bluuebunny/crossref_metadata_2025 huggingface dataset:
Revisiting US Undergraduate Perceptions of Non-native English Varieties: From Millennials to Generation Z
Authors: Isbell Daniel R , Crowther Dustin
Published: September 2022

As the global importance of English and its proportion of non-native speakers have continued to grow, research on Global Englishes has prioritized non-native speakers’ changing attitudes toward non-native varieties. To investigate changes in attitudes among ‘Inner Circle’ English speakers, we conceptually replicated Lindemann’s (2005) survey of Millennial US undergraduates’ attitudes toward global English varieties with a sample of Generation Z undergraduates (n = 216). This study also sought to bridge research on attitudes toward English varieties with research on judgments of English speech by including a speech rating task featuring six speakers of different global English varieties. In comparison with Lindemann’s Millennials, Generation Z had less favorable attitudes toward their own US English and generally more positive orientations to non-native Englishes. Nonetheless, Generation Z had similar conceptions of where English is spoken well and with pleasant accents, and where English is spoken poorly and unpleasantly. Participants’ attitudes toward global English varieties were positively and modestly associated with the ratings provided to individual speakers of the same variety.
Gene flow biases population genetic inference of recombination rate
Authors: Samuk Kieran , Noor Mohamed A F
Published: September 2022

Accurate estimates of the rate of recombination are key to understanding a host of evolutionary processes as well as the evolution of the recombination rate itself. Model-based population genetic methods that infer recombination rates from patterns of linkage disequilibrium in the genome have become a popular method to estimate rates of recombination. However, these linkage disequilibrium-based methods make a variety of simplifying assumptions about the populations of interest that are often not met in natural populations. One such assumption is the absence of gene flow from other populations. Here, we use forward-time population genetic simulations of isolation-with-migration scenarios to explore how gene flow affects the accuracy of linkage disequilibrium-based estimators of recombination rate. We find that moderate levels of gene flow can result in either the overestimation or underestimation of recombination rates by up to 20–50% depending on the timing of divergence. We also find that these biases can affect the detection of interpopulation differences in recombination rate, causing both false positives and false negatives depending on the scenario. We discuss future possibilities for mitigating these biases and recommend that investigators exercise caution and confirm that their study populations meet assumptions before deploying these methods.
Drosophila FMRP controls miR-276-mediated regulation of nejire mRNA for space-filling dendrite development
Authors: Li Hui , Gavis Elizabeth R
Published: September 2022

MicroRNAs are enriched in neurons and play important roles in dendritic spine development and synaptic plasticity. MicroRNA activity is controlled by a wide range of RNA-binding proteins. FMRP, a highly conserved RNA-binding protein, has been linked to microRNA-mediated gene regulation in axonal development and dendritic spine formation. FMRP also participates in dendritic arbor morphogenesis, but whether and how microRNAs contribute to its function in this process remains to be elucidated. Here, using Drosophila larval sensory neurons, we show that a FMRP-associated microRNA, miR-276, functions in FMRP-mediated space-filling dendrite morphogenesis. Using EGFP microRNA sensors, we demonstrate that FMRP likely acts by regulating miR-276a RNA targeting rather than by modulating microRNA levels. Supporting this conclusion, miR-276a coimmunoprecipitated with FMRP and this association was dependent on the FMRP KH domains. By testing putative targets of the FMRP–miR-276a regulatory axis, we identified nejire as a FMRP-associated mRNA and, using EGFP reporters, showed that the nejire 3′ untranslated region is a target of miR-276a in vivo. Genetic analysis places nejire downstream of the FMRP–miR-276a pathway in regulating dendrite patterning. Together, our findings support a model in which FMRP facilitates miR-276a-mediated control of nejire for proper dendrite space-filling morphology and shed light on microRNA-dependent dendrite developmental pathology of fragile X syndrome.
Higher Cell-Mediated Immune Responses in Patients With Inflammatory Bowel Disease on Anti-TNF Therapy After COVID-19 Vaccination
Authors: Caldera Freddy , Farraye Francis A , Necela Brian M , Cogen Davitte , Saha Sumona , Wald Arnold , Daoud Nader D , Chun Kelly , Grimes Ian , Lutz Megan , Van Helden Sean R , Swift Melanie D , Virk Abinash , Bharucha Adil E , Patel Tushar C , Gores Gregory J , Chumsri Saranya , Hayney Mary S , Knutson Keith L
Published: September 2022

Background

Some patients with inflammatory bowel disease (IBD) on immunosuppressive therapies may have a blunted response to certain vaccines, including the messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccines. However, few studies have evaluated the cell-mediated immune response (CMIR), which is critical to host defense after COVID-19 infection. The aim of this study was to evaluate the humoral immune response and CMIR after mRNA COVID-19 vaccination in patients with IBD.

Methods

This prospective study (HERCULES [HumoRal and CellULar initial and Sustained immunogenicity in patients with IBD] study) evaluated humoral immune response and CMIR after completion of 2 doses of mRNA COVID-19 vaccines in 158 IBD patients and 20 healthy control (HC) subjects. The primary outcome was the CMIR to mRNA COVID-19 vaccines in patients with IBD. The secondary outcomes were a comparison of (1) the CMIR in patients with IBD and HC subjects, (2) CMIR and humoral immune response in all participants, and (3) correlation between CMIR and humoral immune response.

Results

The majority (89%) of patients with IBD developed a CMIR, which was not different vs HC subjects (94%) (P = .6667). There was no significant difference (P = .5488) in CMIR between immunocompetent (median 255 [interquartile range, 146-958] spike T cells per million peripheral blood mononuclear cells) and immunosuppressed patients (median 377 [interquartile range, 123-1440]). There was no correlation between humoral and cell-mediated immunity after vaccination (P = .5215). In univariable analysis, anti-tumor necrosis factor therapy was associated with a higher CMIRs (P = .02) and confirmed in a multivariable model (P = .02). No other variables were associated with CMIR.

Conclusions

Most patients with IBD achieved CMIR to a COVID-19 vaccine. Future studies are needed evaluating sustained CMIR and clinical outcomes.
Co-designing marine science beyond good intentions: support stakeholders’ empowerment in transformative pathways
Authors: Cazé Cosma , Mazé Camille , Danto Anatole , Saeedi Hanieh , Lear Dan , Suominen Saara , Ginigini Joape , Brodie Gilianne , Korovulavula Isoa , Pinto Isabel Sousa
Published: September 2022

Calls for science to innovate by including stakeholders' in the creation of marine knowledge have been rising, to create impact beyond laboratories and to contribute to the empowerment of local communities when interacting with marine and coastal ecosystems. As a transdisciplinary group of scientists working on co-designing research projects, this paper draws upon our experiences to further define the concept and seek to improve the process of co-design. We highlight the key barriers for co-design processes to contribute to increasing stakeholders' capacity to produce intended effects on marine policy. We suggest that stakeholder engagement requires overcoming the resistance to non-scientific knowledge sources and considering power asymmetries in the governance and management of the ocean. We argue that power and politics must be placed at the very heart of the production of a co-designed marine science and must be an aspect of the facilitation itself. In this paper, we aim to provide insights to navigate throughout the journey of stakeholder engagement, with the critical perspective necessary to make this process socially and environmentally effective.
Ocean acidification research for sustainability: co-designing global action on local scales
Authors: Dobson K L , Newton J A , Widdicombe S , Schoo K L , Acquafredda M P , Kitch G , Bantelman A , Lowder K , Valauri-Orton A , Soapi K , Azetsu-Scott K , Isensee K
Published: September 2022

The global threat that ocean acidification poses to marine ecosystems has been recognized by the UN 2030 Agenda under Sustainable Development Goal, Target 14.3: to reduce ocean acidification. The Global Ocean Acidification Observing Network (GOA-ON) is a collaborative international network to detect and understand the drivers of ocean acidification in estuarine-coastal-open ocean environments, the resulting impacts on marine ecosystems, and to make the information available to optimize modelling studies. The Ocean Acidification Research for Sustainability (OARS) programme, endorsed by the 2021–2030 UN Decade of Ocean Science for Sustainable Development, will build on the work of GOA-ON through its seven Decade Action Outcomes. By employing a Theory of Change framework, and with the co-design of science in mind, OARS will develop an implementation plan for each Decade Action Outcome, which will identify the stakeholders and rights-holders, as well as the tools, means, and positive consequences required for their successful delivery. The organizational structure of GOA-ON, with nine regional hubs, will benefit OARS by providing a vital connection between local and global scales. GOA-ON regional hub case-studies illustrate how activities in the past and future, informed by global and regional priorities, support capacity building and the co-design of ocean acidification science.
Efficacy and safety of intraoperative cone-beam CT-guided localization of small pulmonary nodules
Authors: Kaiho Taisuke , Suzuki Hidemi , Hata Atsushi , Ito Takamasa , Tanaka Kazuhisa , Sakairi Yuichi , Kato Hideyuki , Shiko Yuki , Kawasaki Yohei , Yoshino Ichiro
Published: September 2022

OBJECTIVES

This study aimed to evaluate the efficacy and safety of intraoperative cone-beam computed tomography-guided video-assisted thoracoscopic surgery wedge resection of impalpable small pulmonary nodules.

METHODS

This was a single-centre phase 2 trial conducted between April 2018 and March 2019. Peripheral small pulmonary nodules, defined as either ground-glass opacity-dominant (>50%) nodules measuring ≤3 cm in diameter (ground-glass opacity-dominant type) or nodules measuring ≤2 cm in diameter located deeper than the nodule diameter from the visceral pleura (deep solid type), were eligible for resection using a cone-beam computed tomography-guided thoracoscopic manner. The primary end-point was macroscopic complete resection, and secondary end-points were: nodule extraction rate, operation time, localization time, marking accuracy, microscopic complete resection and safety.

RESULTS

Twenty-two nodules, in 9 men and 11 women with a mean age of 64.3 years, were visualized and resected. The nodules were located in the right upper, middle and lower lobes in 3, 1 and 5 patients, respectively, and in the left upper and lower lobes in 5 and 8 patients, respectively. Seven nodules were ground-glass opacity-dominant types, and 15 were deep solid types. Cone-beam computed tomography could clearly image all nodules. The mean time for localization was 17.4 min. The mean operation time was 110.7 min. Macroscopic complete resection was accomplished in 21 nodules (95.5%). Microscopic complete resection was achieved in all nodules (100%). Postoperative air leakage and bleeding were observed in 1 patient (5%).

CONCLUSIONS

Cone-beam computed tomography might be a safe and useful guide for video-assisted thoracoscopic surgery wedge resection of impalpable peripheral pulmonary nodules.

Date and number of IRB approval

15 November 2017, 381.

Clinical trial registration number

UMIN 000030388.
Analysis of Six Human Milk Oligosaccharides (HMO) in Infant Formula and Adult Nutritionals by 2AB Labeling and Quantification with HILIC-FLD: First Action 2022.02
Authors: Ellingson David J , Ruosch Andrew J , Foster Kalley L , Duchniak Kaitlyn M , Laessig Ian M
Published: September 2022

Background

Human milk oligosaccharides (HMO) function as a prebiotic, enhance immune functions, and support brain development for infants when fed mother’s milk. These are added to infant formula and adult nutritionals in order provide these same benefits.

Objective

To develop and validate a method that can meet the AOAC Standard Method Performance Requirements (SMPR®) outlined by the AOAC INTERNATIONAL Stakeholder Panel for Infant Formula and Adult Nutritionals (SPIFAN) through a single-laboratory validation (SLV).

Methods

This work describes a method that can analyze six different HMOs that include 2’-fucosyllactose, 3-fucosyllactose, 3’-sialyllactose, 6’-sialyllactose, lacto-N-tetraose, and lacto-N-neotetraose. The method utilizes a derivatization procedure that labels the HMO with the fluorescent compound 2-aminobenzamide. The method was optimized to provide a non-toxic derivatization procedure, automate the removal of excess derivatization reagent, and provide a chromatographic separation that can analyze multiple HMOs in a single profile.

Results

A summary from the SLV is provided.

Conclusion

The SLV was reviewed by the AOAC SPIFAN Expert Review Panel, and determined the method met the SMPR requirements for six HMO.

Highlights

The method was granted First Action Official MethodsSM status.
Effects of high- and low-fiber diets on intestinal oxidative stress in growing-finishing pigs
Authors: Jin Shunshun , Wijerathne Charith U B , Au-Yeung Kathy K W , Lei Huaigang , Yang Chengbo , O Karmin
Published: September 2022

Feed is the most expensive facet of commercial pork production. In order to reduce feed costs, using high-fiber ingredients has become a common practice. Moderate levels of fiber can maintain intestinal physiological function and promote intestinal health. Oxidative stress is linked to impaired nutrient absorption and growth performance. This study investigated the effects of high-fiber (5.26% crude fiber) and low-fiber (2.46% crude fiber) diets on growth performance and intestinal oxidative stress parameters in growing-finishing pigs. Forty growing pigs with initial body weight (27.07 ± 1.26 kg) were randomly assigned to 2 treatment groups with 10 replicates of 2 pigs per pen. Pigs were weighed on day 35, 42, and 70. The feed intake was recorded daily to calculate growth performance parameters. On day 70, eight pigs in each treatment group were randomly selected and euthanized to obtain jejunum to measure oxidative stress status. Pigs fed a high-fiber diet were heavier than those fed a low-fiber diet on days 35, 42, and 70 (P < 0.05). During the whole feeding period, pigs fed a high-fiber diet had a higher average daily gain than those fed a low-fiber diet (P < 0.05). The low-fiber diet resulted in increased levels of malondialdehyde (P < 0.05) in the jejunum, suggesting that the low-fiber diet contributed to oxidative stress in the jejunum. The low-fiber diet also led to a significant increase in glutathione and oxidized glutathione levels (P < 0.05) in the jejunum, indicating that pigs fed a low-fiber diet needed to produce more antioxidant substances to cope with oxidative stress in the intestine. This was accompanied by a significant increase in the expression of glutathione synthesizing enzymes in the jejunum of the low-fiber group (P < 0.05). These results suggest that the high-fiber diet can improve growth performance and maintain intestinal health in growing-finishing pigs by reducing intestinal oxidative stress.
Adenoid Cystic Carcinoma of the Breast: Radiologic-Pathologic Correlation
Authors: Vijapura Charmi , Rosen Lauren , Wahab Rifat
Published: September 2022

Adenoid cystic carcinoma (ACC) is an uncommon malignancy occurring most frequently in the salivary glands. Breast ACC is rare. Pain is common at the site of ACC; otherwise, presentation is similar to other primary breast cancers. Adenoid cystic carcinomas classically lack calcifications; the imaging manifestations of ACC are otherwise highly variable, likely related to multiple pathologic growth patterns. While ACC in other regions of the body tends to be more aggressive, ACC involving the breast typically has less aggressive biologic characteristics. Classic-type breast ACC has a lower tendency to recur locally with radiation, metastasize to regional lymph nodes, and spread to other parts of the body. Perineural spread of disease can be seen but is not common. The rarer solid basaloid–type has a higher tendency for local or distant spread and recurrence. Although ACC is usually triple receptor–negative (estrogen receptor, progesterone receptor, human epidermal growth factor-2 receptor), the indolent nature of this tumor dictates its management. With classic-type ACC, the inclusion of axillary surgery has no consensus and the use of chemotherapy or hormonal therapy is rare. Axillary nodal surgery and chemotherapy are often included in management of the more aggressive solid basaloid–type. An understanding of the breast imaging, histopathology, and clinical course is key for appropriate treatment and follow-up of ACC.
White rhinos and other herbivores decrease visitations and increase vigilance in response to human vocalizations
Authors: Nhleko Zoliswa N , Shrader Adrian M , Ferreira Sam M , McCleery Robert A
Published: September 2022

Harnessing the fear animals have of humans has the potential to aid in the conservation of wildlife. Most vertebrates perceive humans as “super predators.” While predator cues are an important nonlethal management tool, the use of human cues for management has rarely been implemented or experimentally tested. Extensive poaching is threatening the persistence of white rhinos (Ceratotherium simum simum), and there is a need to deter them from areas with elevated poaching risks. To investigate the feasibility of harnessing the fear white rhinos have of humans to aid in their conservation, we conducted playback experiments at rhino middens. We broadcasted repeated human (treatment) and bird (control) vocalizations, and measured changes in visitations and antipredator responses. We found that overall rhino visitations did not change in response to controls but decreased by 46% in response to human vocalizations. This pattern appears to be driven by the response of females, who decreased their visitations by 70% in response to human vocalizations, while visitations by males remained unchanged. This difference is likely related to males defending small exclusive territories. Providing evidence that changes in female visitation rates were a function of the perceived fear of white rhinos, we found that both sexes exhibited more vigilance in response to human vocalizations (males 69.5%, females 96%) compared to controls. We also saw a 63% reduction of other herbivores at treatment sites. Our findings provide evidence that the fear of humans can be used to alter the movements and behavior of female white rhinos, critical for population recovery, as well as other large herbivores.
Acari (Parasitiformes and Acariformes) From Mexico: Analysis of Their Geographical and Host Distribution in Rodentia (Cricetidae)
Authors: Herrera-Mares Angel , Guzmán-Cornejo Carmen , García-Prieto Luis , Rebollo-Hernández Andrea , León-Paniagua Livia , Del Castillo-Martínez Laura , Montiel-Parra Griselda , Ríos-Sais Gerardo
Published: September 2022

The study of Acari associated with cricetid rodents in Mexico began at the end of the 1930s. Despite efforts to gathering the information, only listings were built, but none of these studies present an analysis of the available data. A search was made through electronic databases; in addition, some not published records contained at Collection of Laboratorio de Acarología, Facultad de Ciencias, Universidad Nacional Autónoma de México were included in the inventory. Combining the literature records and those deposited in the collection, the total number of species of Acari associated with this family of rodents is 165, distributed in two superorders, four orders, 15 families, and 57 genera. Of the 15 families registered, the richest is Trombiculidae (70 nominal species and 75 taxa), followed by Laelapidae (39 and 42, respectively), Ixodidae (13 nominal and 16 taxa), and Leewenhoekiidae (13 nominal and taxa). From the bibliographic searches, a total of 76 papers were recovered with information on the association between Acari and cricetid rodents in Mexico. The main detected approach in the literature was taxonomic (75 works) and one on detection of pathogens. From the 145 known species of cricetids recorded in Mexico, only 72 (distributed in 18 genera) have been studied and found to host Acari. The use of regionalization of Mexico in provinces allowed us to map the records of Acari associated to cricetids in the most natural approximation of their distribution. We recognize and discuss seven factors that favor the scarcity and asymmetry of acarological studies in Mexico.
Resistance of Basal Forebrain Cholinergic Neurons to TDP-43 Proteinopathy in Primary Progressive Aphasia
Authors: Dunlop Sara Rose , Ayala Ivan , Spencer Callen , Flanagan Margaret E , Mesulam Marek-Marsel , Gefen Tamar , Geula Changiz
Published: September 2022

Basal forebrain cholinergic neurons (BFCN) display accumulation of neurofibrillary tangles and degeneration in Alzheimer disease and are targets of therapeutic intervention. This study determined vulnerability of BFCN to accumulation of TDP-43 in primary progressive aphasia with TDP-43 proteinopathy (PPA-TDP). Brains from 16 PPA participants with pathologically confirmed TDP-43 proteinopathy, with available paraffin-embedded sections (Group 1), or systematically sampled frozen sections (Group 2), were studied. Immunohistochemistry was performed with an antibody against phosphorylated TDP-43. BFCN were identified by their magnocellular appearance in Nissl preparations. Presence of TDP-43 inclusions and preinclusions in BFCN was determined and quantitative analysis was performed in Group 2. In Group 1, BFCN were completely free of inclusions except for occasional dystrophic neurites. Sparse TDP-43 preinclusions with smooth or granular staining in BFCN were detected. In Group 2, extremely rare TDP-43 intranuclear inclusions were detected in 0.1% of BFCN per section, along with occasional dystrophic neurites. Although sparse, significantly more preinclusions (1.4% of BFCN) were present when compared with inclusions. No hemispheric differences were noted. Small neurons near BFCN contained more preinclusions compared with BFCN. Thus, BFCN in PPA-TDP are resistant to TDP-43 proteinopathy and degeneration, suggesting that cholinergic therapy is unlikely to be effective in this disorder.
Sentiment analysis in cross-linguistic context: How can machine translation influence sentiment classification?
Authors: Bilianos Dimitris , Mikros George
Published: September 2022

In recent years, there has been a lot of interest in cross-language sentiment classification, as the research in sentiment analysis has shifted focus from English to less resourceful languages. Cross-language sentiment classification attempts to leverage the automated machine translation (MT) capability utilizing the infrastructure of languages rich in linguistic resources, mainly English, to help build sentiment analysis systems for low-resource languages. In this study, we explore how MT influences cross-language sentiment classification. To this end, we perform three different experiments, obtaining promising results. In the first experiment, we automatically translate 4,000 positive and negative reviews from English into Greek and Italian, thus obtaining labeled sentiment datasets in these languages. Then, we train a Naive Bayes classifier and compare the performance with the source dataset. In the second experiment, the translated reviews are automatically translated back into the source language (English), aiming to compare the classification accuracy with the one obtained in the original dataset. In the final approach, the reviews are translated from the source (English) into Italian through an intermediate translation in Greek to examine whether the performance was further diminished compared with the approach of the first experiment.
Mitochondrial Genomes inPerkinsusDecode Conserved Frameshifts in All Genes
Authors: Gornik Sebastian G , Flores Victor , Reinhardt Franziska , Erber Lieselotte , Salas-Leiva Dayana E , Douvropoulou Olga , Lassadi Imen , Einarsson Elin , Mörl Mario , Git Anna , Stadler Peter F , Pain Arnab , Waller Ross F
Published: September 2022

Mitochondrial genomes of apicomplexans, dinoflagellates, and chrompodellids that collectively make up the Myzozoa, encode only three proteins (Cytochrome b [COB], Cytochrome c oxidase subunit 1 [COX1], Cytochrome c oxidase subunit 3 [COX3]), contain fragmented ribosomal RNAs, and display extensive recombination, RNA trans-splicing, and RNA-editing. The early-diverging Perkinsozoa is the final major myzozoan lineage whose mitochondrial genomes remained poorly characterized. Previous reports of Perkinsus genes indicated independent acquisition of non-canonical features, namely the occurrence of multiple frameshifts. To determine both ancestral myzozoan and novel perkinsozoan mitochondrial genome features, we sequenced and assembled mitochondrial genomes of four Perkinsus species. These data show a simple ancestral genome with the common reduced coding capacity but disposition for rearrangement. We identified 75 frameshifts across the four species that occur as distinct types and that are highly conserved in gene location. A decoding mechanism apparently employs unused codons at the frameshift sites that advance translation either +1 or +2 frames to the next used codon. The locations of frameshifts are seemingly positioned to regulate protein folding of the nascent protein as it emerges from the ribosome. The cox3 gene is distinct in containing only one frameshift and showing strong selection against residues that are otherwise frequently encoded at the frameshift positions in cox1 and cob. All genes lack cysteine codons implying a reduction to 19 amino acids in these genomes. Furthermore, mitochondrion-encoded rRNA fragment complements are incomplete in Perkinsus spp. but some are found in the nuclear DNA suggesting import into the organelle. Perkinsus demonstrates further remarkable trajectories of organelle genome evolution including pervasive integration of frameshift translation into genome expression.
Biomarker associations with insomnia and secondary sleep outcomes in persons with and without HIV in the POPPY-Sleep substudy: a cohort study
Authors: Bakewell Nicholas , Sabin Caroline A , Negi Riya , Garcia-Leon Alejandro , Winston Alan , Sachikonye Memory , Doyle Nicki , Redline Susan , Mallon Patrick W G , Kunisaki Ken M
Published: September 2022

Study Objectives

We investigated associations between inflammatory profiles/clusters and sleep measures in people living with HIV and demographically-/lifestyle-similar HIV-negative controls in the Pharmacokinetic and clinical Observations in PeoPle over fiftY (POPPY)-Sleep substudy.

Methods

Primary outcome was insomnia (Insomnia Severity Index [ISI]>15). Secondary sleep outcomes included 7-day actigraphy (e.g. mean/standard deviation of sleep duration/efficiency), overnight oximetry (e.g. oxygen desaturation index [ODI]) and patient-reported measures (Patient-Reported Outcomes Measurement Information System (PROMIS) sleep questionnaires). Participants were grouped using Principal Component Analysis of 31 biomarkers across several inflammatory pathways followed by cluster analysis. Between-cluster differences in baseline characteristics and sleep outcomes were assessed using Kruskal–Wallis/logistic regression/Chi-squared/Fisher’s exact tests.

Results

Of the 465 participants included (74% people with HIV, median [interquartile range] age 54 [50–60] years), only 18% had insomnia and secondary sleep outcomes suggested generally good sleep (e.g. ODI 3.1/hr [1.5–6.4]). Three clusters with distinct inflammatory profiles were identified: “gut/immune activation” (n = 47), “neurovascular” (n = 209), and “reference” (relatively lower inflammation; n = 209). The “neurovascular” cluster included higher proportions of people with HIV, obesity (BMI>30 kg/m2), and previous cardiovascular disease, mental health disorder, and arthritis of knee/hip relative to the other two clusters. No clinically relevant between-cluster differences were observed in proportions with insomnia (17%, 18%, 20%) before (p = .76) or after (p = .75) adjustment for potential confounders. Few associations were observed among actigraphy, oximetry, and PROMIS measures.

Conclusions

Although associations could exist with other sleep measures or biomarker types not assessed, our findings do not support a strong association between sleep and inflammation in people with HIV.
Treatment with Amniotic Fluid Stem Cell Extracellular Vesicles Promotes Fetal Lung Branching and Cell Differentiation at Canalicular and Saccular Stages in Experimental Pulmonary Hypoplasia Secondary to Congenital Diaphragmatic Hernia
Authors: Khalaj Kasra , Figueira Rebeca Lopes , Antounians Lina , Gandhi Sree , Wales Matthew , Montalva Louise , Biouss George , Zani Augusto
Published: September 2022

Pulmonary hypoplasia secondary to congenital diaphragmatic hernia (CDH) is characterized by impaired branching morphogenesis and differentiation. We have previously demonstrated that administration of extracellular vesicles derived from rat amniotic fluid stem cells (AFSC-EVs) rescues development of hypoplastic lungs at the pseudoglandular and alveolar stages in rodent models of CDH. Herein, we tested whether AFSC-EVs exert their regenerative effects at the canalicular and saccular stages, as these are translationally relevant for clinical intervention. To induce fetal pulmonary hypoplasia, we gavaged rat dams with nitrofen at embryonic day 9.5 and demonstrated that nitrofen-exposed lungs had impaired branching morphogenesis, dysregulated signaling pathways relevant to lung development (FGF10/FGFR2, ROBO/SLIT, Ephrin, Neuropilin 1, β-catenin) and impaired epithelial and mesenchymal cell marker expression at both stages. AFSC-EVs administered to nitrofen-exposed lung explants rescued airspace density and increased the expression levels of key factors responsible for branching morphogenesis. Moreover, AFSC-EVs rescued the expression of alveolar type 1 and 2 cell markers at both canalicular and saccular stages and restored markers of club, ciliated epithelial, and pulmonary neuroendocrine cells at the saccular stage. AFSC-EV-treated lungs also had restored markers of lipofibroblasts and PDGFRA+ cells to control levels at both stages. EV tracking showed uptake of AFSC-EV RNA cargo throughout the fetal lung and an mRNA-miRNA network analysis identified that several miRNAs responsible for regulating lung development processes were contained in the AFSC-EV cargo. These findings suggest that AFSC-EV-based therapies hold potential for restoring fetal lung growth and maturation in babies with pulmonary hypoplasia secondary to CDH.
The role of next-generation sequencing in acute myeloid leukemia
Authors: Llop Marta , Sargas Claudia , Barragán Eva
Published: September 2022

Purpose of review

The development of high-throughput techniques like next-generation sequencing (NGS) has unraveled the genetic profile of cancer. In this review, we discuss the role of NGS on the diagnostic, risk stratification, and follow-up of patients with acute myeloid leukemia (AML).

Recent findings

NGS has become an essential tool in clinical practice for AML management. Therefore, efforts are being made to improve its applications, automation, and turnaround time. Other high-throughput techniques, such as whole genome sequencing or RNA-sequencing, can be also used to this end. However, not all institutions may be able to implement these approaches. NGS is being investigated for measurable residual disease (MRD) assessment, especially with the development of error-correction NGS. New data analysis approaches like machine learning are being investigated in order to integrate genomic and clinical data and develop comprehensive classifications and risk scores.

NGS has proven to be a useful approach for the analysis of genomic alterations in patients with AML, which aids patient management. Current research is being directed at reducing turnaround time and simplifying processes so that these techniques can be universally integrated into clinical practice.
Durable Responses in Patients With Advanced Cholangiocarcinoma on Sequential Dual-agent Immunotherapy After Progressing on Single-agent Immunotherapy
Authors: Kaakour Dalia , Hagopian Garo , Lee Sonia , Lee Fa Chyi
Published: September 2022

Objectives:

Biliary tract tumors have a poor prognosis despite advancements in targeted therapies. More recent studies have started to investigate the use of combination immunotherapy in advanced biliary cancers. However, currently, there are no clinical trials investigating the use of dual-agent immunotherapy with ipilimumab and nivolumab as a sequential treatment after patients have progressed on single-agent immunotherapy. In this case series, we discussed 3 patients with advanced cholangiocarcinoma who have an objective response to dual-agent immunotherapy with ipilimumab and nivolumab after having disease progression on pembrolizumab and multiple other failed lines of treatment.

Materials and Methods:

A case series, including 3 patients treated at the University of California, Irvine Chao Family Comprehensive Cancer Center, was completed.

Results:

Although none of the 3 patients had microsatellite instability or high tumor-mutation burden and were not necessarily predicted to have a response to dual-agent immunotherapy, all 3 patients had an objective radiographic and/or tumor-marker response to a combination of ipilimumab and nivolumab.

Conclusions:

This case series serves as proof of the concept that sequential immunotherapy can be beneficial after progression on single-agent immunotherapy for patients with advanced cholangiocarcinoma. This study can also serve as the foundation to build further tests on the true effectiveness and ideal duration of sequential therapy with dual immunotherapy agents.
Simultaneous Contralateral Autologous Breast Augmentation during Unilateral Breast Reconstruction Utilizing Deep Inferior Epigastric Flaps
Authors: Gupta Rohun , John Jithin , Gupta Rushil , Hart Justin , DeSano Jeffrey , Sachanandani Neil S. , Chaiyasate Kongkrit
Published: September 2022

Background:

It is predicted that 281,550 new cases of invasive breast cancer and 49,290 new cases of ductal carcinoma in situ will be diagnosed this year. In this study, we will detail our experience with simultaneous contralateral autologous breast augmentation during unilateral breast reconstruction utilizing bilateral deep inferior epigastric perforator (DIEP) flaps.

Methods:

A retrospective analysis of patients who underwent simultaneous contralateral autologous breast augmentation during unilateral breast reconstruction utilizing bilateral DIEP flaps by the senior surgeons at Beaumont Health Systems, Royal Oak, was conducted. Demographic data, operative details, complications, medical comorbidities, and patient outcomes were retrospectively analyzed.

Results:

Seven patients who met the inclusion criteria were identified. One patient underwent immediate reconstruction with DIEP flaps, one patient had a history of lumpectomy and underwent delayed partial breast reconstruction, three patients had delayed unilateral DIEP breast reconstruction with contralateral breast augmentation, and two patients had previous augmentations that were revised. All patients examined in this review tolerated the procedures well and had clinically viable flaps along with superior aesthetic outcomes.

Conclusions:

This technique can be applied to various clinical conditions, including immediate breast reconstruction, delayed breast reconstruction, and salvage for failed implant-based reconstruction, leading to optimal patient outcomes and satisfaction. Unilateral breast reconstruction with simultaneous contralateral autologous breast augmentation utilizing bilateral DIEP flaps is a surgical technique that more plastic surgeons should utilize.
Predictors of Success following Microvascular Replantation Surgery of the Upper Extremity in Adult Patients
Authors: Rizzo Kayla R. , Eckhoff Michael D. , Gonzalez Gilberto A. , Diamond Shawn , Nesti Leon , Dunn John C.
Published: September 2022

Background:

The purpose of this study is to ascertain which factors are associated with successful replantation in the upper extremity. Secondarily, the purpose was to determine patient factors that differentiate those patients who undergo initial replantation versus initial amputation.

Methods:

Data gathered for this retrospective study were obtained from a custom subset of the 2015–2020 IBM Truven MarketScan Commercial and IBM Truven MarketScan Medicare Supplemental databases. Data were sorted using Current Procedural Terminology codes and International Classification of Disease, Ninth and Tenth Revision, diagnosis codes.

Results:

Increasing age was significantly associated with undergoing initial amputation compared with replantation (P < 0.001; 95% CI, 47.146–50.654). Among comorbid conditions, patients with diabetes mellitus type II (2.4% versus 24.3%; P < 0.001), hypertension (11.9% versus 28.0%; P = 0.03), end-stage renal disease (0% versus 10.5%; P = 0.03), and hypertensive chronic kidney disease (0% versus 8.7%; P = 0.04) more commonly underwent an initial amputation procedure. When evaluating the need for secondary procedure after replantation, there was no statistical significance between groups when comparing age, gender, insurance type, general comorbidities, connective tissue disorders, mental health disorders, or geographic location.

Conclusions:

In conclusion, this study demonstrates that age and the presence of comorbidities are important factors in the differentiation of which patients undergo initial reimplantation versus initial amputation. Additionally, no specific factors were identified that were associated with secondary procedures after replantation.
BCG Vaccine–associated Complications in a Large Cohort of Children With Combined Immunodeficiencies Affecting Cellular and Humoral Immunity
Authors: Al-Herz Waleed , Husain Entesar H. , Adeli Mehdi , Al Farsi Tariq , Al-Hammadi Suleiman , Al Kuwaiti Amna Ali , Al-Nesf Maryam , Al Sukaiti Nashat , Al-Tamemi Salem , Shendi Hiba
Published: September 2022

Aims:

To present the details of Bacillus Calmette-Guérin (BCG)-vaccine associated complications (VACs) in combined immunodeficiencies (CID) patients.

Methods:

Five centers participated in this retrospective study and completed a data form, which included general patients’ information, clinical and laboratory data.

Results:

Among 236 CID patients, 127 were BCG vaccinated. 41.9% of patients with family history of CID and 17.1% who were diagnosed by screening were BCG vaccinated. Twenty-three patients (18.1%) developed BCG-VACs. The median age of VACs was 6 months and the median time from vaccination to complications was 6 months. The highest rate of BCG-VACs was recorded in patients receiving the Russian BCG strain compared to the Tokyo and Danish strains. Univariate analysis of T-lymphocyte subsets showed increased odds of BCG complications in patients with CD3+, CD4+, and CD8+ counts of ≤250 cells/µL. Only CD8 + count ≤250 cells/µL had increased such odds on multivariate analysis. VACs were disseminated in 13 and localized in 10 patients. Localized complication occurred earlier after vaccination (median: 4 months) compared with disseminated ones (median: 7 months). There were no significant associations between sex, administered vaccine strain, serum immunoglobulins levels, lymphocyte subsets counts, and the chance of having either localized or disseminated BCG-related complications.

Coclusions:

Although contraindicated, many patients with CID continue to be vaccinated with BCG. Low CD8 + count is a risk factor for BCG–related complications and localized complications occurred earlier than disseminated ones. Considerations should be undertaken by health care authorities especially in countries with high incidence of CID to implement newborn screening, delay the time of BCG vaccine administration beyond 6 months of age and to use the relatively safer strains like the Danish and Tokyo ones.
Epidemiology of Exposures, Preceding Illness and Testing History in Children With Multisystem Inflammatory Syndrome in Children in the First 18 Months of the COVID-19 Pandemic, Los Angeles County, California
Authors: Newhouse Caitlin N. , Finn Lauren , Gragnani Candace M. , Hathaway Susan , Nunez Denise , Malenfant Jason , Fernandes Priyanka , Kim Moon , Terashita Dawn , Balter Sharon
Published: September 2022

We describe the epidemiology of COVID-19 exposure, preceding illness, and SARS-CoV-2 testing in a large population with MIS-C during the first 18 months of the COVID-19 pandemic. The majority of cases had exposure, preceding illness, or positive SARS-CoV-2 testing 4–8 weeks before MIS-C onset. Serology can help establish epidemiological link to COVID-19 when past infection or exposure are unknown.
Disparities in Diagnosis and Treatment of Cervical Adenocarcinoma Compared With Squamous Cell Carcinoma: An Analysis of the National Cancer Database, 2004–2017
Authors: Smith Anna Jo Bodurtha , Beavis Anna L. , Rositch Anne F. , Levinson Kimberly
Published: September 2022

Objectives

The aim of the study are to compare trends in diagnosis and treatment of adenocarcinoma of the cervix (AC) to squamous cell carcinoma of the cervix (SCC) and to examine associations between stage at diagnosis and guideline-concordant treatment with race, age, and insurance type for AC and SCC.

Materials and Methods

We performed a retrospective cohort study of cervical AC (n = 18,811) and SCC (n = 68,421) from the 2004–2017 National Cancer Database. We used generalized linear models to evaluate trends in frequency of histologies and to evaluate associations between race, age, and insurance status with stage of diagnosis and receipt of National Comprehensive Cancer Network guideline–concordant treatment for AC and SCC.

Results

The proportion of AC relative to SCC increased from 19.4% (95% CI = 18.4–20.5) to 23.2% (95% CI = 22.2–24.2) from 2004 to 2017 (p < .001). Compared with SCC, women with AC were younger, more likely to be White, and privately insured (p < .001). Older women with AC were 44% less likely to be diagnosed with early-stage disease than younger women (adjusted relative risk = 0.56, 95% CI = 0.52–0.60); there was no significant difference for SCC. Black women with AC were 16% less likely to be diagnosed with early-stage disease (adjusted relative risk [aRR] = 0.84, 95% CI = 0.79–0.89) than White women. Women with public insurance were less likely to be diagnosed at an early stage for both AC (aRR = 0.81, 95% CI = 0.78–0.84) and SCC (aRR = 0.79, 95% CI = 0.77–0.81). Rates of guideline-concordant treatment were similar for AC and SCC, with minimal differences by age, race, and insurance.

Conclusions

As the proportion of AC to SCC rises, important race and age-related disparities must be addressed to reduce unnecessary morbidity and death.
Updates in the use of cannabis for insomnia
Authors: Earl David C. , Proano Marco
Published: September 2022

Purpose of review

This review aims to summarize recent updates in the area of cannabis use for insomnia.

Recent findings

Cannabis products have continued to become more potent, particularly in regard to delta-9- tetrahydrocannabinol (THC) concentration. Additionally, the use of cannabis has continued to become more accepted with less legal restrictions. The reported use of cannabis for relief of symptoms in sleep disorders appears to be increasing, however the specific effects of cannabinoids on sleep varies with cannabinoid type and concentration. Some evidence supports claims of efficacy of cannabinoids in sleep disorders such as insomnia, while other evidence is either lacking or in some cases contradictory. Regular cannabis use has been associated with withdrawal which can profoundly alter sleep. Also, clinicians should be aware of the potential effects of cannabis on the metabolism of other medications as well as the fact that cannabis use has been reported in a significant number of women in the periods before, during, and after pregnancy.

Cannabis use has been becoming more and more prevalent in the setting of relaxed restrictions and easier consumer level access to cannabis and cannabis products. A relative paucity of high quality evidence regarding the effects of cannabis on sleep and the treatment of insomnia symptoms remains. The optimal type, concentration, ratio, and dosage form of cannabinoids in the treatment of insomnia symptoms needs further clarification. As the trend of acceptance and use of cannabis continues, more high quality evidence to help guide clinicians in their recommendations will hopefully become available.
The role of surgery for loco-regional and advanced urological cancers
Authors: Chow Kit Mun , Tay Kae Jack , Yuen John , Chen Kenneth
Published: September 2022

Purpose of review

There is a general misconception that surgery is the antithesis of palliation. However, symptom mitigation, the basic tenet of palliative interventions, can be achieved by invasive procedures. Surgical care, thus, plays an important role in palliative oncology, alongside radiation and systemic therapy. There is global movement to improve palliation in oncology, and thus it is timely to evaluate the role of surgical interventions can play in this setting.

Recent findings

Many of the surgical interventions done with palliative intent were first established as curative options. Most studies looked at interventions for local control of primary tumour including extirpative surgeries, while some studies studied pain relief for bone metastases. Results show that patients have an acceptable survival outcome and complication rate comparable to those done in the curative setting. However, not all studies report functional outcomes and symptom-relief consistently, highlighting an unmet need.

More studies are needed to further define the role of surgery in palliative care. Randomized controlled trials studying surgical intervention in the palliative setting will be challenging because of lack of equipoise, inherent bias in patient and disease characteristics in those who undergo surgery. Nonetheless, studies should endeavour to study symptom-free survival and PROMs as meaningful endpoints of interventions performed in a palliative setting rather than solely focus on hard oncological endpoints of survival.