bluuebunny/crossref_metadata_2025_split huggingface dataset:
Allele-specific silencing as therapy for familial amyotrophic lateral sclerosis caused by the p.G376D TARDBP mutation
Authors: Romano Roberta , De Luca Maria , Del Fiore Victoria Stefania , Pecoraro Martina , Lattante Serena , Sabatelli Mario , La Bella Vincenzo , Bucci Cecilia 
Published: December 2022

Abstract
Amyotrophic lateral sclerosis is a neurodegenerative disease characterized by the degeneration of motor neurons. There is no treatment for this disease that affects the ability to move, eat, speak and finally breathe, causing death. In an Italian family, a heterozygous pathogenic missense variant has been previously discovered in Exon 6 of the gene TARDBP encoding the TAR DNA-binding protein 43 protein. Here, we developed a potential therapeutic tool based on allele-specific small interfering RNAs for familial amyotrophic lateral sclerosis with the heterozygous missense mutation c.1127G&gt;A. We designed a small interfering RNA that was able to diminish specifically the expression of the exogenous Green Fluorescent Protein (TAR DNA-binding protein 43G376D mutant protein) in HEK-293T cells but not that of the Green Fluorescent Protein (TAR DNA-binding protein 43 wild-type). Similarly, this small interfering RNA silenced the mutated allele in fibroblasts derived from patients with amyotrophic lateral sclerosis but did not silence the wild-type gene in control fibroblasts. In addition, we established that silencing the mutated allele was able to strongly reduce the pathological cellular phenotypes induced by TAR DNA-binding protein 43G376D expression, such as the presence of cytoplasmic aggregates. Thus, we have identified a small interfering RNA that could be used to silence specifically the mutated allele to try a targeted therapy for patients carrying the p.G376D TAR DNA-binding protein 43 mutation.
Reactivation of schema representation in lateral occipital cortex supports successful memory encoding
Authors: Guo Dingrong , Yang Jiongjiong 
Published: December 2022

Abstract
Schemas provide a scaffold onto which we can integrate new memories. Previous research has investigated the brain activity and connectivity underlying schema-related memory formation. However, how schemas are represented and reactivated in the brain, in order to enhance memory, remains unclear. To address this issue, we used an object–location spatial schema that was learned over multiple sessions, combined with similarity analyses of neural representations, to investigate the reactivation of schema representations of object–location memories when a new object–scene association is learned. In addition, we investigated how this reactivation affects subsequent memory performance under different strengths of schemas. We found that reactivation of a schema representation in the lateral occipital cortex (LOC) during object–scene encoding affected subsequent associative memory performance only in the schema-consistent condition and increased the functional connectivity between the LOC and the parahippocampal place area. Taken together, our findings provide new insight into how schema acts as a scaffold to support the integration of novel information into existing cortical networks and suggest a neural basis for schema-induced rapid cortical learning.
A case report of Trichinella spiralis pericarditis: an unusual cause of pericardial effusion and cardiac tamponade in an immunocompetent urban black African
Authors: Nkoke Clovis , Djibrilla Siddikatou , Gobina Ronald , Dzudie Anastase 
Published: December 2022

Abstract

Background
Cardiac trichinellosis is unusual and it is associated with high mortality. We report a case of Trichinella pericarditis complicated by a large pericardial effusion and cardiac tamponade in a setting where the aetiologic diagnosis of pericardial disease is challenging.

Case summary
A 27-year-old immune-competent male patient from Cameroon consulted for pleuritic chest pain associated with fever, dry cough, and gradually worsening dyspnoea on exertion of 1-month duration. Upon admission, his blood pressure was 100/73 mmHg, the heart rate was 130/min. The clinical examination revealed a pericardial friction rub, jugular venous distension, and tender hepatomegaly. There was no lower extremity oedema. The diagnosis of pericarditis was made. A two-dimensional transthoracic echocardiogram performed showed a moderate fibrinous circumferential pericardial effusion with echocardiographic signs of tamponade. Pericardiocentesis was performed and analysis of the fluid revealed multiple, motile, roundworms which were identified as Trichinella spiralis, a nematode parasite. There was no eosinophilia on complete blood count. He was treated with Albendazole 800 mg daily per os. His clinical condition improved with resolution of the symptoms and a reduction in the size of the pericardial effusion.

Discussion
Trichinella spiralis is a rare cause of pericarditis which can be life-threatening. With the existing challenges in diagnosing the aetiology of pericardial disease in African resource-limited setting, the diagnosis can be missed leading to fatal outcomes.
Barriers to cervical cancer and breast cancer screening uptake in low- and middle-income countries: a systematic review
Authors: Srinath Ananth , van Merode Frits , Rao Shyam Vasudeva , Pavlova Milena 
Published: December 2022

AbstractThere is an alarmingly high growth in breast and cervical cancers in low- and middle-income countries. Due to late presentation to doctors, there is a lower cure rate. The screening programmes in low- and middle-income countries are not comprehensive. In this paper, we systematically analyse the barriers to screening through an accessibility framework. We performed a systematic literature search in PubMed, Mendeley and Google Scholar to retrieve all English language studies (quantitative, qualitative and mixed-methods) that contained information on breast and cervical cancer screening in low- and middle-income countries. We only considered publications published between 1 January 2016 and 31 May 2021. The review was guided by Preferred Reporting Items for Systematic Reviews and Meta-Analyses literature search extension (PRISMA-S), an extension to the PRISMA Statement for Reporting Literature Searches in Systematic Reviews. The search yielded a total of 67 articles from low- and middle-income countries in this review. We used a framework on accessibility known as the 5A framework, which distinguishes five aspects of access: approachability, acceptability, availability, affordability and appropriateness, to classify the screening barriers. We added two more aspects: awareness and angst, as they could explain other important barriers to screening. They confirmed how the lack of awareness, cost of the screening service and distance to the screening centre act as major impediments to screening. They also revealed how embarrassment and fear of screening and cultural factors such as lack of spousal or family support could be obstacles to screening. We conclude that more needs to be done by policymakers and governments to improve the confidence of the people in the health systems. Women should be made aware of the causes and risk factors of cancer through evidence-based strategies so that there is an increased adherence to screening.
History’s Toolbox in Health Professions Education: One Skill-Based Session on Social Determinants of Health
Authors: Lamb Susan 
Published: December 2022

Abstract
Aimed at clinical educators, this article reports on the use of a single skill-based session that introduces learners in Health Professions Education (HPE) to basic techniques from the discipline of history. The premise of the teaching method is a correspondence between medicine’s social determinants of health (SDH) and categories of analysis commonly used by historians. At the center are eight categories, or “tools”: social, cultural, intellectual, technological, political, economic, racial/ethnic, and gendered. Like the direct and specific implications of many diagnostic signs, each of these adjectives indicate to historians specific types of factors, or determinants. The intervention employs the demonstration-performance teaching method (explanation, demonstration, supervised practice, and evaluation). After the session, learners are able to: use “history’s toolbox” as a systematic method for evaluating socio-cultural phenomena inherent in SDH; differentiate eight types of determinants in a historical case study that represents socio-cultural complexity; recognize how categorization simultaneously enhances some determinants while obscuring others, and how the use of constructed social categories in medicine can function to help and harm patients and populations. The intervention described is rooted in scholarship and theoretical questions belonging to the discipline of history, but these are not discussed. Neither the historical content nor the teaching method described here is appropriate for research or teaching in the discipline of history.
Long-Acting Antiretroviral Drug Therapy in Adolescents: Current Status and Future Prospects
Authors: Freij Bishara J , Aldrich Aileen M , Ogrin Sara L , Olivero Rosemary M 
Published: December 2022

Abstract
Approximately 50% of human immunodeficiency virus (HIV)-infected adolescents fail to achieve complete viral suppression, largely due to nonadherence to their antiretroviral drug regimens. Numerous personal, financial, and societal barriers contribute to nonadherence, which may lead to the development of HIV drug resistance. Long-acting antiretroviral drugs hold the promise of improved adherence because they remove the need for swallowing one or more pills daily. Cabotegravir (an integrase strand transfer inhibitor) and rilpivirine (a non-nucleoside reverse transcriptase inhibitor) can now be intramuscularly co-administered to HIV-infected adolescents every 4–8 weeks if they are virologically suppressed and without resistance mutations to cabotegravir or rilpivirine. Adverse effects are few and non-severe. Widespread use of this complete antiretroviral therapy may be limited by drug costs, need for sites and skilled personnel who can administer the injections, and ethical challenges. Other long-acting medications and new antiretroviral therapy delivery systems are under active investigation and show great promise.
UK surrogates’ characteristics, experiences, and views on surrogacy law reform
Authors: Horsey Kirsty , Arian-Schad Mimi , Macklon Nicholas , Ahuja Kamal 
Published: December 2022

Abstract
What are surrogates’ views on their experience with surrogacy, their understanding of the law, and views on legal reform? We conducted an online retrospective survey of women who underwent treatment as gestational surrogates in two UK-regulated IVF centres between March 2014 and October 2021. Forty-seven surrogates responded outlining their experiences with surrogacy in the England/Wales legal context, their understandings of the law, and thoughts on potential law reform. The surrogates ranged in age, occupation, and household income. Most surrogates were white, British women. While almost half were family members or friends of the intended parents, the largest category met the intended parents through a non-profit surrogacy organization. Two-thirds of the respondents had given birth to a baby as a surrogate. Surrogates generally do not view themselves as the mother of the child that they carry and support proposals for reforms that would recognize the intended parents as legal parents from birth. More ambivalence is apparent in relation to expenses and payments, though advertising is generally supported. Draft new legislation is expected to be introduced in the UK in 2023, and the results of this study could inform public and parliamentary debates to come in the UK and elsewhere. Moreover, the results from this survey can assist the development of good practice models for care on the surrogate pathway.
The molecular gas kinematics in the host galaxy of non-repeating FRB 180924B
Authors: Hsu Tzu-Yin , Hashimoto Tetsuya , Hatsukade Bunyo , Goto Tomotsugu , Wang Po-Ya , Ling Chih-Teng , Ho Simon C-C , Uno Yuri 
Published: December 2022

ABSTRACT
Fast radio bursts (FRBs) are millisecond-duration transients with large dispersion measures. The origin of FRBs is still mysterious. One of the methods to comprehend FRB origin is to probe the physical environments of FRB host galaxies. Mapping molecular-gas kinematics in FRB host galaxies is critical because it results in star formation that is likely connected to the birth of FRB progenitors. However, most previous works of FRB host galaxies have focused on its stellar component. Therefore, we, for the first time, report the molecular gas kinematics in the host galaxy of the non-repeating FRB 180924B at z = 0.3216. Two velocity components of the CO (3 − 2) emission line are detected in its host galaxy with the Atacama Large Millimeter/submillimeter Array (ALMA): the peak of one component (−155.40 km s−1) is near the centre of the host galaxy, and another (−7.76 km s−1) is near the FRB position. The CO (3 − 2) spectrum shows asymmetric profiles with Apeak = 2.03 ± 0.39, where Apeak is the peak flux density ratio between the two velocity components. The CO (3 − 2) velocity map also indicates an asymmetric velocity gradient from −180 to 8 km s−1. These results indicate a disturbed kinetic structure of molecular gas in the host galaxy. Such disturbed kinetic structures are reported for repeating FRB host galaxies using H i emission lines in previous works. Our finding indicates that non-repeating and repeating FRBs could commonly appear in disturbed kinetic environments, suggesting a possible link between the gas kinematics and FRB progenitors.
Ordering the confusion: a study of the impact of lens models on gravitational-wave strong lensing detection capabilities
Authors: Janquart Justin , More Anupreeta , Van Den Broeck Chris 
Published: December 2022

ABSTRACT
When travelling from their source to the observer, gravitational waves can get deflected by massive objects along their travel path. For a massive lens and a good source-lens alignment, the wave undergoes strong lensing, leading to several images with the same frequency evolution. These images are separated in time, magnified, and can undergo an overall phase shift. Searches for strongly lensed gravitational waves look for events with similar masses, spins, and sky location and linked through so-called lensing parameters. However, the agreement between these quantities can also happen by chance. To reduce the overlap between background and foreground, one can include lensing models. When doing realistic searches, one does not know which model is the correct one to be used. Using an incorrect model could lead to the non-detection of genuinely lensed events. In this work, we investigate how one can reduce the false alarm probability when searching for strongly lensed events. We focus on the impact of the addition of a model for the lens density profile and investigate the effect of potential errors in the modelling. We show that the risks of false alarm are high without the addition of a lens model. We also show that slight variations in the profile of the lens model are tolerable, but a model with an incorrect assumption about the underlying lens population causes significant errors in the identification process. We also suggest some strategies to improve confidence in the detection of strongly lensed gravitational waves.
Subcutaneous injection of methotrexate: Advantages in the treatment of rheumatoid arthritis
Authors: Tanaka Yoshiya 
Published: December 2022

ABSTRACTMethotrexate (MTX) is a conventional synthetic disease-modifying antirheumatic drug, which is used in the treatment of rheumatoid arthritis. However, insufficient responses to oral MTX at lower doses as well as increased variation of drug bioavailability and a deteriorated safety profile during dose escalation are regularly observed in patients. Some of its main side effects may be overcome by temporary drug hiatus or dose reduction or can be counterbalanced with folic acid. Especially gastrointestinal side effects are a major reason for permanent treatment discontinuation. Recent data suggest that MTX in a subcutaneous injection formulation can reduce gastrointestinal effects and thus may allow us to overcome oral intolerance and improve drug survival. Here, we review the currently available literature on the efficacy and safety of subcutaneous MTX in comparison to oral MTX in the treatment of patients with rheumatoid arthritis. Despite some inconsistency between data, an improvement in the efficacy and/or safety profile of subcutaneous MTX has been demonstrated. In the USA, subcutaneous MTX is an established second-line treatment already, while in European countries this formulation is even recommended as a first-line treatment. With the recent approval of subcutaneous MTX in Japan, another beneficial treatment option is now available for Japanese patients with rheumatoid arthritis.
Making a Home of The Society for Music Theory, Inc.
Authors: Lett Stephen 
Published: December 2022

AbstractThis article studies the values animating the profession of music theory in the North American academy. Focusing on the creation and development of the field’s institutional home, the Society for Music Theory, Inc., I argue that professional music theory’s homemaking project was first built—and continues to operate—on exclusionary and assimilationist world-building practices. To conclude, I ask how we might pursue homemaking and world-building otherwise in coalition with contemporary abolitionist scholarship.
180. Impact of a two-step diagnostic bundle on hospital-onset Clostridioides difficile infection rates and treatment across a large health system.
Authors: Polisetty Radhika S , Hoff Brian M , Moore William J , Postelnick Michael , Wang Sheila K , Zembower Teresa , Chao Qi , Malczynski Michael , Barajas Grace , Silkaitis Christina , Salim Asra , Borkowski Jaime , Shah Rishita , Quinn Andrea , Johnicker Kyle , Liang Charlene , Chang Stephanie , Sutton Sarah H 
Published: December 2022

Abstract

Background
Distinguishing true Clostridioides difficile Infection (CDI) from colonization is a challenge, with nearly 20% of hospitalized adults being carriers of C. difficile. Polymerase chain reaction (PCR) testing alone is not able to distinguish colonization from infection, leading to over-diagnosis and unnecessary treatment. Despite interventions including pre-approval by antimicrobial stewardship programs (ASP), reportable hospital-onset CDI (HO-CDI) rates across our health system remained high. In 2021, we implemented a C. difficile PCR with reflex toxin enzyme immunoassay (EIA) testing strategy to improve diagnostic accuracy and treatment outcomes. The purpose of this study was to evaluate the impact of this two-step testing algorithm bundled with education, ASP support and order set changes on HO-CDI rates and C. difficile treatment across our health system.

Methods
PCR with EIA testing algorithm was implemented between May and August 2021 across seven hospitals within the Northwestern Medicine Health System. Multifaceted education was delivered to leadership and clinicians in person and electronically to. ASP performed daily diagnostic prospective audit and management support. Clinical decision support (CDS) was incorporated into order sets to promote diagnostic stewardship (Table 1, Figure 1). Standardization of analyst-developed tracking reports allowed for longitudinal monitoring across the system and at each facility, including unit- and patient-level data. Figure 1C. Difficile Testing Algorithm PCR/Reflex Toxin EIA

Results
The HO-CDI standardized infection ratio (SIR) reduced significantly from 0.8 to 0.57 p&lt; 0.001), and reportable HO-CDI cases reduced by 238 cases across the health system between May 2021 and March 2022. 6043 samples were tested, of which 282 (4.7%) were confirmed CDI cases (PCR+/toxin+) and 687 (11%) were non-CDI cases (PCR+/toxin-), of which 438 (67%) received CDI treatment. (Figure 2 and 3).
Figure 3 Actual versus avoided HO C. difficile cases.

Conclusion
The two-step CDI diagnostic and treatment bundle significantly reduced the SIR of HO-CDI. Although treatment of colonized patients remained high, a large number of patients safely avoided CDI treatment. Testing and education bundles can help advance antimicrobial and diagnostic stewardship by improving detection, treatment, and tracking of CDI.

Disclosures
Asra Salim, MPH, CPH, FAPIC, IRhythym Technologies Inc: Stocks/Bonds.
The Presence of Hemoglobin in Cervicovaginal Lavage Is Not Associated With Genital Schistosomiasis in Zambian Women From the BILHIV Study
Authors: Sturt Amy S , Webb Emily L , Phiri Comfort R , Mapani Joyce , Mudenda Maina , Himschoot Lisa , Kjetland Eyrun F , Mweene Tobias , Levecke Bruno , van Dam Govert J , Corstjens Paul L A M , Ayles Helen , Hayes Richard J , Francis Suzanna C , van Lieshout Lisette , Cools Piet , Hansingo Isaiah , Bustinduy Amaya L 
Published: December 2022

Abstract

Background
Female genital schistosomiasis (FGS) occurs when Schistosoma haematobium eggs are deposited in reproductive tissue. Female genital schistosomiasis in the cervical mucosa is associated with increased vascularity. If FGS is associated with the presence of hemoglobin in cervicovaginal lavage (CVL), the use of urinary reagent strips to detect hemoglobin in CVL could supplement FGS diagnosis.

Methods
Nonmenstruating, nonpregnant, sexually active women aged 18–31 participating in the HPTN 071 (PopART) Population-Cohort were invited in 2 Zambian communities. Genital self-swabs and a urine specimen were collected at a home visit, and CVL and hand-held colposcopy were performed at a midwife led clinic visit. Urinary reagent strips were used to identify hemoglobin in CVL. Eggs and circulating anodic antigen (CAA) were detected from urine. Visual-FGS was defined as the presence of sandy patches, rubbery papules, or abnormal blood vessels. Polymerase chain reaction (PCR)-FGS was defined as Schistosoma deoxyribonucleic acid detected by real-time PCR on CVL or cervical or vaginal swab.

Results
Of 209 women with home genital swabs and companion CVL specimens, 66% (138 of 209) had detectable CVL hemoglobin, 13.4% (28 of 209) had PCR-defined FGS, and 17.2% (36 of 209) had visual-FGS. Active Schistosoma infection, diagnosed by CAA or urine microscopy, was present in 21.0% (44 of 209) participants. Active Schistosoma infection (P = .4), PCR-FGS (P = 0.7), and visual-FGS (P = 0.3) were not associated with CVL hemoglobin presence. Results did not differ in subgroups with high infection burden (cycle threshold &lt; 35 or 2–3 positive genital PCR).

Conclusions
Polymerase chain reaction-FGS, visual-FGS, and active Schistosoma infection were not associated with the presence of CVL hemoglobin. Further research is needed to establish accessible community-based FGS diagnostics.
Comparing Prospective Incident Severe Acute Respiratory Syndrome Coronavirus 2 Infection Rates During Successive Waves of Delta and Omicron in Johannesburg, South Africa
Authors: Sokhela Simiso , Bosch Bronwyn , Hill Andrew , Simmons Bryony , Woods Joana , Johnstone Hilary , Madhi Shabir , Qavi Ambar , Ellis Leah , Akpomiemie Godspower , Bhaskar Esther , Levi Jacob , Falconer Jonathan , Mirchandani Manya , Perez Casas Carmen , Moller Karlien , Pilkington Victoria , Pepperrell Toby , Venter Willem Daniel Francois 
Published: December 2022

Abstract
In high-risk individuals in Johannesburg, during the Delta coronavirus disease 2019 wave, 22% (125/561) were positive, with 33% symptomatic (2 hospitalizations; 1 death). During Omicron, 56% (232/411) were infected, with 24% symptomatic (no hospitalizations or deaths). The remarkable speed of infection of Omicron over Delta poses challenges to conventional severe acute respiratory syndrome coronavirus 2 control measures.