- and multivariate logistic regression.

Results
Among the 19,596 included patients, PCA (229 G/L [189,271]) was associated with coagulopathy, traumatic burden, shock and bleeding severity. In a logistic regression model, 24-h all-cause mortality increased by 37% for every 50 G/L decrease in platelet count (OR 0.63 95% CI 0.57–0.70; p < 0.001). Regarding patients with severe hemorrhage, platelets were transfused early for 36% of patients. Early platelet transfusion was associated with a decrease in 24-h all-cause mortality (versus no or late platelets): OR 0.52 (95% CI 0.34–0.79; p < 0.05).

Conclusions
PCA, although mainly in normal range, was associated with trauma severity and coagulopathy and was predictive of bleeding intensity and outcome. Early platelet transfusion within 6 h was associated with a decrease in mortality in patients with severe hemorrhage. Future studies are needed to determine which doses of platelet transfusion will improve outcomes after major trauma.
Treatment of COVID-19-associated ARDS with mesenchymal stromal cells: a multicenter randomized double-blind trial
Authors: Monsel Antoine , Hauw-Berlemont Caroline , Mebarki Miryam , Heming Nicholas , Mayaux Julien , Nguekap Tchoumba Otriv , Diehl Jean-Luc , Demoule Alexandre , Annane Djillali , Marois Clémence , Demeret Sophie , Weiss Emmanuel , Voiriot Guillaume , Fartoukh Muriel , Constantin Jean-Michel , Mégarbane Bruno , Plantefève Gaëtan , Malard-Castagnet Stéphanie , Burrel Sonia , Rosenzwajg Michelle , Tchitchek Nicolas , Boucher-Pillet Hélène , Churlaud Guillaume , Cras Audrey , Maheux Camille , Pezzana Chloé , Diallo Mamadou Hassimiou , Ropers Jacques , Menasché Philippe , Larghero Jérôme ,   APHP STROMA–CoV-2 Collaborative Research Group, Benchetrit Déborah , Bonvallot Harold , Charbonnier-Beaupel Fanny , Dhib-Charfi Meriem , Delmotte Pierre Romain , Kone Assitan , Le Corre Marine , Marcelin Anne-Geneviève , Metz Carole , Puybasset Louis , Salem Joe-Elie , Vezinet Corinne 
Published: February 2022

Abstract
Background
Severe acute respiratory syndrome coronavirus-2 (SARS–CoV-2)-induced acute respiratory distress syndrome (ARDS) causes high mortality. Umbilical cord-derived mesenchymal stromal cells (UC-MSCs) have potentially relevant immune-modulatory properties, whose place in ARDS treatment is not established. This phase 2b trial was undertaken to assess the efficacy of UC-MSCs in patients with SARS–CoV-2-induced ARDS.

Methods
This multicentre, double-blind, randomized, placebo-controlled trial (STROMA–CoV-2) recruited adults (≥ 18 years) with SARS–CoV-2-induced early (< 96 h) mild-to-severe ARDS in 10 French centres. Patients were randomly assigned to receive three intravenous infusions of 106 UC-MSCs/kg or placebo (0.9% NaCl) over 5 days after recruitment. For the modified intention-to-treat population, the primary endpoint was the partial pressure of oxygen to fractional inspired oxygen (PaO2/FiO2)-ratio change between baseline (day (D) 0) and D7.

Results
Among the 107 patients screened for eligibility from April 6, 2020, to October 29, 2020, 45 were enrolled, randomized and analyzed. PaO2/FiO2 changes between D0 and D7 did not differ significantly between the UC-MSCs and placebo groups (medians [IQR] 54.3 [− 15.5 to 93.3] vs 25.3 [− 33.3 to 104.6], respectively; ANCOVA estimated treatment effect 7.4, 95% CI − 44.7 to 59.7; P = 0.77). Six (28.6%) of the 21 UC-MSCs recipients and six of 24 (25%) placebo-group patients experienced serious adverse events, none of which were related to UC-MSCs treatment.

Conclusions
D0-to-D7 PaO2/FiO2 changes for intravenous UC-MSCs-versus placebo-treated adults with SARS–CoV-2-induced ARDS did not differ significantly. Repeated UC-MSCs infusions were not associated with any serious adverse events during treatment or thereafter (until D28). Larger trials enrolling patients earlier during the course of their ARDS are needed to further assess UC-MSCs efficacy in this context.
Trial registration: NCT04333368. Registered 01 April 2020, https://clinicaltrials.gov/ct2/history/NCT04333368.
A core of differentially methylated CpG loci in gMDSCs isolated from neonatal and adult sources
Authors: Berglund-Brown Isabella , Nissen Emily , Koestler Devin C. , Butler Rondi A. , Eliot Melissa N. , Padbury James F. , Salas Lucas A. , Molinaro Annette M. , Christensen Brock C. , Wiencke John K. , Kelsey Karl T. 
Published: February 2022

AbstractBackgroundMyeloid-derived suppressor cells (MDSCs), which include monocytic (mMDSCs) and granulocytic (gMDSCs) cells, are an immunosuppressive, heterogeneous population of cells upregulated in cancer and other pathologic conditions, in addition to normal conditions of stress. The origin of MDSCs is debated, and the regulatory pattern responsible for gMDSC differentiation remains unknown. Since DNA methylation (DNAm) contributes to lineage differentiation, we have investigated whether it contributes to the acquisition of the gMDSC phenotype.ResultsUsing the Illumina EPIC array to measure DNAm of gMDSCs and neutrophils from diverse neonatal and adult blood sources, we found 189 differentially methylated CpGs between gMDSCs and neutrophils with a core of ten differentially methylated CpGs that were consistent across both sources of cells. Genes associated with these loci that are involved in immune responses includeVCL, FATS, YAP1, KREMEN2, UBTF,MCC-1, andEFCC1. In two cancer patient groups that reflected those used to develop the methylation markers (head and neck squamous cell carcinoma (HNSCC) and glioma), all of the CpG loci were differentially methylated, reaching statistical significance in glioma cases and controls, while one was significantly different in the smaller HNSCC group.ConclusionsOur findings indicate that gMDSCs have a core of distinct DNAm alterations, informing future research on gMDSC differentiation and function.
Activated phosphoinositide 3-kinase δ syndrome associated with nephromegaly, growth hormone deficiency, bronchiectasis: a case report
Authors: Craig Megan , Geng Bob , Wigby Kristen , Phillips Susan A. , Bakhoum Christine , Naheedy John , Cernelc-Kohan Mateja 
Published: February 2022

Abstract
Background
Activated phosphoinositide 3-kinase (PI3K) δ syndrome (APDS) is a rare form of primary immunodeficiency with 243 known cases reported in the literature. Known findings associated with the condition include recurrent sinusitis and bronchitis, bronchiectasis, immune cytopenias, mild developmental delay, splenomegaly, and lymphadenopathy. We report the case of a child with APDS accompanied by unique clinical features: nephromegaly and growth hormone deficiency with associated pituitary anatomic abnormality.

Case presentation
The patient is a nine-year-old boy with a heterozygous de novo variant in phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit δ (p.E1021K), previously reported in association with APDS. Our patient, who had no family history of immunodeficiency, exhibits classic findings of this syndrome but also has unique features that extend the phenotypic spectrum of this disorder. At 5 years of age, the patient showed marked growth deceleration and was demonstrated to have growth hormone (GH) deficiency with associated pituitary anatomic abnormality. He started GH therapy with an excellent response. He additionally has bilateral nephromegaly of unclear etiology, microscopic hematuria and proteinuria, asthma, and has developed left hip pain with arthrocentesis consistent with oligoarticular juvenile idiopathic arthritis. At age nine, the patient was referred to genetics and whole exome sequencing revealed APDS. Though there was initial concern that GH may increase risk for malignancy as GH signals through the PI3K pathway, he was allowed to continue treatment as the PI3K pathway was considered constitutively active at baseline.

Conclusions
Our patient’s unique presentation adds to the clinical information regarding APDS, demonstrates the utility of genetic testing and illustrates the importance of a multidisciplinary collaborative approach in managing this complex syndrome.
Telemedicine in allergy/immunology in the era of COVID-19: a Canadian perspective
Authors: Edgerley Sarah , Zhu Rongbo , Quidwai Ariba , Kim Harold , Jeimy Samira 
Published: February 2022

Abstract
Background
In the era of COVID-19, utilization of telemedicine has dramatically increased. In addition to reduced travel times, patient expenses, and work or school days missed, telemedicine allows clinicians to provide continued care while minimizing face-to-face interactions, maintaining social distancing, and limiting potential COVID-19 exposures. Clinical Immunology and Allergy (CIA), like many specialties, has adapted to incorporate telemedicine into practice. Previous studies have demonstrated similar patient satisfaction between virtual and in-person visits. However, evidence from fully publicly funded health care systems such as Canada has been limited.

Methods
We performed a quality improvement (QI) initiative to assess the feasibility of telemedicine. Between 1 March and 30 September 2020, patient encounters of two academic allergists at a single institution in London, Ontario, Canada were analyzed. Assessments were categorized into in-person or telemedicine appointments. A random sample of patients assessed virtually completed a voluntary patient satisfaction survey. Qualitative analysis was performed on survey comments.

Results
In total 3342 patients were seen. The majority were adults (n = 2162, or 64.7%) and female (n = 1872, or 56%). 1543 (46.2%) assessments were virtual and 1799 (53.8%) assessments were in-person. 67 of 100 random patient surveys sent to those in the virtual assessment group were completed. 89.6% (n = 60) agreed or strongly agreed when asked if they were satisfied with their telemedicine visit. 64.2% (n = 43) felt they received the same level of care compared to in-person assessments and 91% (n = 61) stated they would attend another virtual appointment. 95.4% (n = 62) of patients reported saving time with virtual assessment, the majority (n = 42, 62.7%) estimating between 1–4 h saved. Reported shortcomings included technical difficulties, “feeling rushed”, and missing in-person interactions.

Conclusions
Our quality improvement initiative demonstrated high patient satisfaction and time savings with virtual assessment in a publicly funded health care system. Studies suggest that CIA may be uniquely situated to benefit from permanent integration of virtual care into regular practice for both new and follow-up appointments. We anticipate continued increased utilization of telemedicine, signifying a lasting beneficial change in the delivery of healthcare.
A refractory tenosynovitis of the wrist: a case report
Authors: Boudon Alex , Opota Onya , Dan Diana 
Published: February 2022

Abstract
Background
Mycobacterium malmoense is a species of slow-growing nontuberculous mycobacteria. It causes mostly pulmonary infections or lymphadenitis in children, but is increasingly encountered in isolated tenosynovitis in adults. Diagnosis is often delayed because of the rarity of the condition and the difficulty of culturing the bacteria.

Case presentation
We report on a rare association of seronegative polyarthritis with infectious nontuberculous mycobacteria tenosynovitis. A 65-year-old Caucasian female was referred to our clinic because of persisting tenosynovitis of the finger flexor tendons of her right hand, despite two previous synovectomies. She also reported bilateral shoulder and left wrist pain. Paraclinical investigations showed slightly elevated inflammatory parameters. Ultrasound showed synovitis of metacarpophalangeal joints of the right hand and right knee, and a bilateral subacromial bursitis. Hand magnetic resonance imaging also revealed an erosive carpal synovitis. Bacteriological analysis of the second tenosynovectomy specimen showed no growths in aerobic and anaerobic cultures. An additional synovial fluid analysis of the wrist joint was negative for mycobacteria and crystals. Seronegative polyarthritis was suspected, but the initiated immunosuppressive treatment with prednisolone and methotrexate resulted in no clinical improvement of the tenosynovitis. Yet the other joints responded well, and the inflammatory parameters normalized. The immunosuppression was later stopped because of side effects. Due to massive worsening of the tenosynovitis, a third synovectomy was performed. Mycobacterium malmoense was identified on biopsy, leading to the diagnosis of infectious tenosynovitis. At this point, we started an antituberculous therapy, with incomplete response. A combination of antimicrobial and immunosuppressive treatment finally led to the desired clinical improvement.

Conclusion
The treatment of nontuberculous mycobacteria tenosynovitis is not well established, but combining antibiotics with surgical debridement is probably the most adequate approach. Our case highlights the importance of having a high clinical suspicion of an atypical infection in patients with inflammatory tenosynovitis not responding to usual care.