bluuebunny/crossref_metadata_2025 huggingface dataset:
Lipase-Catalyzed Synthesis of Glycerol-Free Biodiesel from Rapeseed Oil and Dimethyl Carbonate
Authors: Miao Changlin , Wang Zhongming , Yang Lingmei , Li Huiwen , Lv Pengmei , Zhuang Xinshu , Yuan Zhenhong , Luo Wen
Published: December 2020

The enzymatic production of glycerol-free biodiesel by the transesterification of rapeseed oil was studied using lipase as catalyst. A series of co-solvents were employed in an attempt to improve reaction kinetics. The effects of the reaction conditions (molar ratio of dimethyl carbonate
(DMC) and rapeseed oil, type of lipases, amount of lipases, solvent effects, reaction temperature and time) on the conversion and yield of biodiesel and glycerol carbonate (GC) were investigated. The optimal conditions for biodiesel and GC were 20% Novozym 435, 3:1 molar ratio of DMC to rapeseed
oil, and with 20% [Omim][BF6] as solvent. Under these conditions, the conversions of 88.51% biodiesel and 73.87% GC have been achieved after 48 h. The biodiesel and GC conversions were eight times higher compared to the conventional solvent-free system, respectively. There was no
obvious loss in the biodiesel and GC yield after Novozym 435 having been used for five recycling.
Sulfur-Biological Carbon for Long-Life Room-Temperature Sodium-Sulfur Battery
Authors: Xiao Xiang , Li Wei , Jiang Jianbing
Published: December 2020

Room-temperature sodium-sulfur (RT-Na/S) batteries are gaining much attention particularly in large-scale energy storage due to high theoretical energy density and low cost. However, low conductivity and volume expansion of sulfur, as well as severe shuttle effect of soluble sodium
polysulfides largely hamper their practical applications. Herein, we report an architecture of sulfur embedded in biological carbon (SBC) as cathode for RT-Na/S batteries. The SBC with N, P co-doping biological carbon and hierarchically porous structure afford fast electron and ion transportation,
as well as good mechanical limitation of volume expansion and shuttle effect, therefore achieving excellent cyclic stability (544.7 mAh · g–1 at current density of 200 mA · g –1 after 984 cycles).
The Changing Principles Study of Multiple Parameters in the High Temperature Composting Process with Agricultural Livestock Manure
Authors: Kang Jian , Li Jinping , Feng Lei
Published: December 2020

The reasonable utilization of livestock manure could decrease the utilization of primary energy, possessing huge potential and meaning for sustainable development of economy. In this work, agricultural composting was runned with the material of fresh cow manure, pig manure and chicken
manure as well as the bulking agent of 10% corn straw. The changing trends of parameters such as temperature, pH, the conductivity and the density were mainly studied. It showed that the composting temperature in three composting stages demonstrated a trend of initial increasing and then decreasing.
The composting temperature in boxes of R1, R2 and R3 all exceeded 45 °C on the 3rd d of the composting reaction. On the 6th d of the composting reaction, the temperature of the boxes of R1, R2 and R3 reached the maximum of 65.7, 66.3 and 66.8 °C, respectively, which have satisfied
the requirement of the hygienic standard of the fecal decontamination (GB7959-87). The initial water contents of the composting material of there were 65.28, 66.34 and 64.58%, respectively. The conductivity during experiments demonstrated a change of initial decreasing, then increasing and
final decreasing. The conductivities were stable with values of 1.7, 1.9 and 2.0 S/cm, respectively when the compost is finished. e livestock manure.
Material Composition and Transformation Law of Three Kinds of Livestock and Poultry Manures During the Composting Process
Authors: Zheng Jian , Zhu Chuanyuan , Qi Xingyun , Xiang Peng , Li Yongchun , Wang Yan , Kang Jian
Published: December 2020

This study aimed to investigate the material composition and transformation during composting of different kinds of livestock and poultry manures. Fresh cow manure (R1), pig manure (R2), and chicken manure (R3) were used as raw materials, and 10% corn stalk was selected as the leavening
agent for aerobic static composting. The following results were obtained. After 30 days of aerobic composting, the mass reduction index of the R1, R2, and R3 piles was 48.94%, 47.94%, and 52.94%, respectively. Especially in the first stage (0–10 days) of the composting reaction, the
mass reduction indices of the R1, R2, and R3 piles were significant, which were 21.45%, 22.73%, and 23.73%, respectively. During the composting process, the percentage of dissolved organic carbon in TC showed a downward trend, decreasing to 51.33% ± 1.25%, 57.35% ± 3.21%, and
52.34% ± 2.15%, for R1, R2, and R3, respectively. The percentage of ammonia nitrogen (AN) in total nitrogen (TN) in the piles R1, R2, and R3 first showed an increasing trend and then decreased, showing the highest values of 7.38%, 8.11%, and 9.22%, respectively.
Study on the Kinetics and Pyrolysis Behavior of Waste Containing Urea-Formaldehyde Resins
Authors: Fang Ling , Liu Lin , Luo Siyi , Wang Junzhi , Zuo Zongliang , Peng Bo , Chen Yishan , Yi Chuijie , Sun Wei
Published: December 2020

In this work, we studied the kinetics and behavior of wood panel wastes containing ureaformaldehyde resins. For this purpose, we used a TG-FTIR coupled system to analyze the gaseous products of the pyrolysis. With the results, we obtained the models that provide theoretical evidence
and data support for the studied reactions. According to our findings, the pyrolysis of the ureaformaldehyde components displayed two stages, and the second stage presented a higher intensity. At a temperature of 900 °C, the gas generation rate for hard UF (UF1) was 32.6% higher than that
for soft UF (UF2). When temperature increased from 600 °C to 900 °C, the increase of the gas generation rate was relatively small. In addition, the reaction order was obtained using the CoatsRedfern method, which provided a value for the reaction order of 1.4. The activation energy
of UF1 was slightly higher than that of UF2. The FTIR analysis indicated that the main gaseous products of the pyrolysis of the urea-formaldehyde resin samples were CO2, H2O, and other compounds containing the C–H and the N–H bond as well as carbonyl groups.
In addition, it was determined that Nitrogen was mainly present in the form of hydronitrogen compounds but not as nitrogen oxides. These last may represent a higher degree of pollution.
Study on the Mechanism of Paeoniflorin Against Atherosclerosis Through Network Pharmacology and Molecular Docking
Authors: Zhao Chengguo , Ling Wenpei , Luo Chunyu , Yin Meifang , Qin Shuzhi
Published: December 2020

This study explored the mechanism of paeoniflorin (PF) against atherosclerosis (AS) at the molecular level using network pharmacology and molecular docking. The targets of PF and disease targets related to AS were obtained through literature mining and database search, the PPI network
diagram was drawn, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed, and the PF structure was docked with core target. In the results, 130 common target proteins of PF and AS were obtained. GO enrichment analysis found 1071 items
related to biological processes, mainly related to metabolism, protein modification, regulation of cell activity, regulation of macromolecule synthesis, etc. There were 107 items related to molecular functions, mainly related to cyclic compounds, ions, nucleotides, and ribose Combine etc.
KEGG analysis revealed 79 pathways, mainly Pathways in cancer, PI3K-Akt signalling pathway, Proteoglycans in cancer, Ras signalling pathway, FoxO signalling pathway, etc. The molecular docking results showed that PF had good binding activity with the screened target. In conclusion, this study
indicated that PF treatment of AS involves multiple direct or indirect targets and signal pathways, providing a reference for further research on the mechanism of PF treatment of AS.
Preleukemic and leukemic evolution at the stem cell level
Authors: Stauber Jacob , Greally John M. , Steidl Ulrich
Published: December 2020

Hematological malignancies are an aggregate of diverse populations of cells that arise following a complex process of clonal evolution and selection. Recent approaches have facilitated the study of clonal populations and their evolution over time across multiple phenotypic cell populations. In this review, we present current concepts on the role of clonal evolution in leukemic initiation, disease progression, and relapse. We highlight recent advances and unanswered questions about the contribution of the hematopoietic stem cell population to these processes.
Prolonged rituximab maintenance in follicular lymphoma patients: long-term results of the SAKK 35/03 randomized trial
Authors: Moccia Alden A. , Taverna Christian , Schär Sämi , Vanazzi Anna , Rondeau Stéphanie , Hitz Felicitas , Mingrone Walter , Pabst Thomas , Cevreska Lidija , del Giglio Auro , Raats Johann , Rauch Daniel , Vorobiof Daniel A. , Lohri Andreas , Ruegsegger Céline , Biaggi Rudolf Christine , Rusterholz Corinne , Hayoz Stefanie , Ghielmini Michele , Zucca Emanuele
Published: December 2020

The Swiss Group for Clinical Cancer Research (SAKK) conducted the SAKK 35/03 randomized trial (NCT00227695) to investigate different rituximab monotherapy schedules in patients with follicular lymphoma (FL). Here, we report their long-term treatment outcome. Two-hundred and seventy FL patients were treated with 4 weekly doses of rituximab monotherapy (375 mg/m2); 165 of them, achieving at least a partial response, were randomly assigned to maintenance rituximab (375 mg/m2 every 2 months) on a short-term (4 administrations; n = 82) or a long-term (up to a maximum of 5 years; n = 83) schedule. The primary end point was event-free survival (EFS). At a median follow-up period of 10 years, median EFS was 3.4 years (95% confidence interval [CI], 2.1-5.5) in the short-term arm and 5.3 years (95% CI, 3.5-7.5) in the long-term arm. Using the prespecified log-rank test, this difference is not statistically significant (P = .39). There also was not a statistically significant difference in progression-free survival or overall survival (OS). Median OS was 11.0 years (95% CI, 11.0-NA) in the short-term arm and was not reached in the long-term arm (P = .80). The incidence of second cancers was similar in the 2 arms (9 patients after short-term maintenance and 10 patients after long-term maintenance). No major late toxicities emerged. No significant benefit of prolonged maintenance became evident with longer follow-up. Notably, in symptomatic patients in need of immediate treatment, the 10-year OS rate was 83% (95% CI, 73-89%). These findings indicate that single-agent rituximab may be a valid first-line option for symptomatic patients with advanced FL.
Challenges in chronic transfusion for patients with thalassemia
Authors: Lal Ashutosh
Published: December 2020

The introduction of regular red cell transfusions 60 years ago transformed β-thalassemia major from a fatal childhood illness into a chronic disorder. Further advances in the prevention of transfusion-transmitted infections and management of iron overload have allowed survival and quality of life to approach normal. However, transfusion therapy for some other thalassemia syndromes continues to challenge clinical decision-making. Nearly one-half of the patients with E ß thalassemia are transfusion-dependent, yet the criteria for initiating transfusions or hemoglobin targets are not well defined. Patients with thalassemia intermedia who begin transfusions as adults are at very high risk for developing red cell alloimmunization and serious hemolytic transfusion reactions. In the growing number of survivors of Bart hydrops fetalis, the approach to transfusion therapy and iron chelation is rapidly evolving. A collaboration between hematology and transfusion medicine specialists will be essential to improving patient care and developing evidence-based guidelines.
Can pregnancy-adapted algorithms avoid diagnostic imaging for pulmonary embolism?
Authors: Chan Wee-Shian
Published: December 2020

The low prevalence of pulmonary embolism (PE) among pregnant patients presenting with suspected PE implies that most of these patients will be found not have the disease. Given this low prevalence, excluding PE in this population has necessitated the use of sensitive and specific diagnostic imaging, such as computed tomography pulmonary angiography or ventilation-perfusion scanning. Recent studies suggest that a clinical prediction rule with D-dimer testing can also be used to exclude a subset of pregnant patients with suspected PE without the need for diagnostic imaging. The YEARS criteria, which consist of clinical signs and symptoms of deep venous thrombosis, hemoptysis, and PE as the most likely diagnosis (a subjective variable), combined with selective D-dimer levels, seem to safely exclude up to one-third of these patients without imaging. The revised Geneva rule using objective variables, combined with nonpregnancy cutoffs for D-dimer levels, offers some promise, although fewer patients avoided imaging (14%). These recent studies provide evidence in support of radiation avoidance for some patients; however, for most, imaging remains the only option. Future studies should focus on improving the safety and techniques of imaging modalities, in addition to improving the specificity of D-dimer testing and objective prediction rules. Studies assessing patients’ and physicians’ values, preferences, and risk perceptions are also required to assist clinicians in shared decision making when counseling pregnant patients with suspected PE.
First-generation vs second-generation tyrosine kinase inhibitors: which is best at diagnosis of chronic phase chronic myeloid leukemia?
Authors: Oehler Vivian G.
Published: December 2020

In 2020, for the great majority of patients with chronic phase chronic myeloid leukemia (CML), life expectancy is unaffected by a diagnosis of CML because of the unparalleled efficacy of ABL-targeted tyrosine kinase inhibitors (TKIs) in halting disease progression. A wealth of choices exist for first-line treatment selection, including the first-generation TKI imatinib and the second-generation TKIs bosutinib, dasatinib, and nilotinib. How I select first-line therapy between first-generation and second-generation TKIs is discussed in the context of patient-specific CML disease risk, therapy-related risks, and treatment goals. Although rare, identifying patients with CML at higher risk for disease progression or resistance is important and influences first-line TKI selection. I review the impact of first-generation vs second-generation TKI selection on treatment response and outcomes; the ability to achieve, as well as the timing of, treatment-free remission; and the impact of specific TKIs on longer-term health.
Transformed lymphoma: what should I do now?
Authors: Smith Sonali
Published: December 2020

Although the majority of indolent lymphomas (focusing on follicular lymphoma [FL]) have a prolonged waxing and waning course, a portion of patients experience histologic transformation (HT) to either diffuse large B-cell lymphoma or a higher-grade morphology, often with acquisition of MYC and BCL2 and/or BCL6 rearrangements (high-grade B-cell lymphoma–double-hit lymphoma/triple-hit lymphoma). The overall incidence of HT and transformed follicular lymphoma (tFL) may be declining, but outcomes remain inferior to those in simple indolent lymphoma progression. Recent data suggest that the majority of HT cases occur in higher-risk patients with FL, and they occur early after initial chemoimmunotherapy, comprising the majority of patients with progression of disease within 24 months. This latter point emphasizes the need for a sufficient biopsy at relapse in FL. Treatment options depend on the prior therapy for the indolent component as well as the histology at relapse, but they generally follow several principles discussed in this article. Anthracycline-naïve patients have the best outcomes if there is HT, and responses to R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) are similar to those of patients with de novo diffuse large B-cell lymphoma. Patients with anthracycline exposure prior to transformation have the best outcomes with salvage chemotherapy and a consolidative autologous stem cell transplant. However, a major challenge is the management of patients with tFL who experience relapse early after bendamustine-based treatment, in whom the role of consolidative transplant after anthracycline-based treatment is unclear. In the past several years, cellular therapy has emerged as an important tool for some but not all patients with tFL. This review focuses on the nuances of managing tFL.
Preventing infections in children and adults with asplenia
Authors: Lee Grace M.
Published: December 2020

An estimated 1 million people in the United States have functional or anatomic asplenia or hyposplenia. Infectious complications due to encapsulated organisms such as Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae can lead to fulminant sepsis and death, particularly in young children, in the period shortly after splenectomy, and in immunocompromised patients. Patients with asplenia are also at risk for less common infections due to Capnocytophaga, Babesia, and malaria. Antibiotic prophylaxis, vaccines, and patient and family education are the mainstays of prevention in these at-risk patients. Recommendations for antibiotic prophylaxis typically target high-risk periods, such as 1 to 3 years after splenectomy, children ≤5 years of age, or patients with concomitant immunocompromise. However, the risk for sepsis is lifelong, with infections occurring as late as 40 years after splenectomy. Currently available vaccines recommended for patients with asplenia include pneumococcal vaccines (13-valent pneumococcal conjugate vaccine followed by the 23-valent pneumococcal polysaccharide vaccine), meningococcal vaccines (meningococcal conjugate vaccines for serogroups A, C, Y and W-135 and serogroup B meningococcal vaccines), H. influenzae type b vaccines, and inactivated influenza vaccines. Ongoing booster doses are also recommended for pneumococcal and meningococcal vaccines to maintain protection. Despite the availability of prevention tools, adherence is often a challenge. Dedicated teams or clinics focused on patient education and monitoring have demonstrated substantial improvements in vaccine coverage rates for individuals with asplenia and reduced risk of infection. Future efforts to monitor the quality of care in patients with asplenia may be important to bridge the know–do gap in this high-risk population.
Managing toxicities of Bruton tyrosine kinase inhibitors
Authors: Lipsky Andrew , Lamanna Nicole
Published: December 2020

Inhibition of Bruton’s tyrosine kinase (BTK) has revolutionized the treatment landscape for patients with chronic lymphocytic leukemia (CLL). By targeting this critical kinase in proximal B-cell receptor signaling, BTK inhibitors (BTKis) impair cell proliferation, migration, and activation of NF-κB. Clinically, because indefinite inhibition is a mainstay of therapy, there is an extended period of exposure in which adverse effects can develop. Given the impressive efficacy and activity of BTKis in the treatment of patients with CLL, appropriate management of treatment-emergent adverse events (AEs) is of paramount importance. Here we review the BTKi landscape and present the available toxicity and safety data for each agent. The long-term toxicity profile of ibrutinib, a first-in-class inhibitor, is well characterized and includes a clinically significant incidence of cardiac arrhythmias, bleeding, infection, diarrhea, arthralgias, and hypertension. Acalabrutinib, the initial second-generation BTKi to earn approval from the US Food and Drug Administration, demonstrates improved kinase selectivity for BTK, with commonly observed adverse reactions including infection, headache, and diarrhea. Mediated by both on-target inhibition of BTK and variable off-target inhibition of other kinases including interleukin-2–inducible T-cell kinase (ITK), tyrosine-protein kinase (TEC), and endothelial growth factor receptor (EGFR), the toxicity profile of BTKis is closely linked to their pattern of kinase binding. Other emerging BTKis include second-generation agents with variable degrees of kinase selectivity and third-generation agents that exhibit reversible noncovalent binding to BTK. We also highlight critical considerations for the prevention and monitoring of AEs and offer practical management strategies for treatment-emergent toxicities.
Applied genomics in MPN presentation
Authors: Moliterno Alison R. , Kaizer Hannah
Published: December 2020

Polycythemia vera, essential thrombocytosis (ET), and primary myelofibrosis (PMF) are grouped together as myeloproliferative neoplasms (MPNs) because of shared clinical, pathologic, and molecular features. The 2005 discovery of the driver mutation JAK2V617F, found in more than 70% of individuals with MPNs and 98% of those with PV, has transformed the diagnosis and management of MPNs. Although PV is the most common phenotype associated with JAK2V617F, roughly 60% of individuals with ET or PMF also have the mutation, and JAK2V617F is now recognized as a common lesion in clonal hematopoiesis (CH). JAK2V617F+ CH and MPN are indolent disorders that evolve over time, with transitions to different disease phases, transformation to bone marrow failure or leukemia, and high thrombosis rates. Genomic assessment has taken center stage as an important tool to define disease phenotype, disease burden, prognosis, and even thrombosis risk of MPNs. Genomics has also unveiled the causes and factors that modify the risk of acquiring and expanding CH and MPNs and points to new pathways for targeted therapies to treat and ultimately prevent them. Genomic assessment of patients with MPNs, like other cancers, enables the clinician to capitalize on large population data sets to inform the individual patient of risk, identify treatment, and improve outcomes.
Genomics of myelodysplastic syndrome/myeloproliferative neoplasm overlap syndromes
Authors: Patnaik Mrinal M. , Lasho Terra L.
Published: December 2020

Myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN) overlap syndromes are uniquely classified neoplasms occurring in both children and adults. This category consists of 5 neoplastic subtypes: chronic myelomonocytic leukemia (CMML), juvenile myelomonocytic leukemia (JMML), BCR-ABL1–negative atypical chronic myeloid leukemia (aCML), MDS/MPN-ring sideroblasts and thrombocytosis (MDS/MPN-RS-T), and MDS/MPN-unclassifiable (U). Cytogenetic abnormalities and somatic copy number variations are uncommon; however, >90% patients harbor gene mutations. Although no single gene mutation is specific to a disease subtype, certain mutational signatures in the context of appropriate clinical and morphological features can be used to establish a diagnosis. In CMML, mutated coexpression of TET2 and SRSF2 results in clonal hematopoiesis skewed toward monocytosis, and the ensuing acquisition of driver mutations including ASXL1, NRAS, and CBL results in overt disease. MDS/MPN-RS-T demonstrates features of SF3B1-mutant MDS with ring sideroblasts (MDS-RS), with the development of thrombocytosis secondary to the acquisition of signaling mutations, most commonly JAK2V617F. JMML, the only pediatric entity, is a bona fide RASopathy, with germline and somatic mutations occurring in the oncogenic RAS pathway giving rise to disease. BCR-ABL1–negative aCML is characterized by dysplastic neutrophilia and is enriched in SETBP1 and ETNK1 mutations, whereas MDS/MPN-U is the least defined and lacks a characteristic mutational signature. Molecular profiling also provides prognostic information, with truncating ASXL1 mutations being universally detrimental and germline CBL mutations in JMML showing spontaneous regression. Sequencing information in certain cases can help identify potential targeted therapies (IDH1, IDH2, and splicing mutations) and should be a mainstay in the diagnosis and management of these neoplasms.
Evidence-Based Minireview: Myelodysplastic syndrome/myeloproliferative neoplasm overlap syndromes: a focused review
Authors: Patnaik Mrinal M. , Lasho Terra
Published: December 2020

Myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN) overlap syndromes are unique myeloid neoplasms, with overlapping features of MDS and MPN. They consist of four adult onset entities including chronic myelomonocytic leukemia (CMML), MDS/MPN-ring sideroblasts-thrombocytosis (MDS/MPN-RS-T), BCR-ABL1 negative atypical chronic myeloid leukemia (aCML) and MDS/MPN-unclassifiable (MDS/MPN-U); with juvenile myelomonocytic leukemia (JMML) being the only pediatric onset entity. Among these overlap neoplasms, CMML is the most frequent and is hallmarked by the presence of sustained peripheral blood monocytosis with recurrent mutations involving TET2 (60%), SRSF2 (50%) and ASXL1 (40%); with RAS pathway mutations and JAK2V617F being relatively enriched in proliferative CMML subtypes (WBC ≥13 × 109/L). CMML usually presents in the 7th decade of life, with a male preponderance and is associated with a median overall survival of <36 months. Adverse prognosticators in CMML include increasing age, high WBC, presence of circulating immature myeloid cells, anemia, thrombocytopenia and truncating ASXL1 mutations. While allogeneic stem cell transplantation remains the only curative option, given the late onset of this neoplasm and high frequency of comorbidities, most patients remain ineligible. Hypomethylating agents such as azacitidine, decitabine and oral decitabine/cedazuridine have been US FDA approved for the management of CMML, with overall response rates of 40-50% and complete remission rates of <20%. While these agents epigenetically restore hematopoiesis in a subset of responding patients, they do not impact mutational allele burdens and eventual disease progression to AML remains inevitable. Newer treatment modalities exploiting epigenetic, signaling and splicing abnormalities commonly seen in CMML are much needed.
Immunotherapy with cells (article not eligible for CME credit)
Authors: Chong Elise A. , Porter David L.
Published: December 2020

Both older and newer cell therapies have demonstrated impressive responses in otherwise poor-prognosis lymphomas. Consequently, cellular therapy now plays a major role in the management of many non-Hodgkin lymphomas. In this article, we examine the role of chimeric antigen receptor (CAR) T cells, allogeneic stem cell transplantation, and virus-directed T cells for treatment of lymphomas. We review the current indications for CAR T cells and discuss our clinical approach to selecting and treating patients with aggressive B-cell lymphomas to receive CD19-directed CAR T cells. In addition, we highlight newer cell therapies and provide an overview of promising future approaches that have the potential to transform immunotherapy with cells to treat lymphomas.
The impact of COVID-19 on chronic care according to providers: a qualitative study among primary care practices in Belgium
Authors: Danhieux Katrien , Buffel Veerle , Pairon Anthony , Benkheil Asma , Remmen Roy , Wouters Edwin , van Olmen Josefien
Published: December 2020

Background

The COVID-19 pandemic affects the processes of routine care for chronic patients. A better understanding helps to increase resilience of the health system and prepare adequately for next waves of the pandemic.

Methods

A qualitative study was conducted in 16 primary care practices: 6 solo working, 4 monodisciplinary and 7 multidisciplinary. Twenty-one people (doctors, nurses, dieticians) were interviewed, using semi-structured video interviews. A thematic analysis was done using the domains of the Chronic Care Model (CCM).

Results

Three themes emerged: changes in health care organization, risk stratification and self-management support. All participating practices reported drastic changes in organization with a collective shift towards COVID-19 care, and reduction of chronic care activities, less consultations, and staff responsible for self-management support put on hold. A transition to digital support did not occur. Few practitioners had a systematic approach to identify and contact high-risk patients for early follow-up. A practice with a pre-established structured team collaboration managed to continue most chronic care elements. Generally, practitioners expected no effects of the temporary disruption for patients, although they expressed concern about patients already poorly regulated.

Conclusion

Our findings show a disruption of the delivery of chronic care in the Belgium prim care context. In such contexts, the establishment of the CCM can facilitate continuity of care in crisis times. Short term actions should be directed to facilitate identifying high-risk patients and to develop a practice organization plan to organize chronic care and use digital channels for support, especially to vulnerable patients, during next waves of the epidemic.
An implementation history of primary health care transformation: Alberta’s primary care networks and the people, time and culture of change
Authors: Leslie Myles , Khayatzadeh-Mahani Akram , Birdsell Judy , Forest P. G. , Henderson Rita , Gray Robin Patricia , Schraeder Kyleigh , Seidel Judy , Zwicker Jennifer , Green Lee A.
Published: December 2020

Background

Primary care, and its transformation into Primary Health Care (PHC), has become an area of intense policy interest around the world. As part of this trend Alberta, Canada, has implemented Primary Care Networks (PCNs). These are decentralized organizations, mandated with supporting the delivery of PHC, funded through capitation, and operating as partnerships between the province’s healthcare administration system and family physicians. This paper provides an implementation history of the PCNs, giving a detailed account of howpeople,time, andculturehave interacted to implement bottom up, incremental change in a predominantly Fee-For-Service (FFS) environment.

Methods

Our implementation history is built out of an analysis of policy documents and qualitative interviews. We conducted an interpretive analysis of relevant policy documents (n = 20) published since the first PCN was established. We then grounded 12 semi-structured interviews in that initial policy analysis. These interviews explored 11 key stakeholders’ perceptions of PHC transformation in Alberta generally, and the formation and evolution of the PCNs specifically. The data from the policy review and the interviews were coded inductively, with participants checking our emerging analyses.

Results

Over time, the PCNs have shifted from an initial Frontier Era that emphasized local solutions to local problems and featured few rules, to a present Era of Accountability that features central demands for standardized measures, governance, and co-planning with other elements of the health system. Across both eras, the PCNs have been first and foremost instruments and supporters of family physician authority and autonomy. A core group ofpeopleemerged to create the PCNs and, overtime,to develop a long-term Quality Improvement (QI) vision and governance plan for them as organizations. The continuing willingness of both these groups to work at understanding and aligning one another’sculturesto achieve the transformation towards PHC has been central to the PCNs’ survival and success.

Conclusions

Generalizable lessons from the implementation history of this emerging policy experiment include: The need for flexibility within a broad commitment to improving quality. The importance of time for individuals and organizations to learn about: quality improvement; one another’s cultures; and how best to support the transformation of a system while delivering care locally.
Maternal iodine status in a multi-ethnic UK birth cohort: associations with autism spectrum disorder
Authors: Cromie Kirsten Jade , Threapleton Diane Erin , Snart Charles Jonathan Peter , Taylor Elizabeth , Mason Dan , Wright Barry , Kelly Brian , Reid Stephen , Azad Rafaq , Keeble Claire , Waterman Amanda H. , Meadows Sarah , McKillion Amanda , Alwan Nisreen A. , Cade Janet Elizabeth , Simpson Nigel A. B. , Stewart Paul M. , Zimmermann Michael , Wright John , Waiblinger Dagmar , Mon-Williams Mark , Hardie Laura J. , Greenwood Darren Charles
Published: December 2020

Background

Maternal iodine requirements increase during pregnancy to supply thyroid hormones essential for fetal brain development. Maternal iodine deficiency can lead to hypothyroxinemia, a reduced fetal supply of thyroid hormones which, in the first trimester, has been linked to an increased risk of autism spectrum disorder (ASD) in the child. No study to date has explored the direct link between maternal iodine deficiency and diagnosis of ASD in offspring.

Methods

Urinary iodine concentrations (UIC) and iodine/creatinine ratios (I:Cr) were measured in 6955 mothers at 26–28 weeks gestation participating in the Born in Bradford (BiB) cohort. Maternal iodine status was examined in relation to the probability of a Read (CTV3) code for autism being present in a child’s primary care records through a series of logistic regression models with restricted cubic splines.

Results

Median (inter-quartile range) UIC was 76 μg/L (46, 120) and I:Cr was 83 μg/g (59, 121) indicating a deficient population according to WHO guidelines. Ninety two children (1·3%) in our cohort had received a diagnosis of ASD by the census date. Overall, there was no evidence to support an association between I:Cr or UIC and ASD risk in children aged 8–12 years (p = 0·3).

Conclusions

There was no evidence of an increased clinical ASD risk in children born to mothers with mild-to-moderate iodine deficiency at 26 weeks gestation. Alternative functional biomarkers of exposure and a wider range of conditions may provide further insight.
Accidental apixaban intoxication in a 23-month-old child: a case report
Authors: Launay Manon , Nasser Yara , Maubert Isabelle , Chaux Anne-Cécile , Delavenne Xavier
Published: December 2020

Background

Direct oral anticoagulants, such as apixaban, are increasingly used in everyday practice in order to treat or prevent thromboembolic diseases. To date, there is no available data about apixaban pharmacokinetics in children, and no intoxication has previously been described.

Case presentation

A 23-month-old boy, with no medical history, was admitted to the emergency department 2 h after accidentally ingesting 40 mg apixaban and 0.75 mg digoxin. No adverse event was observed. Digoxin trough level was within therapeutic values. Apixaban blood concentration increased up to 1712 μg/L at H + 6 (1000–2750 μg/L using 2–5 mg/kg of apixaban in adults). The terminal half-life was 8.2 h (6–15 h in adults). The rapid elimination may explain the absence of bleeding despite high concentrations.

Conclusions

Despite an important intake of apixaban and a real disturbance in routine coagulation assays, no clinical sign of bleeding was observed, perhaps due to wide therapeutic range of apixaban. It may also be explained by its rapid elimination. Considering the high Cmax and a possible enteroenteric recycling, the use of activated charcoal should be considered in such situations in order to prevent eventual bleeding.
Navigation-assisted anchor insertion in shoulder arthroscopy: a validity study
Authors: Jung Kyunghwa , Kim Hyojune , Kholinne Erica , Park Dongjun , Choi Hyunseok , Lee Seongpung , Shin Myung-Jin , Kim Dong-Min , Hong Jaesung , Koh Kyoung Hwan , Jeon In-Ho
Published: December 2020

Background

This study aimed to compare conventional and navigation-assisted arthroscopic rotator cuff repair in terms of anchor screw insertion.

Methods

The surgical performance of five operators while using the conventional and proposed navigation-assisted systems in a phantom surgical model and cadaveric shoulders were compared. The participating operators were divided into two groups, the expert group (n = 3) and the novice group (n = 2). In the phantom model, the experimental tasks included anchor insertion in the rotator cuff footprint and sutures retrieval. A motion analysis camera system was used to track the surgeons’ hand movements. The surgical performance metric included the total path length, number of movements, and surgical duration. In cadaveric experiments, the repeatability and reproducibility of the anchor insertion angle were compared among the three experts, and the feasibility of the navigation-assisted anchor insertion was validated.

Results

No significant differences in the total path length, number of movements, and time taken were found between the conventional and proposed systems in the phantom model. In cadaveric experiments, however, the clustering of the anchor insertion angle indicated that the proposed system enabled both novice and expert operators to reproducibly insert the anchor with an angle close to the predetermined target angle, resulting in an angle error of < 2° (P = 0.0002).

Conclusion

The proposed navigation-assisted system improved the surgical performance from a novice level to an expert level. All the experts achieved high repeatability and reproducibility for anchor insertion. The navigation-assisted system may help surgeons, including those who are inexperienced, easily familiarize themselves to of suture anchors insertion in the right direction by providing better guidance for anchor orientation.

Level of evidence

A retrospective study (level 2).
Herpes zoster in patients with sciatica
Authors: Ke Der-Shin , Hsu Chao-Yu , Lin Cheng-Li , Hsu Chung-Y. , Kao Chia-Hung
Published: December 2020

Background

Several diseases are associated with herpes zoster (HZ). However, whether sciatica is a stressor leading to HZ development remains unclear. Here, we evaluated the occurrence of HZ in patients with sciatica.

Methods

The sciatica cohort consisted of patients first diagnosed as having sciatica between 2000 and 2012. All patients with sciatica were randomly age, sex and index year matched with control individuals without sciatica. The primary outcome was diagnosis of HZ. All individuals were followed until HZ diagnosis, withdrawal from the insurance, death, or December 31, 2013, whichever occurred first. HZ risk in the two cohorts was further analyzed with age, sex and comorbidity stratification.

Results

In total, 49,023 patients with sciatica and 49,023 matched controls were included. Female patients were more likely to have HZ development than were male patients [adjusted hazard ratio (HR) = 1.07, 95% confidence interval (CI) = 1.02–1.12]. After adjustments for all the covariates, HZ risk was significantly higher in the sciatica cohort than in the control cohort (adjusted HR = 1.19; 95% CI = 1.12–1.25).

Conclusion

Sciatica increased HZ risk. Thus, HZ risk should be addressed whenever physicians encounter patients with sciatica, HZ vaccination should be considered especially those aged over 50.
A comparison of diet quality indices in a nationally representative cross-sectional study of Iranian households
Authors: Ebrahimi Sara , McNaughton Sarah A. , Leech Rebecca M. , Abdollahi Morteza , Houshiarrad Anahita , Livingstone Katherine M.
Published: December 2020

Background

Iranian diet quality has been evaluated using indices that have not been created based on Iranian dietary guidelines. This study aimed to examine the applicability of two diet quality indices by examining their associations with nutrient adequacy, nutrient intakes and sociodemographics.

Methods

Dietary data were collected using three 24-h dietary recalls from Iranian households. Nutrient adequacy was assessed using World Health Organization/Food and Agriculture Organization 2002 (WHO/FAO) cut points. Household diet quality was calculated using the Healthy Eating Index (HEI) and Diet Quality Index-International (DQI-I). Sociodemographics of the household members were assessed. Regression analyses were used to examine associations between diet quality and nutrient adequacy, and between sociodemographics and diet quality.

Results

A total of 6935 households were included in the analysis. Higher household diet quality was associated with adequate intake of calcium (HEI: OR 1.11, 95% CI: 1.10, 1.13; DQI-I: OR 1.14, 95% CI: 1.13, 1.16), vitamin C (HEI: OR 1.19, 95% CI: 1.17, 1.20; DQI-I: OR 1.12, 95% CI: 1.11, 1.12) and protein (HEI: OR 1.01, 95% CI: 1.00, 1.02; DQI-I: OR 1.09, 95% CI: 1.08, 1.09). Higher household diet quality was associated with household heads who were older (> 56 years old) (HEI: β 2.06, 95% CI: 1.63, 2.50; DQI-I β 2.90, 95% CI: 2.34, 3.45), higher educated (college/university completed) (HEI: β 4.54, 95% CI: 4.02, 5.06; DQI-I: β 2.11, 95% CI: 1.45, 2.77) and living in urban areas (HEI: β 2.85, 95% CI: 2.54, 3.16; DQI-I: β 0.72, 95% CI: 0.32, 1.12).

Conclusions

Based on associations with nutrient adequacy and sociodemographics, the applicability of two diet quality indices for assessing the diet quality of Iranian households was demonstrated. Results also indicated DQI-I may be more applicable than HEI for evaluating Iranian nutrient adequacy. Findings have implications for the design and assessment of diet quality in Iranian populations. Future research should examine the link between these diet quality indices and health outcomes.
Does social support moderate the association between hunger and mental health in youth? A gender-specific investigation from the Canadian Health Behaviour in School-aged Children study
Authors: Hammami Nour , Leatherdale Scott T. , Elgar Frank J.
Published: December 2020

Background

Youth who go hungry have poorer mental health than their counterparts – there are gender differences in this relationship. This study investigated the role of social support in the association between hunger and mental health among a nationally representative sample of youth in Canada in gender-specific analyses.

Methods

We used a probability-based sample of 21,750 youth in grades 6–10 who participated in the 2017–2018 Canadian Health Behaviour in School-aged Children. Self-report data were gathered on hunger, mental health (measured via the World Health Organization-5 well-being index) and five sources of support – peer, family and teacher support as well as the school climate and neighborhood support. We conducted adjusted, gender-specific, multilevel regression analyses assessing the association between mental health, social support and hunger.

Results

We found that youth who reported lower support were more likely to experience going to bed hungry (relative to never hungry) across all support factors. As for the social support factors, all the social support factors were associated with a higher mental health score, even after controlling for hunger. Despite these results our final set of models showed that our measures of social support did not alleviate the negative association between hunger and mental health. As for gender-specific findings, the negative association between hunger and a mental health was more pronounced among females relative to their male counterparts. We also found that certain social support factors (i.e., family, teacher and neighborhood support) were associated with a higher mental health score among females relative to males while controlling for hunger status.

Conclusions

We find that five social support factors are associated with a higher mental health score among ever hungry youth; however, social support did not overpower the negative association between hunger and mental health. Food insecurity is a challenge to address holistically; however, hungry youth who have high social support have higher odds of better mental health.
Correction to: Consumption of non-nutritive sweeteners by pre-schoolers of the food and environment Chilean cohort (FECHIC) before the implementation of the Chilean food labelling and advertising law
Authors: Hargous Carolina Venegas , Reyes Marcela , Taillie Lindsey Smith , González Carmen Gloria , Corvalán Camila
Published: December 2020

An amendment to this paper has been published and can be accessed via the original article.
Feasibility of satellite image and GIS sampling for population representative surveys: a case study from rural Guatemala
Authors: Miller Ann C. , Rohloff Peter , Blake Alexandre , Dhaenens Eloin , Shaw Leah , Tuiz Eva , Grandesso Francesco , Mendoza Montano Carlos , Thomson Dana R.
Published: December 2020

Background

Population-representative household survey methods require up-to-date sampling frames and sample designs that minimize time and cost of fieldwork especially in low- and middle-income countries. Traditional methods such as multi-stage cluster sampling, random-walk, or spatial sampling can be cumbersome, costly or inaccurate, leading to well-known biases. However, a new tool, Epicentre’s Geo-Sampler program, allows simple random sampling of structures, which can eliminate some of these biases. We describe the study design process, experiences and lessons learned using Geo-Sampler for selection of a population representative sample for a kidney disease survey in two sites in Guatemala.

Results

We successfully used Epicentre’s Geo-sampler tool to sample 650 structures in two semi-urban Guatemalan communities. Overall, 82% of sampled structures were residential and could be approached for recruitment. Sample selection could be conducted by one person after 30 min of training. The process from sample selection to creating field maps took approximately 40 h.

Conclusion

In combination with our design protocols, the Epicentre Geo-Sampler tool provided a feasible, rapid and lower-cost alternative to select a representative population sample for a prevalence survey in our semi-urban Guatemalan setting. The tool may work less well in settings with heavy arboreal cover or densely populated urban settings with multiple living units per structure. Similarly, while the method is an efficient step forward for including non-traditional living arrangements (people residing permanently or temporarily in businesses, religious institutions or other structures), it does not account for some of the most marginalized and vulnerable people in a population–the unhoused, street dwellers or people living in vehicles.
The complex relationship between MITF and the immune system: a Melanoma ImmunoTherapy (response) Factor?
Authors: Ballotti Robert , Cheli Yann , Bertolotto Corine
Published: December 2020

The clinical benefit of immune checkpoint inhibitory therapy (ICT) in advanced melanomas is limited by primary and acquired resistance. The molecular determinants of the resistance have been extensively studied, but these discoveries have not yet been translated into therapeutic benefits. As such, a paradigm shift in melanoma treatment, to surmount the therapeutic impasses linked to the resistance, is an important ongoing challenge.

This review outlines the multifaceted interplay between microphthalmia-associated transcription factor (MITF), a major determinant of the biology of melanoma cells, and the immune system. In melanomas, MITF functions downstream oncogenic pathways and microenvironment stimuli that restrain the immune responses. We highlight how MITF, by controlling differentiation and genome integrity, may regulate melanoma-specific antigen expression by interfering with the endolysosomal pathway, KARS1, and antigen processing and presentation. MITF also modulates the expression of coinhibitory receptors, i.e., PD-L1 and HVEM, and the production of an inflammatory secretome, which directly affects the infiltration and/or activation of the immune cells.

Furthermore, MITF is also a key determinant of melanoma cell plasticity and tumor heterogeneity, which are undoubtedly one of the major hurdles for an effective immunotherapy. Finally, we briefly discuss the role of MITF in kidney cancer, where it also plays a key role, and in immune cells, establishing MITF as a central mediator in the regulation of immune responses in melanoma and other cancers.

We propose that a better understanding of MITF and immune system intersections could help in the tailoring of current ICT in melanomas and pave the way for clinical benefits and long-lasting responses.