bluuebunny/crossref_metadata_2025_split huggingface dataset:
Health services availability and readiness moderate cash transfer impacts on health insurance enrolment: evidence from the LEAP 1000 cash transfer program in Ghana
Authors: Otieno Peter , Angeles Gustavo , Quiñones Sarah , van Halsema Vincent , Novignon Jacob , Palermo Tia ,   the LEAP 1000 Evaluation Team, Palermo Tia , de Groot Richard , Valli Elsa , Osei-Akoto Isaac , Adamba Clement , K. Darko Joseph , Darko Osei Robert , Dompae Francis , Yaw Nana , Handa Sudhanshu , Barrington Clare , Abdoulayi Sara , Angeles Gustavo , Chakrabarti Averi , Otchere Frank , J. Akaligaung Akalpa , Aborigo Raymond 
Published: May 2022

Abstract
Background
Expanding health insurance coverage is a priority under Sustainable Development Goal 3. To address the intersection between poverty and health and remove cost barriers, the government of Ghana established the National Health Insurance Scheme (NHIS). Government further linked NHIS with the Livelihood Empowerment Against Poverty (LEAP) 1000 cash transfer program by waiving premium fees for LEAP 1000 households. This linkage led to increased NHIS enrolment, however, large enrolment gaps remained. One potential reason for failure to enroll may relate to the poor quality of health services.

Methods
We examine whether LEAP 1000 impacts on NHIS enrolment were moderated by health facilities’ service availability and readiness.

Results
We find that adults in areas with the highest service availability and readiness are 18 percentage points more likely to enroll in NHIS because of LEAP 1000, compared to program effects of only 9 percentage points in low service availability and readiness areas. Similar differences were seen for enrolment among children (20 v. 0 percentage points) and women of reproductive age (25 v. 10 percentage points).

Conclusions
We find compelling evidence that supply-side factors relating to service readiness and availability boost positive impacts of a cash transfer program on NHIS enrolment. Our work suggests that demand-side interventions coupled with supply-side strengthening may facilitate greater population-level benefits down the line. In the quest for expanding financial protection towards accelerating the achievement of universal health coverage, policymakers in Ghana should prioritize the integration of efforts to simultaneously address demand- and supply-side factors.

Trial registration
This study is registered in the International Initiative for Impact Evaluation’s (3ie) Registry for International Development Impact Evaluations (RIDIE-STUDY-ID-55942496d53af).
Analysis of host-pathogen gene association networks reveals patient-specific response to streptococcal and polymicrobial necrotising soft tissue infections
Authors: Jahagirdar Sanjeevan , Morris Lorna , Benis Nirupama , Oppegaard Oddvar , Svenson Mattias , Hyldegaard Ole , Skrede Steinar , Norrby-Teglund Anna ,   INFECT Study group, Bruun Trond , Rath Eivind , Nedrebø Torbjørn , Arnell Per , Rosen Anders , Hedetoft Morten , Madsen Martin B. , Svensson Mattias , Snäll Johanna , Karlsson Ylva , Nekludov Michael , Martins dos Santos Vitor A. P. , Saccenti Edoardo 
Published: May 2022

﻿AbstractBackgroundNecrotising soft tissue infections (NSTIs) are rapidly progressing bacterial infections usually caused by either several pathogens in unison (polymicrobial infections) orStreptococcus pyogenes(mono-microbial infection). These infections are rare and are associated with high mortality rates. However, the underlying pathogenic mechanisms in this heterogeneous group remain elusive.MethodsIn this study, we built interactomes at both the population and individual levels consisting of host-pathogen interactions inferred from dual RNA-Seq gene transcriptomic profiles of the biopsies from NSTI patients.ResultsNSTI type-specific responses in the host were uncovered. TheS. pyogenesmono-microbial subnetwork was enriched with host genes annotated with involved in cytokine production and regulation of response to stress. The polymicrobial network consisted of several significant associations between different species (S. pyogenes,Porphyromonas asaccharolyticaandEscherichia coli) and host genes. The host genes associated withS. pyogenesin this subnetwork were characterised by cellular response to cytokines. We further found several virulence factors including hyaluronan synthase, Sic1, Isp, SagF, SagG, ScfAB-operon, Fba and genes upstream and downstream of EndoS along with bacterial housekeeping genes interacting with the human stress and immune response in various subnetworks between host and pathogen.ConclusionsAt the population level, we found aetiology-dependent responses showing the potential modes of entry and immune evasion strategies employed byS. pyogenes, congruent with general cellular processes such as differentiation and proliferation. After stratifying the patients based on the subject-specific networks to study the patient-specific response, we observed different patient groups with different collagens, cytoskeleton and actin monomers in association with virulence factors, immunogenic proteins and housekeeping genes which we utilised to postulate differing modes of entry and immune evasion for different bacteria in relationship to the patients’ phenotype.
Broad humoral and cellular immunity elicited by one-dose mRNA vaccination 18 months after SARS-CoV-2 infection
Authors: Kang Chang Kyung , Shin Hyun Mu , Choe Pyoeng Gyun , Park Jiyoung , Hong Jisu , Seo Jung Seon , Lee Yung Hie , Chang Euijin , Kim Nam Joong , Kim Minji , Kim Yong-Woo , Kim Hang-Rae , Lee Chang-Han , Seo Jun-Young , Park Wan Beom , Oh Myoung-don 
Published: May 2022

Abstract
Background
Practical guidance is needed regarding the vaccination of coronavirus disease 2019 (COVID-19) convalescent individuals in resource-limited countries. It includes the number of vaccine doses that should be given to unvaccinated patients who experienced COVID-19 early in the pandemic.

Methods
We recruited COVID-19 convalescent individuals who received one or two doses of an mRNA vaccine within 6 or around 18 months after a diagnosis of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection. Their samples were assessed for IgG-binding or neutralizing activity and cell-mediated immune responses against SARS-CoV-2 wild-type and variants of concern.

Results
A total of 43 COVID-19 convalescent individuals were analyzed in the present study. The results showed that humoral and cellular immune responses against SARS-CoV-2 wild-type and variants of concern, including the Omicron variant, were comparable among patients vaccinated within 6 versus around 18 months. A second dose of vaccine did not significantly increase immune responses.

Conclusion
One dose of mRNA vaccine should be considered sufficient to elicit a broad immune response even around 18 months after a COVID-19 diagnosis.
Red cell adenylate kinase deficiency in China: molecular study of 2 new mutations (413G > A, 223dupA)
Authors: He Sijia , Chen Hongbo , Guo Xia , Gao Ju 
Published: May 2022

AbstractBackgroundAdenylate kinase (AK) is a monomolecular enzyme widely found in a variety of organisms. It mainly catalyses the reversible transfer of adenosine nucleotide phosphate groups and plays an important role in maintaining energy metabolism. AK deficiency is a rare genetic disorder that is related to haemolytic anaemia. Chronic haemolytic anaemia associated with AK deficiency is a rare condition, and only 14 unrelated families have been reported thus far. Moreover, only 11 mutations have been identified in theAK1gene,with only 3 cases of psychomotor impairment.Case presentationThe patient was a 3-year-old boy with severe haemolytic anaemia and psychomotor retardation. A molecular study of the patient’sAKgene revealed 2 different mutations: a heterozygous missense mutation in exon 6 (c.413G > A) and a heterozygous frameshift mutation in exon 5 (c.223dupA). Molecular modelling analyses indicated that AK gene inactivation resulted in a lack of AK activity. The patient recovered after regular blood transfusion therapy.ConclusionsAK1 deficiency was diagnosed on the basis of low enzymatic activity and the identification of a mutation in theAK1gene located on chromosome 9q. Here, we report the first case of moderate red cell AK1 deficiency associated with chronic nonspherocytic haemolytic anaemia (CNSHA) in China. The genetic mutations were confirmed by Sanger sequencing. The variants were classified as pathogenic by bioinformatics tools, such as ACMG/AMP guidelines, Mutation Taster, SIFT, MACP, REVEL and PolyPhen2.2. Based on our evidence and previous literature reports, we speculate that the site of theAK1gene c.413G > A (p.Arg138His) mutation may be a high-frequency mutation site and the other mutation (c.223dupA) might be related to the neuropathogenicity caused by AK1 deficiency. NGS should be a part of newborn to early childhood screening to diagnose rare and poorly diagnosed genetic diseases as early as possible.
Progressive pulmonary fibrosis in a murine model of Hermansky-Pudlak syndrome
Authors: Abudi-Sinreich Shachar , Bodine Steven P. , Yokoyama Tadafumi , Tolman Nathanial J. , Tyrlik Michal , Testa Lauren C. , Han Chen G. , Dorward Heidi M. , Wincovitch Stephen M. , Anikster Yair , Gahl William A. , Cinar Resat , Gochuico Bernadette R. , Malicdan May Christine V. 
Published: May 2022

Abstract
Background
HPS-1 is a genetic type of Hermansky-Pudlak syndrome (HPS) with highly penetrant pulmonary fibrosis (HPSPF), a restrictive lung disease that is similar to idiopathic pulmonary fibrosis (IPF). Hps1ep/ep (pale ear) is a naturally occurring HPS-1 mouse model that exhibits high sensitivity to bleomycin-induced pulmonary fibrosis (PF). Traditional methods of administering bleomycin as an intratracheal (IT) route to induce PF in this model often lead to severe acute lung injury and high mortality rates, complicating studies focusing on pathobiological mechanisms or exploration of therapeutic options for HPSPF.

Methods
To develop a murine model of HPSPF that closely mimics the progression of human pulmonary fibrosis, we investigated the pulmonary effects of systemic delivery of bleomycin in Hps1ep/ep mice using a subcutaneous minipump and compared results to oropharyngeal delivery of bleomycin.

Results
Our study revealed that systemic delivery of bleomycin induced limited, acute inflammation that resolved. The distinct inflammatory phase preceded a slow, gradually progressive fibrogenesis that was shown to be both time-dependent and dose-dependent. The fibrosis phase exhibited characteristics that better resembles human disease with focal regions of fibrosis that were predominantly found in peribronchovascular areas and in subpleural regions; central lung areas contained relatively less fibrosis.

Conclusion
This model provides a preclinical tool that will allow researchers to study the mechanism of pulmonary fibrosis in HPS and provide a platform for the development of therapeutics to treat HPSPF. This method can be applied on studies of IPF or other monogenic disorders that lead to pulmonary fibrosis.
SRSF9 promotes colorectal cancer progression via stabilizing DSN1 mRNA in an m6A-related manner
Authors: Wang Xiaoyu , Lu Xiansheng , Wang Ping , Chen Qiaoyu , Xiong Le , Tang Minshan , Hong Chang , Lin Xiaowen , Shi Kaixi , Liang Li , Lin Jie 
Published: May 2022

Abstract
Background
Serine/arginine-rich splicing factor 9 (SRSF9) is a classical RNA-binding protein that is essential for regulating gene expression programs through its interaction with target RNA. Whether SRSF9 plays an essential role in colorectal cancer (CRC) progression and can serve as a therapeutic target is largely unknown. Here, we highlight new findings on the role of SRSF9 in CRC progression and elucidate the underlying mechanism.

Methods
CRC cell lines and clinical tissue samples were used. qRT-PCR, Western blotting, immunohistochemistry (IHC), gain- and loss-of-function assays, animal xenograft model studies, bioinformatic analysis, methylated single-stranded RNA affinity assays, gene-specific m6A quantitative qRT-PCR, dual-luciferase reporter assays and RNA stability assays were performed in this study.

Results
The expression level of SRSF9 was higher in CRC cell lines than that in an immortal human intestinal epithelial cell line. Overexpression of SRSF9 was positively associated with lymph node metastasis and Dukes stage. Functionally, SRSF9 promoted cell proliferation, migration and invasion in vitro and xenograft growth. The results of bioinformatic analysis indicated that DSN1 was the downstream target of SRSF9. In CRC cells and clinical tissue samples, the expression of SRSF9 was positively associated with the expression of DSN1. Knockdown of DSN1 partially inhibited the SRSF9-induced phenotype in CRC cells. Mechanistically, we further found that SRSF9 is an m6A-binding protein and that m6A modifications were enriched in DSN1 mRNA in CRC cells. Two m6A modification sites (chr20:36773619–36773620 and chr20:36773645–chr20:36773646) in the SRSF9-binding region (chr20:36773597–36773736) of DSN1 mRNA were identified. SRSF9 binds to DSN1 in an m6A motif- and dose-dependent manner. SRSF9 modulates the expression of DSN1 in CRC cells. Such expression regulation was largely impaired upon methyltransferase METTL3 knockdown. Moreover, knockdown of SRSF9 accelerated DSN1 mRNA turnover, while overexpression of SRSF9 stabilized DSN1 mRNA in CRC cells. Such stabilizing was also weakened upon METTL3 knockdown.

Conclusion
Overexpression of SRSF9 was associated with lymph node metastasis and Dukes stage in CRC. Knockdown of DSN1 eliminated the effects by SRSF9 overexpression in CRC. Our results indicated that SRSF9 functions as an m6A-binding protein (termed “reader”) by enhancing the stability of DSN1 mRNA in m6A-related manner. Our study is the first to report that SRSF9-mediated m6A recognition has a crucial role in CRC progression, and highlights SRSF9 as a potential therapeutic target for CRC management.
Lynch syndrome testing of colorectal cancer patients in a high-income country with universal healthcare: a retrospective study of current practice and gaps in seven australian hospitals
Authors: Steinberg Julia , Chan Priscilla , Hogden Emily , Tiernan Gabriella , Morrow April , Kang Yoon-Jung , He Emily , Venchiarutti Rebecca , Titterton Leanna , Sankey Lucien , Pearn Amy , Nichols Cassandra , McKay Skye , Hayward Anne , Egoroff Natasha , Engel Alexander , Gibbs Peter , Goodwin Annabel , Harris Marion , Kench James G , Pachter Nicholas , Parkinson Bonny , Pockney Peter , Ragunathan Abiramy , Smyth Courtney , Solomon Michael , Steffens Daniel , Toh James Wei Tatt , Wallace Marina , Canfell Karen , Gill Anthony , Macrae Finlay , Tucker Kathy , Taylor Natalie 
Published: May 2022

Abstract
Background
To inform effective genomic medicine strategies, it is important to examine current approaches and gaps in well-established applications. Lynch syndrome (LS) causes 3–5% of colorectal cancers (CRCs). While guidelines commonly recommend LS tumour testing of all CRC patients, implementation in health systems is known to be highly variable. To provide insights on the heterogeneity in practice and current bottlenecks in a high-income country with universal healthcare, we characterise the approaches and gaps in LS testing and referral in seven Australian hospitals across three states.

Methods
We obtained surgery, pathology, and genetics services data for 1,624 patients who underwent CRC resections from 01/01/2017 to 31/12/2018 in the included hospitals.

Results
Tumour testing approaches differed between hospitals, with 0–19% of patients missing mismatch repair deficiency test results (total 211/1,624 patients). Tumour tests to exclude somatic MLH1 loss were incomplete at five hospitals (42/187 patients). Of 74 patients with tumour tests completed appropriately and indicating high risk of LS, 36 (49%) were missing a record of referral to genetics services for diagnostic testing, with higher missingness for older patients (0% of patients aged ≤ 40 years, 76% of patients aged > 70 years). Of 38 patients with high-risk tumour test results and genetics services referral, diagnostic testing was carried out for 25 (89%) and identified a LS pathogenic/likely pathogenic variant for 11 patients (44% of 25; 0.7% of 1,624 patients).

Conclusions
Given the LS testing and referral gaps, further work is needed to identify strategies for successful integration of LS testing into clinical care, and provide a model for hereditary cancers and broader genomic medicine. Standardised reporting may help clinicians interpret tumour test results and initiate further actions.
Communicating with patients in the age of online portals—challenges and opportunities on the horizon for radiologists
Authors: Becker Christoph D. , Kotter Elmar 
Published: May 2022

AbstractThe deployment of electronic patient portals increasingly allows patients throughout Europe to consult and share their radiology reports and images securely and timely online. Technical solutions and rules for releasing reports and images on patient portals may differ among institutions, regions and countries, and radiologists should therefore be familiar with the criteria by which reports and images are made available to their patients. Radiologists may also be solicited by patients who wish to discuss complex or critical imaging findings directly with the imaging expert who is responsible for the diagnosis. This emphasises the importance of radiologists’ communication skills as well as appropriate and efficient communication pathways and methods including electronic tools. Radiologists may also have to think about adapting reports as their final product in order to enable both referrers and patients to understand imaging findings. Actionable reports for a medical audience require structured, organ-specific terms and quantitative information, whereas patient-friendly summaries should preferably be based on consumer health language and include explanatory multimedia support or hyperlinks. Owing to the cultural and linguistic diversity in Europe dedicated solutions will require close collaboration between radiologists, patient representatives and software developers; software tools using artificial intelligence and natural language processing could potentially be useful in this context. By engaging actively in the challenges that are associated with increased communication with their patients, radiologists will not only have the opportunity to contribute to patient-centred care, but also to enhance the clinical relevance and the visibility of their profession.
Etonogestrel contraceptive implant failure in a woman taking rifampin: a case report
Authors: Tufa Tesfaye H. , Fessehaye Abraham , Abubeker Ferid A. 
Published: May 2022

AbstractBackgroundThe etonogestrel subdermal implant is the most efficacious hormonal contraceptive currently available and provides 99.7% effective contraception. However, similar to other hormonal contraception, its effectiveness is compromised with the use of cytochrome P450 inducing drugs resulting in an unplanned pregnancy. Despite this risk, little is known about the outcome of concomitant use of rifampin and contraceptive implants.Case presentationA 24-year-old woman was provided with an etonogestrel implant in September 2018. In July 2020, she was started with rifampin based anti-tuberculosis for tuberculosis of the lymph nodes. In December 2020, she presented to the family planning clinic of St. Paul’s Hospital Millennium Medical college with a diagnosis of failed implant and second-trimester pregnancy at a gestational age of 19 weeks. The etonogestrel implant was removed and the patient was linked to antenatal care follow up.ConclusionConcomitant use of hepatic cytochrome P450 enzyme-inducing medications with certain hormonal contraceptives may reduce effectiveness resulting in unintended pregnancy. Women should be given detailed counseling about the potential for drug interactions and a multidisciplinary approach with consultation or referral to reproductive health specialists is crucial for optimal management of women who are at increased risk of contraceptive failure and unintended pregnancy.
A new automated and putatively versatile synthesis of the PSMA-ligand derivative [18F]DCFPyL using the FASTlabTM synthesizer
Authors: Hoareau Raphaël , Bach-Gansmo Tore , Cumming Paul , Olberg Dag Erlend 
Published: May 2022

Abstract
Background
Noninvasive molecular imaging using peptides and biomolecules labelled with positron emitters has become important for detection of cancer and other diseases with PET (positron emission tomography). The positron emitting radionuclide fluorine-18 is widely available in high yield from cyclotrons and has favorable decay (t1/2 109.7 min) and imaging properties. 18F-Labelling of biomolecules and peptides for use as radiotracers is customarily achieved in a two-step approach, which can be challenging to automate. 6-[18F]Fluoronicotinic acid 2,3,5,6-tetrafluorophenyl ester ([18F]F-Py-TFP) is a versatile 18F-prosthetic group for this purpose, which can be rapidly be produced in an one-step approach on solid support. This work details an automated procedure on the cassette-based GE FASTlab™ platform for the labeling of a peptidomimetic, exemplified by the case of using the Glu-CO-Lys motif to produce [18F]DCFPyL, a ligand targeting the prostate specific membrane antigen (PSMA).

Results
From fluorine-18 delivery a fully automated two-step radiosynthesis of [18F]DCFPyL was completed in 56 min with an overall end of synthesis yield as high as 37% using solid phase extraction (SPE) purification on the GE FASTlab™ platform.

Conclusions
Putatively, this radiolabeling methodology is inherently amenable to automation with a diverse set of synthesis modules, and it should generalize for production of a broad spectrum of biomolecule-based radiotracers for use in PET imaging.
Multi-drug resistant gram-negative bacterial pneumonia: etiology, risk factors, and drug resistance patterns
Authors: Assefa Muluneh 
Published: May 2022

AbstractBacterial pneumonia is one of the most serious public health issues owing to its medical and economic costs, which result in increased morbidity and mortality in people of all ages around the world. Furthermore, antimicrobial resistance has risen over time, and the advent of multi-drug resistance in GNB complicates therapy and has a detrimental impact on patient outcomes. The current review aimed to summarize bacterial pneumonia with an emphasis on gram-negative etiology, pathogenesis, risk factors, resistance mechanisms, treatment updates, and vaccine concerns to tackle the problem before it causes a serious consequence. In conclusion, the global prevalence of GNB in CAP was reported 49.7% to 83.1%, whereas in VAP patients ranged between 76.13% to 95.3%. The most commonly reported MDR-GNB causes of pneumonia wereA. baumannii, K. pneumoniae,andP. aeruginosa,withA. baumanniiisolated particularly in VAP patients and the elderly.In most studies, ampicillin, tetracyclines, amoxicillin-clavulanic acid, cephalosporins, and carbapenems were shown to be highly resistant. Prior MDR-GNB infection, older age, previous use of broad-spectrum antibiotics, high frequency of local antibiotic resistance, prolonged hospital stays, ICU admission, mechanical ventilation, and immunosuppression are associated with the MDR-GNB colonization.S. maltophiliawas reported as a severe cause of HAP/VAP in patients with mechanically ventilated and having hematologic malignancy due to its ability of biofilm formation, site adhesion in respiratory devices, and its intrinsic and acquired drug resistance mechanisms. Effective combination therapies targeting PDR strains and drug-resistant genes, antibiofilm agents, gene-based vaccinations, and pathogen-specific lymphocytes should be developed in the future.