bluuebunny/crossref_metadata_2025 huggingface dataset:
Complicity of States in Partnered Drone Operations
Authors: Branca Eleonora
Published: February 2022

Military operations carried out with armed drones call into question not only the international responsibility of the drone-sending State but also the potential international responsibility for complicity of assisting States. Drone strikes are conducted through a complex set of tasks that would not be possible without the military cooperation of partner States. Three main scenarios of partnered drone operations are described, namely lending foreign military bases, providing logistical and technological support and intelligence sharing for targeting purposes. The article explores the issue of State complicity under the lens of Article 16 of the Articles on the Responsibility of States for Internationally Wrongful Acts. The core features of State complicity—the ‘significant contribution element', the ‘mental element' and the ‘opposability element'—are discussed and applied to the three scenarios. The practice of partnered drone operations is extensively analysed, focusing on the assistance provided by Italy, Germany and the Netherlands to the US drone programme. The study concludes that in the cases under consideration, the international responsibility for complicity of assisting States is likely to be entailed, should the action of the assisted State result in an internationally wrongful act.
Implementation of geriatric assessment and long-term care insurance system by medical professionals in cancer treatment: a nationwide survey in Japan
Authors: Yoshida Yoichiro , Tamura Kazuo ,   the Geriatric Oncology Guideline-establishing Study Group
Published: February 2022

Background

A questionnaire survey was conducted to assess the implementation status of geriatric assessment in cancer treatment and the potential for collaboration between medical care and the long-term care insurance system.

Methods

Questionnaires were sent to 795 facilities in Japan. The questions were instructed to be answered via an online survey (SurveyMonkey®), which began in September 2020 and closed on 31 October 2020. The questionnaire consisted of 8 questions on the status of geriatric assessment implementation and 15 questions on the long-term care insurance system.

Results

In total, 631 departments in 340 (42.8%) of 795 hospitals and clinics provided responses. Approximately 81.5% of the departments did not perform geriatric assessment. The common reasons were lack of knowledge about geriatric assessment (54.0%) and lack of personnel (35.5%). Even if geriatric assessment was conducted, 63.6% of departments did not utilize geriatric assessment results in clinical practice. Approximately 61.7% of respondents were familiar with the long-term care insurance system and 62.9% with the certification process. Moreover, 28% of respondents used certification examination results in treatment planning.

Conclusions

Geriatric assessment is less recognized than the long-term care insurance system, and its results are rarely used in clinical practice. However, 28% of certification examination results are utilized in treatment decision-making. Notably, this survey first showed the incorporation of the long-term care insurance system into the medical care of vulnerable elderly patients with cancer.
Laparoscopic reduction of intersigmoid hernia: early surgical intervention for a rare form of internal hernia
Authors: Youn Sang Il , Kim Dong-Wook , Jee Ye Seob
Published: February 2022

Intersigmoid hernia is a rare form of internal hernia presenting with symptoms of bowel obstruction. A 32-year-old male visited the emergency department with chief complaint of abrupt onset of abdominal pain without any history of prior abdominal surgery. The initial abdominal X-ray and computed tomography (CT) scan exhibited mild distension of small bowel and paralytic ileus with no definitive obstruction site. However, a 12-h follow-up abdominal X-ray showed manifestations of newly appeared step-ladder sign and the CT scan displayed mechanical obstruction in the left lower quadrant area. Upon laparoscopic examination, herniation of small bowel was observed through the intersigmoid recess. Reduction was performed for about 5 cm of incarcerated ileum, and there was no sign of necrosis or lasting damage. The patient was discharged without complications. Laparoscopic management of intersigmoid hernia is possible with early surgical management of mechanical obstruction.
Contributions of sugar transporters to crop yield and fruit quality
Authors: Wen Suying , Neuhaus H Ekkehard , Cheng Jintao , Bie Zhilong
Published: February 2022

The flux, distribution, and storage of soluble sugars regulate crop yield in terms of starch, oil, protein, and total carbohydrates, and affect the quality of many horticultural products. Sugar transporters contribute to phloem loading and unloading. The mechanisms of phloem loading have been studied in detail, but the complex and diverse mechanisms of phloem unloading and sugar storage in sink organs are less explored. Unloading and subsequent transport mechanisms for carbohydrates vary in different sink organs. Analyzing the transport and storage mechanisms of carbohydrates in important storage organs, such as cereal seeds, fruits, or stems of sugarcane, will provide information for genetic improvements to increase crop yield and fruit quality. This review discusses current research progress on sugar transporters involved in carbohydrate unloading and storage in sink organs. The roles of sugar transporters in crop yield and the accumulation of sugars are also discussed to highlight their contribution to efficient breeding.
Value of Thyroid Peroxidase Antibodies in Neuroimmune Diseases: Analysis of Interference During Treatment with Intravenous Immunoglobulins
Authors: Jiménez-Legido María , Cantarín-Extremera Verónica , López-Guio María Eugenia , González-Cervera Rosa María , Martín-Prado Silvia , Sebastián-Pérez Elena , González-Gutiérrez-Solana Luis
Published: February 2022

Objective

The absence of specific markers can make the diagnosis of neuroimmune disorders difficult, making other biomarkers such as thyroid peroxidase antibodies (TPO-Abs) more relevant. Laboratory tests are susceptible to interference, especially those tests performed using immunoassay techniques. The effect of treatment with human intravenous immunoglobulin (IVIG) on the results of TPO-Abs assays has not been previously characterized.

Materials and Methods

We analyzed TPO-Abs levels in 170 children monitored in the neuroimmune disease department of a tertiary hospital. We analyzed the characteristics of patients with increased TPO-Abs values and compared their progress with and without treatment.

Results

We found that 97% of patients with elevated TPO-Abs had received IVIG. After withdrawal from IVIG, a mean TPO-Abs decrease of 62.5% at 1 month was observed. The IVIG drug preparation was found to contain 1176 U/mL of TPO-Abs. An interferogram confirmed interference.

Conclusion

It is advisable to measure levels of TPO-Abs before starting immunotherapy and remain vigilant regarding possible interference in the event of unsubstantiated elevations of this analyte.
Estimating the local dark matter density in a non-axisymmetric wobbling disc
Authors: Sivertsson S , Read J I , Silverwood H , de Salas P F , Malhan K , Widmark A , Laporte C F P , Garbari S , Freese K
Published: February 2022

The density of dark matter near the Sun, ρDM, ⊙, is important for experiments hunting for dark matter particles in the laboratory, and for constraining the local shape of the Milky Way’s dark matter halo. Estimates to date have typically assumed that the Milky Way’s stellar disc is axisymmetric and in a steady-state. Yet the Milky Way disc is neither, exhibiting prominent spiral arms and a bar, and vertical and radial oscillations. We assess the impact of these assumptions on determinations of ρDM, ⊙ by applying a free-form, steady-state, Jeans method to two different N-body simulations of Milky Way-like galaxies. In one, the galaxy has experienced an ancient major merger, similar to the hypothesized Gaia–Sausage–Enceladus; in the other, the galaxy is perturbed more recently by the repeated passage and slow merger of a Sagittarius-like dwarf galaxy. We assess the impact of each of the terms in the Jeans–Poisson equations on our ability to correctly extract ρDM, ⊙ from the simulated data. We find that common approximations employed in the literature – axisymmetry and a locally flat rotation curve – can lead to significant systematic errors of up to a factor ∼1.5 in the recovered surface mass density ∼2 kpc above the disc plane, implying a fractional error on ρDM, ⊙ of the order of unity. However, once we add in the tilt term and the rotation curve term in our models, we obtain an unbiased estimate of ρDM, ⊙, consistent with the true value within our 95 per cent confidence intervals for realistic 20 per cent uncertainties on the baryonic surface density of the disc. Other terms – the axial tilt, 2nd Poisson and time-dependent terms – contribute less than 10 per cent to ρDM, ⊙ (given current data) and can be safely neglected for now. In the future, as more data become available, these terms will need to be included in the analysis.
Superdiffusion of cosmic rays in compressible magnetized turbulence
Authors: Hu Yue , Lazarian A , Xu Siyao
Published: February 2022

Owing to the complexity of turbulent magnetic fields, modelling the diffusion of cosmic rays is challenging. Based on the current understanding of anisotropic magnetohydrodynamic (MHD) turbulence, we use test particles to examine the cosmic rays’ superdiffusion in the direction perpendicular to the mean magnetic field. By changing Alfvén Mach number MA and sonic Mach number MS of compressible MHD simulations, our study covers a wide range of astrophysical conditions including subsonic warm gas phase and supersonic cold molecular gas. We show that freely streaming cosmic rays’ perpendicular displacement increases as 3/2 to the power of the time travelled along local magnetic field lines. This power-law index changes to 3/4 if the parallel propagation is diffusive. We find that the cosmic rays’ parallel mean free path decreases in a power-law relation of $M_\mathrm{ A}^{-2}$ in supersonic turbulence. We investigate the energy fraction of slow, fast, and Alfvénic modes and confirm the dominance of Alfvénic modes in the perpendicular superdiffusion. In particular, the energy fraction of fast mode, which is the main agent for pitch-angle scattering, increases with MA, but is insensitive to MS ≥ 2. Accordingly, our results suggest that the suppressed diffusion in supersonic molecular clouds arises primarily due to the variations of MA instead of MS.
The Carbon Footprint of Bioinformatics
Authors: Grealey Jason , Lannelongue Loïc , Saw Woei-Yuh , Marten Jonathan , Méric Guillaume , Ruiz-Carmona Sergio , Inouye Michael
Published: February 2022

Bioinformatic research relies on large-scale computational infrastructures which have a nonzero carbon footprint but so far, no study has quantified the environmental costs of bioinformatic tools and commonly run analyses. In this work, we estimate the carbon footprint of bioinformatics (in kilograms of CO2 equivalent units, kgCO2e) using the freely available Green Algorithms calculator (www.green-algorithms.org, last accessed 2022). We assessed 1) bioinformatic approaches in genome-wide association studies (GWAS), RNA sequencing, genome assembly, metagenomics, phylogenetics, and molecular simulations, as well as 2) computation strategies, such as parallelization, CPU (central processing unit) versus GPU (graphics processing unit), cloud versus local computing infrastructure, and geography. In particular, we found that biobank-scale GWAS emitted substantial kgCO2e and simple software upgrades could make it greener, for example, upgrading from BOLT-LMM v1 to v2.3 reduced carbon footprint by 73%. Moreover, switching from the average data center to a more efficient one can reduce carbon footprint by approximately 34%. Memory over-allocation can also be a substantial contributor to an algorithm’s greenhouse gas emissions. The use of faster processors or greater parallelization reduces running time but can lead to greater carbon footprint. Finally, we provide guidance on how researchers can reduce power consumption and minimize kgCO2e. Overall, this work elucidates the carbon footprint of common analyses in bioinformatics and provides solutions which empower a move toward greener research.
Comparative Genomics Elucidates the Origin of a Supergene Controlling Floral Heteromorphism
Authors: Potente Giacomo , Léveillé-Bourret Étienne , Yousefi Narjes , Choudhury Rimjhim Roy , Keller Barbara , Diop Seydina Issa , Duijsings Daniël , Pirovano Walter , Lenhard Michael , Szövényi Péter , Conti Elena
Published: February 2022

Supergenes are nonrecombining genomic regions ensuring the coinheritance of multiple, coadapted genes. Despite the importance of supergenes in adaptation, little is known on how they originate. A classic example of supergene is the S locus controlling heterostyly, a floral heteromorphism occurring in 28 angiosperm families. In Primula, heterostyly is characterized by the cooccurrence of two complementary, self-incompatible floral morphs and is controlled by five genes clustered in the hemizygous, ca. 300-kb S locus. Here, we present the first chromosome-scale genome assembly of any heterostylous species, that of Primula veris (cowslip). By leveraging the high contiguity of the P. veris assembly and comparative genomic analyses, we demonstrated that the S-locus evolved via multiple, asynchronous gene duplications and independent gene translocations. Furthermore, we discovered a new whole-genome duplication in Ericales that is specific to the Primula lineage. We also propose a mechanism for the origin of S-locus hemizygosity via nonhomologous recombination involving the newly discovered two pairs of CFB genes flanking the S locus. Finally, we detected only weak signatures of degeneration in the S locus, as predicted for hemizygous supergenes. The present study provides a useful resource for future research addressing key questions on the evolution of supergenes in general and the S locus in particular: How do supergenes arise? What is the role of genome architecture in the evolution of complex adaptations? Is the molecular architecture of heterostyly supergenes across angiosperms similar to that of Primula?
The BlueScreen HC assay to predict the genotoxic potential of fragrance materials
Authors: Thakkar Yax , Joshi Kaushal , Hickey Christina , Wahler Joseph , Wall Brian , Etter Sylvain , Smith Benjamin , Griem Peter , Tate Matthew , Jones Frank , Oudraogo Gladys , Pfuhler Stefan , Choi Christopher , Williams Gary , Greim Helmut , Eisenbrand Gerhard , Dekant Wolfgang , Api Anne Marie
Published: February 2022

BlueScreen HC is a mammalian cell-based assay for measuring the genotoxicity and cytotoxicity of chemical compounds and mixtures. The BlueScreen HC assay has been utilized at the Research Institute for Fragrance Materials in a safety assessment program as a screening tool to prioritize fragrance materials for higher-tier testing, as supporting evidence when using a read-across approach, and as evidence to adjust the threshold of toxicological concern. Predictive values for the BlueScreen HC assay were evaluated based on the ability of the assay to predict the outcome of in vitro and in vivo mutagenicity and chromosomal damage genotoxicity assays. A set of 371 fragrance materials was assessed in the BlueScreen HC assay along with existing or newly generated in vitro and in vivo genotoxicity data. Based on a weight-of-evidence approach, the majority of materials in the data set were deemed negative and concluded not to have the potential to be genotoxic, while only a small proportion of materials were determined to show genotoxic effects in these assays. Analysis of the data set showed a combination of high positive agreement but low negative agreement between BlueScreen HC results, in vitro regulatory genotoxicity assays, and higher-tier test results. The BlueScreen HC assay did not generate any false negatives, thereby providing robustness when utilizing it as a high-throughput screening tool to evaluate the large inventory of fragrance materials. From the perspective of protecting public health, it is desirable to have no or minimal false negatives, as a false-negative result may incorrectly indicate the lack of a genotoxicity hazard. However, the assay did have a high percentage of false-positive results, resulting in poor positive predictivity of the in vitro genotoxicity test battery outcome. Overall, the assay generated 100% negative predictivity and 3.9% positive predictivity. In addition to the data set of 371 fragrance materials, 30 natural complex substances were evaluated for BlueScreen HC, Ames, and in vitro micronucleus assay, and a good correlation in all three assays was observed. Overall, while a positive result may have to be further investigated, these findings suggest that the BlueScreen HC assay can be a valuable screening tool to detect the genotoxic potential of fragrance materials and mixtures.
Non-equilibrium structural dynamics of supercoiled DNA plasmids exhibits asymmetrical relaxation
Authors: Shaheen Cynthia , Hastie Cameron , Metera Kimberly , Scott Shane , Zhang Zhi , Chen Sitong , Gu Gracia , Weber Lisa , Munsky Brian , Kouzine Fedor , Levens David , Benham Craig , Leslie Sabrina
Published: February 2022

Many cellular processes occur out of equilibrium. This includes site-specific unwinding in supercoiled DNA, which may play an important role in gene regulation. Here, we use the Convex Lens-induced Confinement (CLiC) single-molecule microscopy platform to study these processes with high-throughput and without artificial constraints on molecular structures or interactions. We use two model DNA plasmid systems, pFLIP-FUSE and pUC19, to study the dynamics of supercoiling-induced secondary structural transitions after perturbations away from equilibrium. We find that structural transitions can be slow, leading to long-lived structural states whose kinetics depend on the duration and direction of perturbation. Our findings highlight the importance of out-of-equilibrium studies when characterizing the complex structural dynamics of DNA and understanding the mechanisms of gene regulation.
The transient Spt4-Spt5 complex as an upstream regulator of non-coding RNAs during development
Authors: Owsian Dawid , Gruchota Julita , Arnaiz Olivier , Nowak Jacek K
Published: February 2022

The Spt4-Spt5 complex is conserved and essential RNA polymerase elongation factor. To investigate the role of the Spt4-Spt5 complex in non-coding transcription during development, we used the unicellular model Paramecium tetraurelia. In this organism harboring both germline and somatic nuclei, massive transcription of the entire germline genome takes place during meiosis. This phenomenon starts a series of events mediated by different classes of non-coding RNAs that control developmentally programmed DNA elimination. We focused our study on Spt4, a small zinc-finger protein encoded in P. tetraurelia by two genes expressed constitutively and two genes expressed during meiosis. SPT4 genes are not essential in vegetative growth, but they are indispensable for sexual reproduction, even though genes from both expression families show functional redundancy. Silencing of the SPT4 genes resulted in the absence of double-stranded ncRNAs and reduced levels of scnRNAs – 25 nt-long sRNAs produced from these double-stranded precursors in the germline nucleus. Moreover, we observed that the presence of a germline-specific Spt4-Spt5m complex is necessary for transfer of the scnRNA-binding PIWI protein between the germline and somatic nucleus. Our study establishes that Spt4, together with Spt5m, is essential for expression of the germline genome and necessary for developmental genome rearrangements.
Parathyroid hormone and phosphate homeostasis in patients with Bartter and Gitelman syndrome: an international cross-sectional study
Authors: Verploegen Maartje F A , Vargas-Poussou Rosa , Walsh Stephen B , Alpay Harika , Amouzegar Atefeh , Ariceta Gema , Atmis Bahriye , Bacchetta Justine , Bárány Peter , Baron Stéphanie , Bayrakci Umut Selda , Belge Hendrica , Besouw Martine , Blanchard Anne , Bökenkamp Arend , Boyer Olivia , Burgmaier Kathrin , Calò Lorenzo A , Decramer Stéphane , Devuyst Olivier , van Dyck Maria , Ferraro Pietro Manuel , Fila Marc , Francisco Telma , Ghiggeri Gian Marco , Gondra Leire , Guarino Stefano , Hooman Nakysa , Hoorn Ewout J , Houillier Pascal , Kamperis Konstantinos , Kari Jameela A , Konrad Martin , Levtchenko Elena , Lucchetti Laura , Lugani Francesca , Marzuillo Pierluigi , Mohidin Barian , Neuhaus Thomas J , Osman Abdaldafae , Papizh Svetlana , Perelló Manel , Rookmaaker Maarten B , Conti Valerie Said , Santos Fernando , Sawaf Ghalia , Serdaroglu Erkin , Szczepanska Maria , Taroni Francesca , Topaloglu Rezan , Trepiccione Francesco , Vidal Enrico , Wan Elizabeth R , Weber Lutz , Yildirim Zeynep Yuruk , Yüksel Selçuk , Zlatanova Galia , Bockenhauer Detlef , Emma Francesco , Nijenhuis Tom
Published: February 2022

Background

Small cohort studies have reported high parathyroid hormone (PTH) levels in patients with Bartter syndrome and lower serum phosphate levels have anecdotally been reported in patients with Gitelman syndrome. In this cross-sectional study, we assessed PTH and phosphate homeostasis in a large cohort of patients with salt-losing tubulopathies.

Methods

Clinical and laboratory data of 589 patients with Bartter and Gitelman syndrome were provided by members of the European Rare Kidney Diseases Reference Network (ERKNet) and the European Society for Paediatric Nephrology (ESPN).

Results

A total of 285 patients with Bartter syndrome and 304 patients with Gitelman syndrome were included for analysis. Patients with Bartter syndrome type I and II had the highest median PTH level (7.5 pmol/L) and 56% had hyperparathyroidism (PTH >7.0 pmol/L). Serum calcium was slightly lower in Bartter syndrome type I and II patients with hyperparathyroidism (2.42 versus 2.49 mmol/L; P = .038) compared to those with normal PTH levels and correlated inversely with PTH (rs −0.253; P = .009). Serum phosphate and urinary phosphate excretion did not correlate with PTH. Overall, 22% of patients had low serum phosphate levels (phosphate—standard deviation score < −2), with the highest prevalence in patients with Bartter syndrome type III (32%). Serum phosphate correlated with tubular maximum reabsorption of phosphate/glomerular filtration rate (TmP/GFR) (rs 0.699; P < .001), suggesting renal phosphate wasting.

Conclusions

Hyperparathyroidism is frequent in patients with Bartter syndrome type I and II. Low serum phosphate is observed in a significant number of patients with Bartter and Gitelman syndrome and appears associated with renal phosphate wasting.
Measuring patients’ experience with renal services in the UK: development and validation of the Kidney PREM
Authors: Hawkins Janine , Wellsted David , Corps Claire , Fluck Richard , Gair Rachel , Hall Natalie , Busby Amanda , Rider Beth , Farrington Ken , Sharma Shivani , van der Veer Sabine N
Published: February 2022

Background

Patient experience is a recognized aspect of quality of care for people with chronic kidney disease (CKD), but current patient-reported experience measures (PREMs) only focus on dialysis care. We developed and validated the Kidney PREM to assess patients’ experience with renal services in secondary care for any CKD stage or treatment (transplant, haemodialysis and peritoneal dialysis).

Methods

We developed the Kidney PREM in two phases, informed by a multidisciplinary expert group to ensure face validity. We organized three national data collections (2016–8) to investigate item response profiles and to conduct exploratory and confirmatory analyses to assess internal consistency. We also explored content validity in cognitive interviews and evaluated test–retest reliability. Finally, we developed the Kidney PREM Short Form for more frequent measurement of patient experience to inform local service improvements.

Results

We analysed 32 959 responses across data collections, with the 2018 collection covering all 71 UK renal centres. The Kidney PREM final version consisted of 38 items grouped into 13 themes, all pertaining to one underlying dimension reflecting the construct of ‘patient experience’ with high internal consistency (Cronbach's α = 0.94). The Kidney PREM Short Form consisted of 15 items across the same 13 themes.

Conclusions

The Kidney PREM supports the collection of reliable information on patient experience that people with CKD consider relevant, regardless of CKD stage or treatment modality. Kidney PREM data have the potential to guide local and national initiatives to improve patients’ experiences with renal services in the UK and other countries.
Payday and Public Opinion toward Taxation
Authors: Heide-Jørgensen Tobias
Published: February 2022

If citizens pay insufficient attention to tax policies or cannot figure out how they are taxed, politicians may raise taxes more than is desired by the public, with few electoral repercussions. This scenario is central to the notion of “fiscal illusion” and is potentially problematic from a democratic point of view. In this article, I argue that payday is an opportunity for citizens to update their tax preferences. When people are paid and taxed, they are likely to think more about personal consumption relative to public consumption and be more aware of how the current tax system affects their personal finances, leading to increased tax skepticism. Studying this in Denmark, where payday falls on the same day for most people, and using a temporal regression discontinuity design, I find that support for tax cuts goes up by approximately 10 percentage points at payday. Further analyses suggest that this result is not driven by narrow economic self-interest, because the effect does not systematically vary across income groups. Rather, payday seems to mobilize ideological predispositions, as the effect is largest among rightists, for whom taxes are an especially strong political symbol. The implications for opinion formation and democratic accountability are discussed.
The Challenges of Predicting Drug-Induced QTc Prolongation in Humans
Authors: Valentin Jean-Pierre , Hoffmann Peter , Ortemann-Renon Catherine , Koerner John , Pierson Jennifer , Gintant Gary , Willard James , Garnett Christine , Skinner Matthew , Vargas Hugo M , Wisialowski Todd , Pugsley Michael K
Published: February 2022

The content of this article derives from a Health and Environmental Sciences Institute (HESI) consortium with a focus to improve cardiac safety during drug development. A detailed literature review was conducted to evaluate the concordance between nonclinical repolarization assays and the clinical thorough QT (TQT) study. Food and Drug Administration and HESI developed a joint database of nonclinical and clinical data, and a retrospective analysis of 150 anonymized drug candidates was reviewed to compare the performance of 3 standard nonclinical assays with clinical TQT study findings as well as investigate mechanism(s) potentially responsible for apparent discrepancies identified. The nonclinical assays were functional (IKr) current block (Human ether-a-go-go related gene), action potential duration, and corrected QT interval in animals (in vivo corrected QT). Although these nonclinical assays demonstrated good specificity for predicting negative clinical QT prolongation, they had relatively poor sensitivity for predicting positive clinical QT prolongation. After review, 28 discordant TQT-positive drugs were identified. This article provides an overview of direct and indirect mechanisms responsible for QT prolongation and theoretical reasons for lack of concordance between clinical TQT studies and nonclinical assays. We examine 6 specific and discordant TQT-positive drugs as case examples. These were derived from the unique HESI/Food and Drug Administration database. We would like to emphasize some reasons for discordant data including, insufficient or inadequate nonclinical data, effects of the drug on other cardiac ion channels, and indirect and/or nonelectrophysiological effects of drugs, including altered heart rate. We also outline best practices that were developed based upon our evaluation.
Therapeutic Hypothermia for Neonatal Encephalopathy in Low- and Middle-Income Countries: A Literature Review
Authors: Diggikar Shivashankar , Krishnegowda Roshani
Published: February 2022

Aims

This structured review aimed to discuss the existing literature on therapeutic hypothermia for moderate to severe neonatal encephalopathy exclusively in low- and middle-income countries (LMICs).

Methods

Medline, Embase, CINHAL and Cochrane Registry were searched for original papers with therapeutic hypothermia (TH) for treating neonatal encephalopathy in LMIC with no language restrictions. The search identified 1413 papers from 1990 to 31 August 2021.

Results

Twenty-one original papers were included after duplicates removal and full-text screening in the final review. Fourteen randomized control studies and seven non-randomized studies were discussed with various modes of cooling (servo-controlled, phase changing material, traditional methods), complications during cooling, mortality and long-term neurodevelopmental assessment. Although there is sufficient evidence in LMIC favouring cooling for the reduction in mortality and improving the neurodevelopmental outcomes, nonetheless these studies were widely heterogeneous in terms of method of cooling, tools for assessing developmental outcomes, age at assessment and variations in neuroimaging tools and reporting.

Conclusion

Therapeutic hypothermia is beneficial in LMICs with low certainty of evidence in reducing mortality and improving neurodevelopmental outcomes.
Morphological disparity in a hyperdiverse mammal clade: a new morphotype and tribe of Neotropical cricetids
Authors: Pardiñas Ulyses F J , Tinoco Nicolás , Barbière Franck , Ronez Christophe , Cañón Carola , Lessa Gisele , Koch Claudia , Brito Jorge
Published: February 2022

Rhagomys is a genus of South American cricetids composed of three living species. They occur in eastern Andean and lowland tropical forests. Since description of this genus more than a century ago, it was treated as an enigmatic form within Sigmodontinae, varyingly thought to be allied to different suprageneric groups, with several scholars highlighting their presumptive autapomorphies. However, this morphologically based controversy was resolved with the advent of molecular data, indicating a weak affiliation to Thomasomyini. Here we resume the anatomical scrutiny of Rhagomys based on new evidence. New data, including CT-scan craniodental exploration and an ICAMER molar analysis, reinforce the uniqueness of this cricetid in the subfamily. In addition, we have enlarged and reworked the genetic data, composed of mitochondrial and nuclear markers, supporting not only the monophyly of Rhagomys, but also its resolution as a distinct branch of the sigmodontine radiation. To accommodate these results, we describe a new tribe for Rhagomys. The recognized clade is the most phenotypically differentiated of the Oryzomyalia and inaugurates a new arboreal morphotype. We hypothesize that Rhagomys has a set of anatomical features used to exploit understory resources by primarily insectivorous mice.
Investigating Healthcare Provider Bias Toward Patients Who Use Drugs Using a Survey-based Implicit Association Test: Pilot Study
Authors: Dahl Rachel A. , Vakkalanka J. Priyanka , Harland Karisa K. , Radke Joshua
Published: February 2022

Objectives

Negative bias against people who use illicit drugs adversely affects the care that they receive throughout the hospital. We hypothesized that emergency providers would display stronger negative bias toward these patients due to life-threatening contexts in which they treat this population. We also hypothesized that negative implicit bias would be associated with negative explicit bias.

Methods

Faculty, nurses, and trainees at a midwestern tertiary care academic hospital were invited (June 26, 2019—September 5, 2019) to complete an online implicit association test and explicit bias survey.

Results

Mean implicit association test results did not vary across demographics (n = 79). There were significant differences in explicit bias scores between departments regarding whether patients who use drugs deserve quality healthcare access (P = 0.017). We saw no significant associations between implicit and explicit bias scores.

Conclusion

Though limited by sample size, the results indicate that emergency and obstetrics/gynecology providers display more negative explicit bias toward this patient population than other providers.
Universal Hepatitis B Antibody Screening and Vaccination in Pregnancy
Authors: Prabhu Malavika , Susich Marguerite K. , Packer Claire H. , Hersch Alyssa R. , Riley Laura E. , Caughey Aaron B.
Published: February 2022

OBJECTIVE:

To evaluate the cost effectiveness of universal screening for hepatitis B immunity and vaccination among pregnant women in the United States.

METHODS:

We designed a decision-analytic model to evaluate the outcomes, costs, and cost effectiveness associated with universal hepatitis B virus (HBV) immunity screening in pregnancy with vaccination of susceptible individuals compared with no screening. A theoretical cohort of 3.6 million women, the approximate number of annual live births in the United States, was used. Outcomes included cases of HBV, hepatocellular carcinoma, decompensated cirrhosis, liver transplant and death, in addition to cost and quality-adjusted life-years (QALYs). Model inputs were derived from the literature, and the willingness-to-pay threshold was $50,000 per QALY. Univariate sensitivity analyses and Monte Carlo simulation models were performed to evaluate the robustness of the results.

RESULTS:

In a theoretical cohort of 3.6 million women, universal HBV immunity screening and vaccination resulted in 1,702 fewer cases of HBV, seven fewer cases of decompensated cirrhosis, four fewer liver transplants, and 11 fewer deaths over the life expectancy of a woman after pregnancy. Universal screening and vaccination were found to be cost effective, with an incremental cost-effectiveness ratio of $1,890 per QALY. Sensitivity analyses demonstrated the model was robust even when the prevalence of HBV immunity was high and the annual risk of HBV acquisition low.

CONCLUSION:

Among pregnant women in the United States, universal HBV immunity screening and vaccination of susceptible persons is cost effective compared with not routinely screening and vaccinating.
Efficacy and Long-term Outcomes of Repeated Large Loop Excision of the Transformation Zone of the Cervix
Authors: van de Sande Anna J. M. , Schreuder Coen M. , van Baars Romy , Koeneman Margot M. , Gerestein Cornelis G. , Kruse Arnold-Jan , van Kemenade Folkert J. , Willemsen Sten P. , van Beekhuizen Heleen J.
Published: February 2022

OBJECTIVE:

To evaluate the efficacy and long-term outcome of repeat large loop excision of the transformation zone in women with residual or recurrent cervical intraepithelial neoplasia.

METHODS:

PALGA (the Dutch Pathology Registry), a database of deidentified cervical cytologic and histologic data, was used to examine women with cervical dysplasia who underwent two or more large loop excision of the transformation zone procedures between January 2005 and June 2015. We obtained cervical cytology and histology results. The main outcome was efficacy of repeated large loop excision of the transformation zone procedure in women with residual or recurrent cervical intraepithelial neoplasia. We also examined subsequent excisional procedures and hysterectomy.

RESULTS:

We identified 499 women who had undergone two or more large loop excision of the transformation zone procedures. After their second procedure, 60.7% of women had a normal first cervical cytologic sample. The mean duration of follow-up was 68 months (0–163 months). Additional cervical excisional procedures were performed in 33.7% of women. Overall, 1.2% of women developed cervical cancer during follow-up. Moreover, 19.0% of women eventually underwent hysterectomy.

CONCLUSION:

One third of the women who undergo two large loop excision of the transformation zone procedures require an additional excisional procedure or hysterectomy. Almost one fifth of these women eventually undergo hysterectomy.
Neutralizing Monoclonal Antibodies for Coronavirus Disease 2019 (COVID-19) in Pregnancy
Authors: Richley Michael , Rao Rashmi R. , Afshar Yalda , Mei Jenny , Mok Thalia , Vijayan Tara , Weinstein Stacy , Pham Christine U. , Madamba Jason , Shin Christina S. , Suda Deborah , Han Christina S.
Published: February 2022

OBJECTIVE:

To describe outcomes associated with monoclonal antibody use in pregnant persons with mild-to-moderate coronavirus disease 2019 (COVID-19).

METHODS:

We present a retrospective case series of pregnant patients who received anti–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibody infusions at a single center from April 1, 2021, through October 16, 2021. Pregnant patients who had a positive SARS-CoV-2 polymerase chain reaction (PCR) test result and mild-to-moderate COVID-19 symptoms were eligible for monoclonal antibody infusion. Exclusion criteria for administration included need for supplemental oxygen, hospitalization due to COVID-19, and positive SARS-CoV-2 PCR test result more than 7 days before screening. All patients received either bamlanivimab plus etesevimab or casirivimab plus imdevimab based on availability and dosing instructions of the product and emerging resistance patterns in the community.

RESULTS:

During the study period, monoclonal antibody infusions were administered to 450 individuals at our institution, of whom 15 were pregnant. Of the 15 pregnant persons receiving monoclonal antibody, six (40%) had full-vaccination status at the time of infusion. Two individuals (13%, CI 0–31%) experienced systemic reactions during the infusion, both resulting in temporary changes in the fetal heart rate tracing that recovered with maternal and intrauterine resuscitative efforts. One patient delivered after infusion for worsening maternal and fetal status; the remainder of the patients did not require admission for COVID-19.

CONCLUSION:

In this case series, pregnant persons who received anti–SARS-CoV-2 monoclonal antibody infusions had generally favorable outcomes.
Noninvasive Prediction of Congenital Cytomegalovirus Infection After Maternal Primary Infection
Authors: Rouse Dwight J. , Fette Lida M. , Hughes Brenna L. , Saade George R. , Dinsmoor Mara J. , Reddy Uma M. , Pass Robert , Allard Donna , Mallett Gail , Clifton Rebecca G. , Saccoccio Frances M. , Permar Sallie R. , Gyamfi-Bannerman Cynthia , Varner Michael W. , Goodnight William H. , Tita Alan T. N. , Costantine Maged M. , Swamy Geeta K. , Heyborne Kent D. , Chien Edward K. , Chauhan Suneet P. , El-Sayed Yasser Y. , Casey Brian M. , Parry Samuel , Simhan Hyagriv N. , Napolitano Peter G. , Macones George A. ,   for the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network
Published: February 2022

OBJECTIVE:

To develop and internally validate a noninvasive method for the prediction of congenital cytomegalovirus (CMV) infection after primary maternal CMV infection.

METHODS:

We conducted a secondary analysis of a multicenter randomized placebo-controlled trial of CMV hyperimmune globulin to prevent congenital infection. Women were eligible if they had primary CMV infection, defined as detectable plasma CMV-specific immunoglobulin (Ig)M and CMV-specific IgG with avidity less than 50% before 24 weeks of gestation or IgG seroconversion before 28 weeks, and were carrying a singleton fetus without ultrasonographic findings suggestive of CMV infection. Antibody assays were performed in a single reference laboratory. Congenital infection was defined as CMV detection in amniotic fluid, neonatal urine or saliva, or postmortem tissue. Using backward elimination, we developed logit models for prediction of congenital infection using factors known at randomization. The performance of the model was assessed using leave-one-out cross-validation (a method of internal validation).

RESULTS:

Of 399 women enrolled in the trial, 344 (86%) had informative data for this analysis. Congenital infection occurred in 68 pregnancies (20%). The best performing model included government-assisted insurance, IgM index 4.5 or higher, IgG avidity less than 32%, and whether CMV was detectable by polymerase chain reaction in maternal plasma at the time of randomization. Cross-validation showed an average area under the curve of 0.76 (95% CI 0.70–0.82), indicating moderate discriminatory ability. More parsimonious one-, two-, and three-factor models performed significantly less well than the four-factor model. Examples of prediction with the four-factor model: for a woman with government-assisted insurance, avidity less than 32%, IgM index 4.5 or higher, and detectable plasma CMV, probability of congenital infection was 0.69 (95% CI 0.53–0.82); for a woman with private insurance, avidity 32% or greater, IgM index less than 4.5, and undetectable plasma CMV, probability of infection was 0.03 (95% CI 0.02–0.07).

CONCLUSION:

We developed models to predict congenital CMV infection in the presence of primary maternal CMV infection and absence of ultrasonographic findings suggestive of congenital infection. These models may be useful for patient counseling and decision making.
Risk of Sterilization Regret and Age
Authors: Danvers Antoinette A. , Evans Thomas Andrew
Published: February 2022

OBJECTIVE:

To estimate the risk of sterilization regret based on age at the time of sterilization in a contemporary group of women.

METHODS:

We conducted a retrospective analysis of cross-sectional data from the 2015–2017 and 2017–2019 National Survey of Family Growth, Female Respondent Files, to estimate the proportion of women who experience sterilization regret. Descriptive statistics were used to describe the population and the proportion with regret. Sterilization regret was defined as someone who either underwent sterilization reversal or who definitely wanted sterilization reversal. Multivariable logistic regression models were used to assess associations with sterilization regret.

RESULTS:

A total of 1,549 women who underwent sterilization were included in the analysis; 8% were aged 21–30 years, and 92% were aged older than 30 years. Of the participants, 16.9% identified as Black, 22.0% as Hispanic, and 57.2% as White. Most (58.4%) underwent a tubal sterilization procedure between age 21 and 30 years. The cumulative proportion of regret was 10.2% (12.6% for women who underwent sterilization at age 21–30 years and 6.7% for those who underwent sterilization at older than age 30 years). After controlling for covariates including age, race, parity, educational attainment, and medical reason for sterilization, the only variable that had a statistically significant association with regret was age at the time of the interview (P<.001). As women got older, they were less likely to report sterilization regret.

CONCLUSION:

Younger women experience more sterilization regret. As women get older, sterilization regret decreases. Counseling about sterilization should reveal the unpredictability of future desire, but age alone must not be a barrier to performing sterilization.
Hearing Loss and Cognitive Function: Baseline Findings From the Brazilian Longitudinal Study of Adult Health: ELSA-Brasil
Authors: Samelli Alessandra G. , Santos Itamar S. , Deal Jennifer A. , Brunoni André R. , Padilha Fernanda Y.O.M.M. , Matas Carla G. , Moreira Renata R. , Rabelo Camila M. , Murano Emi Z. , Bensenõr Isabela J. , Lotufo Paulo A. , Suemoto Claudia K.
Published: February 2022

Objective:

Hearing loss (HL) has been associated with cognitive impairment in high-income countries. However, no study has investigated this association in low- and middle-income countries. Therefore, our aim was to investigate the association between cognitive function and HL in the Brazilian Longitudinal Study of Adult Health.

Design:

Cross-sectional analysis of Longitudinal Study of Adult Health (ELSA-Brasil) with 802 individuals (35–74 years old). Hearing was measured using pure-tone audiometry. A pure-tone average (s) of thresholds at 500, 1000, 2000, and 4000 Hz was calculated. HL was defined as a PTA above 25 dB in the better ear or either ear, as a categorical variable. Cognitive performance was measured using the Consortium to Establish a Registry for Alzheimer’s Disease word list memory test, the semantic and phonemic verbal fluency (VF) tests, and the Trail Making test version B. To investigate the association between cognitive performance and HL, we used linear regression models adjusted for sociodemographic and clinical variables.

Results:

Of the total of participants, 7.6% had HL. After adjustment for sociodemographic and health confounding variables, only VF was associated with HL; a 10 dB increase in the PTA in the better ear was associated with worse performance in the phonemic VF test (β = −0.115 [95% CI, −0.203 to −0.027], p = 0.01). We found a significant interaction between HL and age in the VF domain (p = 0.01). HL was related to poor VF performance among older adults only.

Conclusion:

In a community-dwelling sample of most middle-aged adults, objectively measured HL was associated with lower VF. These results should be evaluated with caution, given the likelihood of residual confounding and the fact that only VF showed an association with HL.
Concomitant Sepsis Diagnoses in Acute Myocardial Infarction-Cardiogenic Shock: 15-Year National Temporal Trends, Management, and Outcomes
Authors: Jentzer Jacob C. , Bhat Anusha G. , Patlolla Sri Harsha , Sinha Shashank S. , Miller P. Elliott , Lawler Patrick R. , van Diepen Sean , Khanna Ashish K. , Zhao David X. , Vallabhajosyula Saraschandra
Published: February 2022

OBJECTIVES:

Mixed cardiogenic-septic shock is common and associated with high mortality. There are limited contemporary data on concomitant sepsis in acute myocardial infarction complicated by cardiogenic shock (AMI-CS).

DESIGN:

Observational study.

SETTING:

Twenty percent stratified sample of all community hospitals (2000–2014) in the United States.

PARTICIPANTS:

Adults (> 18 yr) with AMI-CS with and without concomitant sepsis.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Outcomes of interest included inhospital mortality, development of noncardiac organ failure, complications, utilization of guideline-directed procedures, length of stay, and hospitalization costs. Over 15 years, 444,253 AMI-CS admissions were identified, of which 27,057 (6%) included sepsis. The sepsis cohort had more comorbidities and had higher rates of noncardiac multiple organ failure (92% vs 69%) (all p < 0.001). In 2014, compared with 2000, the prevalence of sepsis increased from 0.5% versus 11.5% with an adjusted odds ratio (aOR) 11.71 (95% CI, 9.7–14.0) in ST-segment elevation myocardial infarction and 24.6 (CI, 16.4–36.7) (all p < 0.001) in non-ST segment elevation myocardial infarction. The sepsis cohort received fewer cardiac interventions (coronary angiography [65% vs 68%], percutaneous coronary intervention [43% vs 48%]) and had greater use of mechanical circulatory support (48% vs 45%) and noncardiac support (invasive mechanical ventilation [65% vs 41%] and acute hemodialysis [12% vs 3%]) (p < 0.001). The sepsis cohort had higher inhospital mortality (44.3% vs 38.1%; aOR, 1.21; 95% CI, 1.18–1.25; p < 0.001), longer length of stay (14.0 d [7–24 d] vs 7.0 d [3–12 d]), greater hospitalization costs (×1,000 U.S. dollars) ($176.0 [$85–$331] vs $77.0 [$36–$147]), fewer discharges to home (22% vs 44%) and more discharges to skilled nursing facilities (51% vs 28%) (all p < 0.001).

CONCLUSIONS:

In AMI-CS, concomitant sepsis is associated with higher mortality and morbidity highlighting the need for early recognition and integrated management of mixed shock.