bluuebunny/crossref_metadata_2025 huggingface dataset:
Natural Selection Shapes Maintenance of Orthologous sRNAs in Divergent Host-Restricted Bacterial Genomes
Authors: Thairu Margaret W , Meduri Venkata Rama Sravani , Degnan Patrick H , Hansen Allison K
Published: June 2021

Historically it has been difficult to study the evolution of bacterial small RNAs (sRNAs) across distantly related species. For example, identifying homologs of sRNAs is often difficult in genomes that have undergone multiple structural rearrangements. Also, some types of regulatory sRNAs evolve at rapid rates. The high degree of genomic synteny among divergent host-restricted bacterial lineages, including intracellular symbionts, is conducive to sRNA maintenance and homolog identification. In turn, symbiont genomes can provide us with novel insights into sRNA evolution. Here, we examine the sRNA expression profile of the obligate symbiont of psyllids, Carsonella ruddii, which has one of the smallest cellular genomes described. Using RNA-seq, we identified 36 and 32 antisense sRNAs (asRNAs) expressed by Carsonella from the psyllids Bactericera cockerelli (Carsonella-BC) and Diaphorina citri (Carsonella-DC), respectively. The majority of these asRNAs were associated with genes that are involved in essential amino acid biosynthetic pathways. Eleven of the asRNAs were conserved in both Carsonella lineages and the majority were maintained by selection. Notably, five of the corresponding coding sequences are also the targets of conserved asRNAs in a distantly related insect symbiont, Buchnera. We detected differential expression of two asRNAs for genes involved in arginine and leucine biosynthesis occurring between two distinct Carsonella-BC life stages. Using asRNAs identified in Carsonella, Buchnera, and Profftella which are all endosymbionts, and Escherichia coli, we determined that regions upstream of these asRNAs encode unique conserved patterns of AT/GC richness, GC skew, and sequence motifs which may be involved in asRNA regulation.
Constitutive Instrumentalism and the Fragility of Responsibility
Authors: Vargas Manuel
Published: June 2021

Constitutive instrumentalism is the view that responsibility practices arise from and are justified by our being prosocial creatures who need responsibility practices to secure specific kinds of social goods. In particular, responsibility practices shape agency in ways that disposes adherence to norms that enable goods of shared cooperative life. The mechanics of everyday responsibility practices operate, in part, via costly signaling about the suitability of agents for coordination and cooperation under conditions of shared cooperative life. So, there are a range of identifiable conditions where the ordinary operation of responsibility practices—and thus, the usual normative force of the practices—is disrupted. Even so, these conditions are not so widespread as to favor a more thoroughgoing abandonment of responsibility practices.
Wimpy Retributivism and the Promise of Moral Influence Theorists
Authors: McKenna Michael
Published: June 2021

Wimpy retributivism finds reasons to refrain from giving the blameworthy and culpable what they deserve, even if it comes to very little. These reasons have to do with the moral hazards of being mistaken about when harsh treatment is justified. A moral influence theory can help supplement retributivist reasons with further consequentialist considerations and thereby keep these skeptical worries in check.
Local states of chromatin compaction at transcription start sites control transcription levels
Authors: Ishihara Satoru , Sasagawa Yohei , Kameda Takeru , Yamashita Hayato , Umeda Mana , Kotomura Naoe , Abe Masayuki , Shimono Yohei , Nikaido Itoshi
Published: June 2021

The ‘open’ and ‘compact’ regions of chromatin are considered to be regions of active and silent transcription, respectively. However, individual genes produce transcripts at different levels, suggesting that transcription output does not depend on the simple open-compact conversion of chromatin, but on structural variations in chromatin itself, which so far have remained elusive. In this study, weakly crosslinked chromatin was subjected to sedimentation velocity centrifugation, which fractionated the chromatin according to its degree of compaction. Open chromatin remained in upper fractions, while compact chromatin sedimented to lower fractions depending on the level of nucleosome assembly. Although nucleosomes were evenly detected in all fractions, histone H1 was more highly enriched in the lower fractions. H1 was found to self-associate and crosslinked to histone H3, suggesting that H1 bound to H3 interacts with another H1 in an adjacent nucleosome to form compact chromatin. Genome-wide analyses revealed that nearly the entire genome consists of compact chromatin without differences in compaction between repeat and non-repeat sequences; however, active transcription start sites (TSSs) were rarely found in compact chromatin. Considering the inverse correlation between chromatin compaction and RNA polymerase binding at TSSs, it appears that local states of chromatin compaction determine transcription levels.
Newly established patient-derived organoid model of intracranial meningioma
Authors: Yamazaki Shintaro , Ohka Fumiharu , Hirano Masaki , Shiraki Yukihiro , Motomura Kazuya , Tanahashi Kuniaki , Tsujiuchi Takashi , Motomura Ayako , Aoki Kosuke , Shinjo Keiko , Murofushi Yoshiteru , Kitano Yotaro , Maeda Sachi , Kato Akira , Shimizu Hiroyuki , Yamaguchi Junya , Adilijiang Alimu , Wakabayashi Toshihiko , Saito Ryuta , Enomoto Atsushi , Kondo Yutaka , Natsume Atsushi
Published: June 2021

Background

Recent comprehensive studies have revealed several molecular alterations that are frequently found in meningiomas. However, effective treatment reagents targeting specific molecular alterations have not yet been identified because of the limited number of representative research models of meningiomas.

Methods

We performed organoid cultures using meningioma cells and meningioma tumor tissues. Using immunohistochemistry and molecular analyses consisting of whole-exome sequencing, RNA-seq, and DNA methylation analyses, we compared the histological findings and molecular profiling of organoid models with those of parental tumors. Further, using these organoid models together with a public database of meningiomas, we explored molecular alterations, which are a potent treatment target for meningioma.

Results

We established 18 organoid models comprising of two malignant meningioma cells (HKBMM and IOMM-Lee), 10 benign meningiomas, four malignant meningiomas, and two solitary fibrous tumors (SFTs). The organoids exhibited consistent histological features and molecular profiles with those of the parental tumors. Using a public database, we identified that upregulated forkhead box M1 (FOXM1) was correlated with increased tumor proliferation. Overexpression of FOXM1 in benign meningioma organoids increased organoid proliferation; depletion of FOXM1 in malignant organoids decreased proliferation. Additionally, thiostrepton, a FOXM1 inhibitor combined with radiation therapy, significantly inhibited the proliferation of malignant meningioma organoid models.

Conclusions

An organoid model for meningioma enabled us to elucidate the tumor biology of meningioma along with potent treatment targets for meningioma.
Tuning 2D magnetism in Fe3+XGeTe2 films by element doping
Authors: Liu Shanshan , Li Zihan , Yang Ke , Zhang Enze , Narayan Awadhesh , Zhang Xiaoqian , Zhu Jiayi , Liu Wenqing , Liao Zhiming , Kudo Masaki , Toriyama Takaaki , Yang Yunkun , Li Qiang , Ai Linfeng , Huang Ce , Sun Jiabao , Guo Xiaojiao , Bao Wenzhong , Deng Qingsong , Chen Yanhui , Yin Lifeng , Shen Jian , Han Xiaodong , Matsumura Syo , Zou Jin , Xu Yongbing , Xu Xiaodong , Wu Hua , Xiu Faxian
Published: June 2021

Two-dimensional (2D) ferromagnetic materials have been discovered with tunable magnetism and orbital-driven nodal-line features. Controlling the 2D magnetism in exfoliated nanoflakes via electric/magnetic fields enables a boosted Curie temperature (TC) or phase transitions. One of the challenges, however, is the realization of high TC 2D magnets that are tunable, robust and suitable for large scale fabrication. Here, we report molecular-beam epitaxy growth of wafer-scale Fe3+XGeTe2 films with TC above room temperature. By controlling the Fe composition in Fe3+XGeTe2, a continuously modulated TC in a broad range of 185–320 K has been achieved. This widely tunable TC is attributed to the doped interlayer Fe that provides a 40% enhancement around the optimal composition X = 2. We further fabricated magnetic tunneling junction device arrays that exhibit clear tunneling signals. Our results show an effective and reliable approach, i.e. element doping, to producing robust and tunable ferromagnetism beyond room temperature in a large-scale 2D Fe3+XGeTe2 fashion.
How are health, nutrition, and physical activity discussed in international guidelines and standards for children in care? A narrative review
Authors: Green Rachael , Bergmeier Heidi , Chung Alexandra , Skouteris Helen
Published: June 2021

Background

Children in care (CiC) have often experienced trauma and, as a result, are at high risk for poor health outcomes. It is imperative that human-service stakeholders provide trauma-informed health services and interventions. However, little is known about how health promotion is addressed in the standards and guidelines for CiC. For this scoping review, the aim was to examine and compare how nutrition and physical activity are discussed in: 1) federal standards for CiC across the United Kingdom, the United States, New Zealand, and Australia; and 2) state and territory guidance in Australia.

Method

The grey literature was searched for documents outlining key child-welfare standards, guidelines, or policies for the provision of care across foster, kinship, or residential care. Documents were examined for the inclusion of recommendations and/or strategies focused on primary health and the promotion of nutrition and/or physical activity.

Results

A total of 52 documents were included in this review: 28 outlining international federal guidance and 24 Australian documents. In the United States, New Zealand, and Australia, references to physical activity were often broad, with minimal direction, and nutrition was often neglected; the United Kingdom provided more detailed guidance to promote nutrition and physical activity among CiC.

Conclusion

There is a lack of consistency and specificity in guidelines supporting healthy lifestyle interventions for CiC both internationally and within Australia. It is recommended that 1) specific trauma-informed health promotion guidelines are developed for CiC; and 2) trauma-informed health promotion training is provided to carers. Doing so will ensure that care is provided in a manner in which stakeholders recognize the signs and consequences of trauma in order to determine the most appropriate health interventions to improve outcomes and prevent ongoing trauma for this population.
Conflict and the nature of precautionary wealth
Authors: Sinha Rishabh , Aghabarari Leila , Rostom Ahmed
Published: June 2021

This article examines the accumulation of precautionary wealth in Afghanistan using detailed data from a large household survey. A percent increase in income variance is associated with a 0.22 and 0.84% increase in broad and narrow wealth, respectively. This precautionary response is most pronounced at the extremes of wealth distribution. Wealthy households rely exclusively on livestock, while less affluent use jewelry for self-insurance. Conflict amplifies the precautionary motive, with households in high-conflict provinces reporting higher wealth at the same level of uncertainty. An increase in conflict intensity is also associated with an expansion of livestock weight in the asset portfolio.
Suboptimal Response to Coronavirus Disease 2019 Messenger RNA Vaccines in Patients With Hematologic Malignancies: A Need for Vigilance in the Postmasking Era
Authors: Agha Mounzer E , Blake Maggie , Chilleo Charles , Wells Alan , Haidar Ghady
Published: June 2021

We measured severe acute respiratory syndrome coronavirus 2 immunoglobulin G responses in 67 patients with hematological malignancies after 2 messenger RNA vaccine doses. Forty-six percent were nonresponders; patients with B-cell chronic lymphocytic leukemia were at highest risk (77% nonresponders). Patients with hematological malignancies should continue wearing masks and socially distancing. Studies of revaccination, boosters, and humoral immune correlates of protection are needed.
B-box protein BBX32 integrates light and brassinosteroid signals to inhibit cotyledon opening
Authors: Ravindran Nevedha , Ramachandran Harshil , Job Nikhil , Yadav Arpita , Vaishak K.P. , Datta Sourav
Published: June 2021

Cotyledon opening is a key morphological change that occurs in seedlings during de-etiolation. Brassinosteroids (BRs) inhibit the opening of cotyledons in darkness while light promotes cotyledon opening. The molecular regulation of the interplay between light and BR to regulate cotyledon opening is not well understood. Here, we show the B-box protein BBX32 negatively regulates light signaling and promotes BR signaling to inhibit cotyledon opening in Arabidopsis (Arabidopsis thaliana). BBX32 is highly expressed in the cotyledons of seedlings during de-etiolation. bbx32 and 35S:BBX32 seedlings exhibit enhanced and reduced cotyledon opening, respectively, in response to both light and brassinazole treatment in dark, suggesting that BBX32 mediates cotyledon opening through both light and BR signaling pathways. BBX32 expression is induced by exogenous BR and is upregulated in bzr1-1D (BRASSINAZOLE RESISTANT1-1D). Our in vitro and in vivo interaction studies suggest that BBX32 physically interacts with BZR1. Further, we found that PHYTOCHROME-INTERACTING FACTOR 3 (PIF3) interacts with BBX32 and promotes BR-mediated cotyledon closure. BBX32, BZR1, and PIF3 regulate the expression of common target genes that modulate the opening and closing of cotyledons. Our work suggests BBX32 integrates light and BR signals to regulate cotyledon opening during de-etiolation.
The latest HyPe(r) in plant H2O2 biosensing
Authors: Ugalde José Manuel , Schlößer Michelle , Dongois Armelle , Martinière Alexandre , Meyer Andreas J.
Published: June 2021

HyPer7 senses minute amounts of H2O2 independent of pH and the glutathione redox potential and enables detection of physiological H2O2 fluxes within the cytosol and between subcellular compartments.
Integral and integro-differential equations with an exponential kernel and applications
Authors: Antipov Y A , Mkhitaryan S M
Published: June 2021

A convolution integral equation of the first kind and integro-differential equation of the second kind with the kernel $e^{-\gamma |y-\eta|}$ on a finite and semi-infinite interval are analyzed. For the former equation necessary and sufficient conditions for the existence and uniqueness of the solution are obtained, and when the solution exists, a closed-form representation for the solution is derived. On the basis of these results new integral relations for the spheroidal functions and Laguerre polynomials are obtained. The integro-differential equations on a finite and semi-infinite interval are transformed into a vector and scalar Riemann–Hilbert problem, respectively. Both problems are solved in closed-form. An application of these solutions to bending problems of a strip-shaped and a half-plane-shaped plate contacting with an elastic linearly deformable three-dimensional foundation characterized by the Korenev kernel $AK_0(\delta r)$ ($A$ and $\delta$ are parameters, $K_0(\cdot)$ is the modified Bessel function, and $r=\sqrt{(x-\xi)^2+(y-\eta)^2}$) is considered.
Race and Ideology in a Pandemic: White Privilege and Patterns of Risk Perception during COVID-19
Authors: Vargas Nicholas , Mora G Cristina , Gleeson Shannon
Published: June 2021

Drawing on a unique survey dataset of Californians collected during the early stages of the COVID-19 pandemic, this article examines how race and ideology shape perceptions of risk. Specifically, we position the pandemic as an “unsettled time” (Swidler 1986) and examine how different racialized groups made sense of the economic and health risks posed during this unprecedented period. We find that even when accounting for economic precarity and potential exposure to COVID-19, as well as for various other measures of social status, racialized minorities felt significantly more threatened by COVID-19 than did whites. Religion and political ideology mediated this relationship to some degree, but the racialized differences were substantial. Indeed, we find that even the most liberal whites reported being significantly less concerned about some COVID-19 risks than the most politically conservative of our Latinx and Black respondents. By linking the literature on race and racial stratification with research on risk and culture, we argue that whiteness facilitates a cognitive insulating effect vis-à-vis COVID-19 risks. We discuss the theoretical implications of our findings and conclude by highlighting the enduring importance of racialization, including various manifestations of white privilege, when assessing the social and cultural realities of crises on the ground.
Strategic Citizenship in China: Birth Tourism and the “American Hukou”
Authors: Folse Brandon
Published: June 2021

The increasing acceptance of dual citizenship globally and the rise of new strategies to acquire “external” citizenship have led to a shift from studying citizenship in the confines of single nation-states to perceiving it as existing in a global hierarchy of “citizenship constellations.” Much of this literature, however, focuses on nations which permit dual citizenship and do not have internal citizenship hierarchies. This article adds to that literature by considering one such external citizenship acquisition method—popularly referred to as “birth tourism.” Based on 23 in-depth interviews and a textual analysis of an online social media group for returnees, I argue that Chinese families use the “external passport” (U.S. citizenship) within the logics of China’s “internal passport” hierarchy (the hukou) to create a unique “citizenship constellation.” U.S. citizenship—understood as the “American hukou”—is more valuable within China’s borders than beyond, as it helps navigate national fertility and education policies. However, maintaining U.S. citizenship in China requires extra labor for parents, particularly mothers. Yet these efforts are still worth it because the acquisition of global citizenship via birth tourism permits families to reap the benefits of global citizenship without damaging their social status, economic security, and family structures.
A genome-wide association study identifies Arabidopsis thaliana genes that contribute to differences in the outcome of infection with two Turnip mosaic potyvirus strains that differ in their evolutionary history and degree of host specialization
Authors: Butković Anamarija , González Rubén , Rivarez Mark Paul Selda , Elena Santiago F
Published: June 2021

Viruses lie in a continuum between generalism and specialism depending on their ability to infect more or less hosts. While generalists are able to successfully infect a wide variety of hosts, specialists are limited to one or a few. Even though generalists seem to gain an advantage due to their wide host range, they usually pay a pleiotropic fitness cost within each host. On the contrary, a specialist has maximal fitness within its own host. A relevant yet poorly explored question is whether viruses differ in the way they interact with their hosts’ gene expression depending on their degree of specialization. Using a genome-wide association study approach, we have identified host genes whose expression depends on whether hosts were infected with more or less specialized viral strains. Four hundred fifty natural accessions of Arabidopsis thaliana were inoculated with Turnip mosaic potyvirus strains with different past evolutionary histories and that shown different degrees of specialization. Three disease-related traits were measured and associated with different sets of host genes for each strain. The genetic architectures of these traits differed among viral strains and, in the case of the more specialized virus, also varied along the duration of infection. While most of the mapped loci were strain specific, one shared locus was mapped for both strains, a disease-resistance TIR-NBS-LRR class protein. Likewise, only putative cysteine-rich receptor-like protein kinases were involved in all three traits. The impact on disease progress of 10 selected genes was validated by studying the infection phenotypes of loss-of-function mutant plants. Nine of these mutants have altered the disease progress and/or symptoms intensity between both strains. Compared to wild-type plants six had an effect on both viral strains, three had an effect only on the more specialized, and two were significant during infection with the less specialized.
Does Local Female Political Representation Empower Women to Run for Higher Office? Evidence from State and National Legislatures in India
Authors: Brown Ryan , Mansour Hani , O’Connell Stephen D
Published: June 2021

Does increasing the number of women in career stages that precede high-level positions affect female representation at the top of the career ladder? State legislature elections narrowly won by female candidates in India are exploited to examine the effect of expanding the pipeline of women in local politics on subsequent female representation and success in national legislature elections. For each additional state legislature election won by a woman, there is a 34 percent increase in the number of female candidates contesting in the subsequent national election, and a 2.6 percentage-point increase in the average vote share won per female candidate. This relationship is driven by new female politicians and not by the progression of female state legislators nor by continued candidacy of previous female candidates for the national legislature.
Myeloid Cell Infiltration Correlates With Prognosis in Cholangiocarcinoma and Varies Based on Tumor Location
Authors: Kunk Paul R. , Dougherty Sean C. , Lynch Kevin , Whitehair Rachel , Meneveau Max , Obeid Joseph M. , Winters Kevin , Ju Jennifer Y. , Stelow Edward B. , Bauer Todd W. , Slingluff Craig L. , Rahma Osama E.
Published: June 2021

Cholangiocarcinoma (CC) is an uncommon malignancy with increasing incidence and dismal prognosis. We conducted a comprehensive analysis of the CC tumor immune microenvironment (TIME) based on tumor location to identify therapeutic targets. We hypothesized that the TIME of CC would vary by primary tumor location and that high tumor infiltration by CD8+ T cells and low infiltration by M2 macrophages would be associated with improved survival. A retrospective analysis was conducted of 99 CC tumor samples surgically resected between 2000 and 2014. Tissue microarrays were constructed from each tumor and stained by immunohistochemistry for 24 markers of immune cells, immune activation or inhibition, programmed cell death-ligand 1, and mesothelin. Most tumors were amply infiltrated with by CD4+, CD8+, and FoxP3+ T cells, as well as by myeloid cells. Mesothelin expression ≥1+ by immunohistochemistry was found in 68% of tumors. We identified higher densities of M1 macrophages in primary distal extrahepatic CC, as well as metastatic lesions. Mesothelin expression was also significantly higher in distal extrahepatic CC. There was no association with survival of infiltration by CD4+, CD8+, or FoxP3+ T cells, mesothelin expression, or programmed cell death-ligand 1 percentage expression, however, high CD14+ myeloid cells and high CD163+ M2 macrophages were associated with worse survival. In conclusion, the CC TIME is a heterogenous milieu highly infiltrated by innate and adaptive immune cells, which differs based on primary tumor location and between primary tumors and metastatic lesions. The correlation of intratumoral M2 macrophages and myeloid cells with a worse prognosis may suggest promising immunotherapeutic targets in CC.
An Innovative Palatoplasty for Primary Cleft Palate Repair
Authors: Rossell-Perry Percy
Published: June 2021

Many surgical techniques have been developed to restore function in patients with cleft palate. Despite the development of many surgical techniques for primary cleft palate repair there is no standard procedure that ensures palatal function as that in normal children. Furlow’s and intravelar veloplasty are the most common methods for velar repair in patients with cleft palate; however, some limitations have been described by different authors. The objective of this study was to present an innovative method for primary cleft palate repair that addresses the shortcomings of conventional methods. Since 2017, 88 consecutive patients with nonsyndromic unilateral cleft palate have undergone primary anatomical repair of palatal deformity using this technique. This method combines nasal mucosa Z plasty and muscular overlapping with the use of one hemiuvula for uvular repair (unilateral uvuloplasty). The nasal mucosa Z plasty produces velar lengthening by transposition of nasal mucosa and myomucosal flaps. The unilateral uvuloplasty reduces anatomically the velopharyngeal gap and increases the velar length, thus reducing velopharyngeal distance. This innovative palatoplasty, achieves proper anatomical and functional reconstruction of the repaired palate. Only four patients (4.54%) developed mild or severe hypernasality and one patient (1.13%) had postoperative palatal fistula in this group of patients. This innovative technique results in low rates of nondesirable outcomes, improving limitations of conventional methods. Reduced oral mucosa incisions, limited velar muscle dissection, and preservation of the tensor veli palatini anatomy are some of the benefits of this technique.
The Objective Effect of Breast Implant Removal and Capsulectomy on Pulmonary Function
Authors: Wee Corinne E. , Younis Joseph , Boas Samuel , Isbester Kelsey , Smith Arvin , Harvey Donald J. , Patil Nirav , Kumar Anand R. , Feng Lu-Jean
Published: June 2021

Background:

Breast Implant Illness after aesthetic breast augmentation remains a poorly-defined syndrome. Prior published studies have identified difficulty breathing as a symptom, but definitive improvement in breathing following breast implant removal remains understudied. We hypothesized that patients presenting with breathing symptoms attributed to breast implants would have objective improvement in pulmonary function tests after complete implant/capsule explantation.

Methods:

A retrospective study of all patients who underwent investigation for symptomatic breast implants by a single surgeon over 2 years was conducted. Paired T-tests were used to compare PFTs before and after surgery. Multivariate analyses and linear regression models were used to examine the impact of patient- and implant-related factors, including size and texture on PFT changes.

Results:

Sixty-nine patients met inclusion criteria. Forced vital capacity (mean pre: 3.67 ± 0.61 L versus post: 3.82 ± 0.55 L), forced expiratory volume (2.78 ± 0.44 L versus 2.89 ± 0.39 L), and peak expiratory flow rate (5.91 ± 1.43 L versus 6.56 ± 0.96 L) were significantly improved postoperatively (P = 0.004, 0.01, 0.0001, respectively). Textured implants were associated with a greater improvement in PFTs after their removal (P = 0.009). Implant size and capsular contracture, even when controlled relative to body mass index, were not independent predictors of improvement.

Conclusions:

This study demonstrates that patients presenting with symptomatic breast implants with pulmonary complaints had significant improvement in pulmonary function after complete implant/capsule explantation. Forced vital capacity, forced expiratory volume, and peak expiratory flow rate consistent with a restrictive pattern of ventilation reliably improved in this symptomatic cohort. Textured implants were a significant predictive variable for improvement in pulmonary function.
CLINICAL FEATURES AND OUTCOMES OF INFANTS WITH RETINOPATHY OF PREMATURITY WHO FAIL ANTIVASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY
Authors: Xu Lucy T. , Levine David A. , Hutchinson Amy K. , Rao Prethy , Hubbard George B.
Published: June 2021

Purpose:

To describe characteristics and outcomes of patients with retinopathy of prematurity who failed intravitreal antivascular endothelial growth factor.

Methods:

A retrospective case series of 211 eyes (112 patients) treated with antivascular endothelial growth factor as initial therapy for retinopathy of prematurity at a single academic institution between 2011 and 2019 and an additional 6 eyes (3 patients) referred to us for management of failed antivascular endothelial growth factor.

Results:

Among the 211 eyes receiving initial treatment at our institution, 17 eyes (11%) failed. Of the 23 total eyes managed by us for failure, 3 eyes (13%) failed after 50-week postmenstrual age. Failure manifested as recurrent plus in 14 eyes (58%), recurrent Stage 3 in 13 eyes (54%) and retinal detachment in 5 eyes (21%). Treatment failures were managed with laser (13 eyes), repeat injection (4 eyes), vitrectomy (2 eyes), or a combination of modalities (4 eyes). Follow-up of ≥6 months was available for 18 of the 23 eyes. The retina was fully attached in 17 eyes, and fixation behavior was present in 10 eyes.

Conclusion:

The most common manifestations of treatment failure were recurrent plus and Stage 3. The failure rate at our institution was 11.0%. A significant proportion of failures occurred after 50-week postmenstrual age. Most failed eyes had favorable anatomical outcomes and over half demonstrated fixation behavior.
Maximal lymph nodal diameter on N stage of nasopharyngeal carcinoma
Authors: Huang Shi-Ting , Qu Song , Li Ling , Chen Kai-Hua , Zhu Xiao-Dong , Pan Xin-Bin
Published: June 2021

To assess the maximal lymph nodal diameter on the 8th edition American Joint Committee on Cancer staging system of nasopharyngeal carcinoma (NPC).

This study extracted NPC patients between 2004 and 2016 in the Surveillance, Epidemiology, and End Results database. Included patients were divided into 3 groups: ≤3 cm, >3–6 cm, and >6 cm based on the maximal lymph nodal diameter. Cumulative survival curves of 5-year overall survival (OS) and cancer-specific survival (CSS) were calculated using the Kaplan-Meier method between the 3 groups.

The 5-year OS (64.0% vs 59.3%, P = .240) and CSS (71.8% vs 67.0%, P = .242) of ≤3 cm and >3–6 cm groups were not different. In contrast, the 5-year OS and CSS were different between >6 cm and ≤3 cm groups, and between >6 cm and >3–6 cm groups. The stratified hazard ratio of OS and CSS was 1.75 (95% confidence interval: 1.25–2.45; P = .001) and 1.77 (95% confidence interval: 1.20–2.60; P = .004) for the >6 cm group in the multivariate regression analysis.

It is reasonable that the maximal lymph nodal diameter with >6 cm is classified as stage N3 of the 8th edition American Joint Committee on Cancer staging system for NPC.
HIV infection and risk of COVID-19 mortality
Authors: Dong Yonghai , Li Zhongjian , Ding Sheng , Liu Shulong , Tang Zhiyuan , Jia Lina , Liu Jiahong , Liu Yun
Published: June 2021

Background:

This meta-analysis aimed to estimate the association of human immunodeficiency virus (HIV) infection and risk of coronavirus disease 2019 (COVID-19) mortality.

Methods:

We systematically retrieved articles published on HIV infection and risk of COVID-19 mortality through PubMed, EMBase, China National Knowledge Infrastructure, WanFang, and Chongqing VIP databases using a predefined search strategy from December 1, 2019 to January 31, 2021. Newcastle–Ottawa Scale (NOS) was used to assess the quality of the included studies. Cochran Q test and I
2 statistics were quantified to measure heterogeneity. Odds ratio (OR) and 95% confidence intervals (CI) were computed and displayed in the form of forest plots. Subgroup analysis was performed to explore the source of heterogeneity. Funnel plot, Begg test, and Egger test were used to assess potential publication bias. Stata software version 11.0 was used to analyze all the statistical data.

Results:

We included 10 studies with 18,122,370 COVID-19 patients, of whom 41,113 were with HIV infection and 18,081,257 were without HIV infection. The pooled overall results suggested that people living with HIV infection had a higher risk of mortality from COVID-19 than those without HIV infection (OR = 1.252, 95% CI 1.027–1.524). Subgroup analysis showed that people living with HIV infection had a higher risk of COVID-19 mortality than those without HIV infection in the United States (OR = 1.520, 95% CI 1.252–1.845) and in South Africa (OR = 1.122, 95% CI 1.032–1.220); however, no significant association was found in the United Kingdom (OR = 0.878, 95% CI 0.657–1.174).

Conclusion:

Patients with HIV infection should be the emphasis population to prevent the risk of mortality during the clinical treatment of COVID-19 patients.
Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes (MELAS) Syndrome
Authors: Galnares-Olalde Javier A. , López-Hernández Juan C. , Benitez-Alonso Edmar O. , de Montellano David J.D.-O. , May-Mas Raúl N. , Briseño-Godínez María E. , Pérez-Valdez Esther Y. , Pérez-Jovel Enrique , Fernández-Valverde Francisca , León-Manríquez Elizabeth , Vargas-Cañas Edwin S.
Published: June 2021

Introduction:

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome, is a multisystemic entity of mitochondrial inheritance. To date, there is no epidemiological information on MELAS syndrome in Mexico.

Case Series:

A retrospective, cross-sectional design was employed to collect and analyze the data. The clinical records of patients with mitochondrial cytopathies in the period ranging from January 2018 to March 2020 were reviewed. Patients who met definitive Yatsuga diagnostic criteria for MELAS syndrome were included to describe frequency, clinical, imaging, histopathologic, and molecular studies. Of 56 patients diagnosed with mitochondrial cytopathy, 6 patients met definitive Yatsuga criterion for MELAS (10.7%). The median age at diagnosis was 34 years (30 to 34 y), 2 females and the median time from onset of symptoms at diagnosis 3.5 years (1 to 10 y). The median of the number of stroke-like episodes before the diagnosis was 3 (range, 2 to 3). The main findings in computed tomography were basal ganglia calcifications (33%), whereas in magnetic resonance imaging were a lactate peak in the spectroscopy sequence in 2 patients. Five patients (84%) had red-ragged fibers and phantom fibers in the Cox stain in the muscle biopsy. Four patients (67%) had presence of 3243A>G mutation in the mitochondrial MT-TL1 gene. One patient died because of status epilepticus.

Conclusions:

MELAS syndrome represents a common diagnostic challenge for clinicians, often delaying definitive diagnosis. It should be suspected in young patients with stroke of undetermined etiology associated with other systemic and neurological features.
Correcting Wide Alar Base and Flare With Combined Sill and Alar Excision in Asian Patients
Authors: Yu Bao-Fu , Li Shu-Qiang , Chen Xiao-Xue , Wei Jiao , Dai Chuan-Chang
Published: June 2021

Background:

Obvious scar and deformities are commonly observed with incision anterior to the alar-facial groove in alar excision surgery. The authors explored modified sill and alar excision to correct wide alar base and flare synchronously and decreased incident of unacceptable scar and deformities in Asian patients.

Methods:

The authors conducted a retrospective cohort study including 52 consecutive patients undergoing this surgery. Contrary to previous studies, the incision for alar excision was located in the alar-facial groove and was closed by intracutaneous suture. Scars were assessed with visual analog scale and the Stony Brook Scar Evaluation Scale. Ratio of the interalar distance to intercanthal distance, nostril shape, and nostril symmetry was recorded.

Results:

The mean follow-up time was 18 months. Visual analog scale results showed 50 patients (96.2%) reported unnoticeable scar and 2 noticeable but acceptable scar. Stony Brook Scar Evaluation Scale results indicated 49 patients (94.2%) with good scar outcomes and 3 (5.8%) with moderate scar outcomes. The mean ratio of interalar distance to intercanthal distance reduced significantly from preoperative 1.10 to postoperative 1.02. The frequency of horizon-shaped nostrils changed from preoperative 16 cases (30.8%) to postoperative 2 cases (3.8%). The frequency of the pear-shaped (preferred shape) nostrils improved from preoperative 15 cases (28.8%) to postoperative 26 cases (50.0%). The frequency of symmetrical nostril shape improved from preoperative 36 patients (69.2%) to 42 (80.8%). There were no patients with complications like alar deformities, and patients’ dissatisfaction.

Conclusions:

When performing sill and alar excision in Asian patients, the authors recommended a modified approach with the incision for alar excision being placed in the alar-facial groove and closed by intracutaneous suture, which can avoid obvious scar and deformities in Asian patients.

Level of evidence: Level 4.
Alcohol and Drug Use While Cycling Significantly Increases the Likelihood of Facial Fractures
Authors: Sorenson Thomas J. , Rich Matthew D. , Hagstrom Michael , Lamba Abhinav , Barta Ruth J. , Schubert Warren
Published: June 2021

Purpose:

Substance use, including alcohol and drugs, has been found to amplify the risks associated with cycling. Our purpose was to determine the relationship between alcohol or drug use and facial injuries in a nationwide population of patients experiencing cycling trauma.

Methods:

The authors report a cross-sectional study of patients reported to the National Electronic Injury Surveillance System from January 1, 2019 to December 31, 2019, in the United States. Patients were included in our study if they were evaluated in the emergency department for a cycling-related injury. Primary outcome was facial injury.

Results:

There were a total of 6499 adult patients who experience an injury after cycling trauma reported by the National Electronic Injury Surveillance System-participating emergency departments during the study period. A total of 553 (553/6499; 8.5%) patients had a facial injury and 82 patients with facial injuries had alcohol/drug use recorded (82/553; 14.8%). The proportion of males with facial injuries was higher in the alcohol/drug group than the no alcohol/drug group (86.6% versus 76.4%, respectively; P = 0.04). Injured cyclists in the alcohol/drug group experienced greater odds of sustaining a facial injury (odds ratio: 2.21, 95% confidence interval: 1.71–2.84, P < 0.0001) and a facial fracture (odds ratio: 2.75, 95% confidence interval: 1.83–4.13, P < 0.0001) than injured cyclists in the no alcohol/drug group.

Conclusions:

Substance use while cycling is not safe and significantly increases the likelihood of a facial injury and of facial fractures. This prevalence of injuries would suggest that cycling under the influence should always be illegal, and the law strictly enforced.
A mathematical model of the dynamics of lymphatic filariasis in Caraga Region, the Philippines
Authors: Salonga Pamela Kim N. , Mendoza Victoria May P. , Mendoza Renier G. , Belizario Vicente Y.
Published: June 2021

Despite being one of the first countries to implement mass drug administration (MDA) for elimination of lymphatic filariasis (LF) in 2001 after a pilot study in 2000, the Philippines is yet to eliminate the disease as a public health problem with 6 out of the 46 endemic provinces still implementing MDA for LF as of 2018. In this work, we propose a mathematical model of the transmission dynamics of LF in the Philippines and a control strategy for its elimination using MDA. Sensitivity analysis using the Latin hypercube sampling and partial rank correlation coefficient methods suggests that the infected human population is most sensitive to the treatment parameters. Using the available LF data in Caraga Region from the Philippine Department of Health, we estimate the treatment ratesr1andr2using the least-squares parameter estimation technique. Parameter bootstrapping showed small variability in the parameter estimates. Finally, we apply optimal control theory with the objective of minimizing the infected human population and the corresponding implementation cost of MDA, using the treatment coverageγas the control parameter. Simulation results highlight the importance of maintaining a high MDA coverage per year to effectively minimize the infected population by the year 2030.
Replay of innate vocal patterns during night sleep in suboscines
Authors: Döppler Juan F. , Peltier Manon , Amador Ana , Goller Franz , Mindlin Gabriel B.
Published: June 2021

Activation of forebrain circuitry during sleep has been variably characterized as ‘pre- or replay’ and has been linked to memory consolidation. The evolutionary origins of this mechanism, however, are unknown. Sleep activation of the sensorimotor pathways of learned birdsong is a particularly useful model system because the muscles controlling the vocal organ are activated, revealing syringeal activity patterns for direct comparison with those of daytime vocal activity. Here, we show that suboscine birds, which develop their species-typical songs innately without the elaborate forebrain–thalamic circuitry of the vocal learning taxa, also engage in replay during sleep. In two tyrannid species, the characteristic syringeal activation patterns of the song could also be identified during sleep. Similar to song-learning oscines, the burst structure was more variable during sleep than daytime song production. In kiskadees (
Pitangus sulphuratus
), a second vocalization, which is part of a multi-modal display, was also replayed during sleep along with one component of the visual display. These data show unambiguously that variable ‘replay’ of stereotyped vocal motor programmes is not restricted to programmes confined within forebrain circuitry. The proposed effects on vocal motor programme maintenance are, therefore, building on a pre-existing neural mechanism that predates the evolution of learned vocal motor behaviour.
Cancer risk algorithms in primary care: can they improve risk estimates and referral decisions?
Authors: Kostopoulou Olga , Arora Kavleen , Pálfi Bence
Published: June 2021

Background

Cancer risk calculators were introduced to clinical practice in the last decade, but they remain underused. We aimed to test their potential to improve risk assessment and 2-week-wait referral decisions.

Methods

157 GPs were presented with 23 vignettes describing patients with possible colorectal cancer symptoms. GPs gave their intuitive risk estimate and inclination to refer. They then saw the risk score of an algorithm (QCancer was not named) and could update their responses. Half of the sample was given information about the algorithm’s derivation, validation, and accuracy. At the end, we measured their algorithm disposition.

Results

GPs changed their inclination to refer 26% of the time and switched decisions entirely 3% of the time. Post-algorithm decisions improved significantly vis-à-vis the 3% NICE threshold (OR 1.45 [1.27, 1.65], p<.001). The algorithm’s impact was greater where GPs had underestimated risk. GPs who received information about the algorithm had more positive disposition towards it. A learning effect was observed: GPs’ intuitive risk estimates became better calibrated over time, i.e., moved closer to QCancer.

Conclusions

Cancer risk calculators have the potential to improve 2-week-wait referral decisions. Their use as learning tools to improve intuitive risk estimates is promising and should be further investigated.
CYP2D6 Genotyping for Personalized Therapy of Tamoxifen in Indonesian Women with ER+ Breast Cancer
Authors: Maggadani Baitha Palanggatan , Junusmin Kathleen Irena , Sani Levana L. , Mahendra Caroline , Amelia Margareta , Gabriella  , Irwanto Astrid , Harmita  , Harahap Yahdiana , Haryono Samuel J.
Published: June 2021

Tamoxifen is a Selective Estrogen-Receptor Modulator (SERM) commonly prescribed for standard of care in estrogen receptor positive (ER+) breast cancer as an adjuvant therapy. Tamoxifen is metabolized by CYP2D6 into its active metabolite, endoxifen, which has been known to play an important role in reducing risk of ER+ breast cancer recurrence. CYP2D6 is a highly polymorphic gene with more than 100 alleles. The phenotype of this gene is categorized into ultrarapid metabolizer (UM), normal metabolizer (NM), intermediate metabolizer (IM), and poor metabolizer (PM). Certain CYP2D6 polymorphisms may cause reduced activity of this enzyme. Studies have found that reduced CYP2D6 activity in IM and PM patients causes low efficacy of standard tamoxifen therapy. This study aims to observe the distribution of CYP2D6 alleles and its correlation with endoxifen levels in Indonesian ER+ breast cancer patients. 151 patients who have received tamoxifen therapy for at least eight weeks were recruited prospectively. DNA and blood samples were collected with buccal swab and finger-prick methods, respectively. Genotyping was performed using the qPCR method while metabolite level measurement was performed using high performance liquid chromatography tandem mass spectrometry. We found that 40.67% of ER+ breast cancer patients recruited were IM. CYP2D6*10 was the most abundant allele (0.288) in this population, and *10/*36 was the most frequently observed diplotype (0.236). Endoxifen levels between the NM-PM, NM-IM, and IM-PM were statistically significant (p-value = 6.26 × 10−5, 9.12 × 10−5, and 4.714 × 10−3, respectively), and dose increase of tamoxifen to 40 mg daily successfully increased endoxifen levels in IMs to a similar level with NMs at baseline. Given these findings, implementing pharmacogenomic testing of CYP2D6 on ER+ breast cancer women who are about to undergo tamoxifen therapy may be beneficial to increase the likelihood of achieving expected endoxifen levels, thus better treatment efficacy.