bluuebunny/crossref_metadata_2025 huggingface dataset:
Horizontalizing Insecurity or Securitizing Privacy? Two Narratives of a Rule-of-Law Misalignment between a Special Administrative Region and Its State
Authors: Vecellio Segate Riccardo
Published: January 2022

Data protection is generally surmised as antithetical to State surveillance and regulatory intrusiveness into the measures that businesses adopt to ensure the security of personal data. This originates in an ancient, West-rooted understanding of the ‘rule of law’ as the ultimate shield of ‘the private’ sphere against ‘the public’ sovereign power. Therefore, through Western lenses, data protection and State securitization of citizens’ data cannot be but a dichotomy. This article challenges such a presumption, arguing that a no less legitimate view of what the ‘rule of law’ stands for gives rise to both a vertical and a horizontal attitude towards privacy regulation. By scrutinizing the Cathay Pacific data breach and its consequences for passengers’ records in terms of corporate liability, this analysis posits that China and one of its special administrative regions, Hong Kong, display the facets of a horizontal and vertical policy approach to data protection respectively. Comparative observations demonstrate that against a context of increasingly pervasive cyberattacks, a fair degree of State oversight in corporate cyberspace regulation is not necessarily to be rejected. In fact, State ‘interventionism’ to prevent cyberattacks seems a legitimate outlook on data protection, which, while possibly impairing citizens’ privacy vertically vis-à-vis the government, greatly enhances such a privacy horizontally by constraining exposure to data misappropriation by non-governmental (home and foreign) cybercriminals. These two ‘Chinese’ approaches can be synthesized and might, indeed, coalesce into an international rule of law, to be based on moderate State assertiveness to prevent data breaches in the cyberspace.
The Thiopurine Tale: An Unexpected Journey
Authors: Crouwel Femke , Buiter Hans J C , de Boer Nanne K
Published: January 2022

Exactly 70 years ago [1951] mercaptopurine was discovered by Gertrude Elion as a novel treatment option for acute leukaemia. A total of three thiopurines (also thioguanine [1950] and azathioprine [1957]) were developed over time. These immunosuppressive drugs were also successfully introduced a few decades later to prevent rejection of transplanted organs and to treat several autoimmune diseases. For her discovery of thiopurines and other antimetabolite drugs, in 1988 Elion was rewarded, together with George Hitchings and James Black, with the Nobel Prize in Physiology or Medicine. Important steps have been made in recent years to unravel its metabolism, mode of action and pharmacogenetics. Today thiopurine [based] therapy remains an essential immunosuppressive approach in treating patients with inflammatory bowel disease.
Sensory Disabilities and Social Isolation Among Hispanic Older Adults: Toward Culturally Sensitive Measurement of Social Isolation
Authors: Trujillo Tanner Corinna , Yorgason Jeremy B , Richardson Stephanie , Redelfs Alisha H , Serrao Hill Melanie M Y , White Avalon , Stagg Brian , Ehrlich Joshua R , Markides Kyriakos S
Published: January 2022

Objectives

Sensory disabilities, including vision disability and hearing disability, increase risk for social isolation, which is associated with multiple negative health outcomes. Existing literature suggests that the cultural value of familism may provide a buffer against social isolation. We examined the longitudinal trajectory of social isolation among Hispanic older adults with self-reported vision disability (SRVD) and self-reported hearing disability and tested a modified measure of social isolation incorporating familism.

Methods

We compared 8-year trajectories of social isolation among Hispanics (n = 445) and non-Hispanic Whites (n = 4,861) from the National Health and Aging Trends Study. We used structural equation modeling to explore the longitudinal relationships between sensory disability and social isolation while comparing 2 measures of social isolation.

Results

Social isolation increased longitudinally for both groups, with SRVD significantly associated with higher initial levels. Social isolation started and remained higher across time among Hispanics. Using an adjusted measure of social isolation (added familial support), neither initial levels nor trajectories of social isolation differed between Hispanic and non-Hispanic White participants.

Discussion

Initially, Hispanics appeared more socially isolated, reporting less social support from outside the home. Yet, we found that they were more likely to report family social connections. Traditional measures of social isolation focusing on social support outside of the home (neglecting support by family) may lack content validity among Hispanic groups. Culturally sensitive measures of social isolation will be increasingly consequential for future research and health policy to meet the needs of a diverse older population.
Accounting for nonlinear effects of gene expression identifies additional associated genes in transcriptome-wide association studies
Authors: Lin Zhaotong , Xue Haoran , Malakhov Mykhaylo M , Knutson Katherine A , Pan Wei
Published: January 2022

Transcriptome-wide association studies (TWAS) integrate genome-wide association study (GWAS) data with gene expression (GE) data to identify (putative) causal genes for complex traits. There are two stages in TWAS: in Stage 1, a model is built to impute gene expression from genotypes, and in Stage 2, gene–trait association is tested using imputed gene expression. Despite many successes with TWAS, in the current practice, one only assumes a linear relationship between GE and the trait, which however may not hold, leading to loss of power. In this study, we extend the standard TWAS by considering a quadratic effect of GE, in addition to the usual linear effect. We train imputation models for both linear and quadratic gene expression levels in Stage 1, then include both the imputed linear and quadratic expression levels in Stage 2. We applied both the standard TWAS and our approach first to the ADNI gene expression data and the IGAP Alzheimer’s disease GWAS summary data, then to the GTEx (V8) gene expression data and the UK Biobank individual-level GWAS data for lipids, followed by validation with different GWAS data, suitable model checking and more robust TWAS methods. In all these applications, the new TWAS approach was able to identify additional genes associated with Alzheimer’s disease, LDL and HDL cholesterol levels, suggesting its likely power gains and thus the need to account for potentially nonlinear effects of gene expression on complex traits.
The changing tide of human fertility
Authors: Aitken R John
Published: January 2022

Over the past half-century, the world has witnessed a steep decline in fertility rates in virtually every country on Earth. This universal decline in fertility is being driven by increasing prosperity largely through the mediation of social factors, the most powerful of which are the education of women and an accompanying shift in life’s purpose away from procreation. In addition, it is clear that environmental and lifestyle factors are also having a profound impact on our reproductive competence particularly in the male where increasing prosperity is associated with a significant rise in the incidence of testicular cancer and a secular decline in semen quality and testosterone levels. On a different timescale, we should also recognize that the increased prosperity associated with the demographic transition greatly reduces the selection pressure on high fertility genes by lowering the rates of infant and childhood mortality. The retention of poor fertility genes within the human population is also being exacerbated by the increased uptake of ART. It is arguable that all of these elements are colluding to drive our species into an infertility trap. If we are to avoid the latter, it will be important to recognize the factors contributing to this phenomenon and adopt the social, political, environmental and lifestyle changes needed to bring this situation under control.
Histologic Evaluation Using the Robarts Histopathology Index in Patients With Ulcerative Colitis in Deep Remission and the Association of Histologic Remission With Risk of Relapse
Authors: Park Jin , Kang Soo Jin , Yoon Hyuk , Park Jihye , Oh Hyeon Jeong , Na Hee young , Lee Hye Seung , Shin Cheol Min , Park Young Soo , Kim Nayoung , Lee Dong Ho
Published: January 2022

Background

This study prospectively evaluated the risk of relapse according to the status of histologic activity in patients with ulcerative colitis (UC) who achieved deep remission.

Methods

Patients with UC in clinical remission (partial Mayo score ≤1) and endoscopic remission (ulcerative colitis endoscopic index of severity ≤1) were enrolled. Rectal biopsies were performed in patients, and histologic remission was defined as a Robarts histopathology index of ≤3. Receiver-operating characteristic curve analysis was conducted to determine fecal calprotectin cutoff values for histologic remission. The cumulative risk of relapse was evaluated using the Cox proportional hazards model.

Results

Among the 187 patients enrolled, 82 (43.9%) achieved histologic remission. The best cutoff value of fecal calprotectin for predicting histologic remission was 80 mg/kg (area under the curve of 0.646, sensitivity of 74%, and specificity of 61%). Among 142 patients who were followed up for >3 months, 56 (39.4%) showed clinical relapse during a median of 42 weeks. The risk of relapse was lower in patients with histologic remission than in those with histologic activity (P = .026). In multivariable analysis, histologic remission (hazard ratio [HR], 0.551; 95% confidence interval [CI], 0.316-0.958; P = .035), elevated C-reactive protein levels (HR, 3.652; 95% CI, 1.400-9.526; P = .008), and history of steroid use (HR, 2.398; 95% CI, 1.196-4.808; P = .014) were significantly associated with clinical relapse.

Conclusions

In patients with UC who achieved clinical and endoscopic remission, histologic remission was independently associated with a lower risk of clinical relapse.
The Influence of Life History on the Response to Parasitism: Differential Response to Non-Lethal Sea Lamprey Parasitism by Two Lake Charr Ecomorphs
Authors: Firkus Tyler J , Goetz Frederick W , Fischer Gregory , Murphy Cheryl A
Published: January 2022

The energetic demands of stressors like parasitism require hosts to reallocate energy away from normal physiological processes to survive. Life history theory provides predictions about how hosts will reallocate energy following parasitism, but few studies provide empirical evidence to test these predictions. We examined the sub-lethal effects of sea lamprey parasitism on lean and siscowet lake charr, two ecomorphs with different life history strategies. Leans are shorter lived, faster growing, and reach reproductive maturity earlier than siscowets. Following a parasitism event of 4 days, we assessed changes to energy allocation by monitoring endpoints related to reproduction, energy storage, and growth. Results indicate that lean and siscowet lake charr differ considerably in their response to parasitism. Severely parasitized leans slightly increased their reproductive effort and maintained growth and energy storage, consistent with expectations based on life history that leans are less likely to survive parasitism and have shorter lifespans than siscowets making investing in immediate reproduction more adaptive. Siscowets nearly ceased reproduction following severe parasitism and showed evidence of altered energy storage, consistent with a strategy that favors maximizing long-term reproductive success. These findings suggest that life history can be used to generalize stressor response between populations and can aid management efforts.
Coping With Urban Habitats Via Glucocorticoid Regulation: Physiology, Behavior, and Life History in Stream Fishes
Authors: Kolonin Arseniy M , Bókony Veronika , Bonner Timothy H , Zúñiga-Vega J Jaime , Aspbury Andrea S , Guzman Alex , Molina Roberto , Calvillo Pilo , Gabor Caitlin R
Published: January 2022

As environments become urbanized, tolerant species become more prevalent. The physiological, behavioral and life-history mechanisms associated with the success of such species in urbanized habitats are not well understood, especially in freshwater ecosystems. Here, we examined the glucocorticoid (GC) profiles, life-history traits, and behavior of two species of fish across a gradient of urbanization to understand coping capacity and associated trade-offs. We studied the tolerant live-bearing Western Mosquitofish (Gambusia affinis) for two years and the slightly less tolerant, egg-laying, Blacktail Shiner (Cyprinella venusta) for one year. We used a water-borne hormone method to examine baseline, stress-induced, and recovery cortisol release rates across six streams with differing degrees of urbanization. We also measured life-history traits related to reproduction, and for G. affinis, we measured shoaling behavior and individual activity in a novel arena. Both species showed a trend for reduced stress responsiveness in more urbanized streams, accompanied by higher reproductive output. Although not all populations fit this trend, these results suggest that GC suppression may be adaptive for coping with urban habitats. In G. affinis, GC recovery increased with urbanization, and individuals with the lowest stress response and highest recovery had the greatest reproductive allotment, suggesting that rapid return to baseline GC levels is also an important coping mechanism. In G. affinis, urban populations showed altered life-history trade-offs whereas behavioral traits did not vary systematically with urbanization. Thus, these tolerant species of fish may cope with anthropogenically modified streams by altering their GC profiles and life-history trade-offs. These results contribute to understanding the mechanisms driving species-specific adaptations and thereby community structure in freshwater systems associated with land-use converted areas.
Effects of Sodium Benzoate, a D-Amino Acid Oxidase Inhibitor, on Perceived Stress and Cognitive Function Among Patients With Late-Life Depression: A Randomized, Double-Blind, Sertraline- and Placebo-Controlled Trial
Authors: Lin Chieh-Hsin , Wang Shi-Heng , Lane Hsien-Yuan
Published: January 2022

Background

Compared with adults with depression in the general population, elderly depressive patients are prone to poor treatment response, more side effects, and early withdrawal with current antidepressants (which principally modulate monoamines). Whether N-methyl-D-aspartate receptor enhancement can benefit treatment of late-life depression deserves study. This study aims to compare sodium benzoate (a D-amino acid oxidase inhibitor and an indirect N-methyl-D-aspartate receptor enhancer), sertraline (a selective serotonin reuptake inhibitor), and placebo in the treatment of late-life depression.

Methods

In this randomized, double-blind trial, 117 patients with major depressive disorder aged 55 years or older received 8-week treatment of 250–1500 mg/d of sodium benzoate, 25–150 mg/d of sertraline, or placebo in 2 medical centers. The primary outcome measures were Hamilton Depression Rating Scale and Perceived Stress Scale scores.

Results

Three treatments similarly decreased clinicians-rated Hamilton Depression Rating Scale scores. Compared with placebo, sodium benzoate but not sertraline substantially improved Perceived Stress Scale scores and cognitive function. Sertraline, but not benzoate, significantly reduced self-report Geriatric Depression Scale scores. Benzoate and placebo showed similar safety profiles, while sertraline was more likely to raise low-density lipoprotein than benzoate and placebo. Benzoate-treated patients were less likely to drop out than sertraline or placebo recipients.

Conclusions

Sertraline can reduce subjective depressive symptoms, while benzoate can decrease perceived stress, improve cognitive function, and enhance treatment adherence in late-life depression patients. The results show promise for D-amino acid oxidase inhibition as a novel approach for perceived stress and cognitive decline among patients with late-life depression.

Trial Registration

ClinicalTrials.gov Identifier: NCT03414931. Registered January 2016.
Intrauterine Fetal Demise in the Third Trimester of Pregnancy Associated With Mild Infection With the SARS-CoV-2 Delta Variant Without Protection From Vaccination
Authors: Guan Minhui , Johannesen Eric , Tang Cynthia Y , Hsu Albert L , Barnes Courtney L , Burnam Megan , McElroy Jane A , Wan Xiu-Feng
Published: January 2022

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a higher infection rate in pregnant women than age-matched adults. With increased infectivity and transmissibility, the Delta variant is predominant worldwide.

Methods

In this study, we describe intrauterine fetal demise in unvaccinated women with mild symptoms of SARS-CoV-2 Delta variant infection.

Results

Histology and elevated proinflammatory responses of the placenta suggest that fetal demise was associated with placental malperfusion due to Delta variant infection.

Conclusions

This study suggests that the Delta variant can cause severe morbidity and mortality to fetuses. Vaccination should continue to be advocated and will likely continue to reduce SARS-CoV-2 infection risks for pregnant women and their fetuses.
Pulmonary arterial pressure in fattened Angus steers at moderate altitude influences early postmortem mitochondria functionality and meat color during retail display
Authors: Zhai Chaoyu , Li Puma Lance C , Chicco Adam J , Omar Asma , Delmore Robert J , Geornaras Ifigenia , Speidel Scott E , Holt Tim N , Thomas Milton G , Mark Enns R , Nair Mahesh N
Published: January 2022

Pulmonary hypertension is a noninfectious disease of cattle at altitudes > 1524 m (5,000 ft). Mean pulmonary arterial pressures (PAP) are used as an indicator for pulmonary hypertension in cattle. High PAP cattle (≥50 mmHg) entering the feedlot at moderate elevations have lower feed efficiency as compared to low PAP cattle (< 50 mmHg). The impact of pulmonary arterial pressure on mitochondrial function, oxidative phosphorylation (OXPHOS) protein abundance, and meat color was examined using longissimus lumborum (LL) from high (98 ± 13 mmHg; n = 5) and low (41 ± 3 mmHg; n = 6) PAP fattened Angus steers (live weight of 588 ± 38 kg) during early postmortem period (2 and 48 h) and retail display (days 1 to 9), respectively. High PAP muscle had greater (P = 0.013) OXPHOS-linked respiration and proton leak-associated respiration than low PAP muscles at 2 h postmortem but rapidly declined to be similar (P = 0.145) to low PAP muscle by 48 h postmortem. OXPHOS protein expression was higher (P = 0.045) in low PAP than high PAP muscle. During retail display, redness, chroma, hue, ratio of reflectance at 630 and 580 nm, and metmyoglobin reducing activity decreased faster (P < 0.05) in high PAP steaks than low PAP. Lipid oxidation significantly increased (P < 0.05) in high PAP steaks but not (P > 0.05) in low PAP. The results indicated that high PAP caused a lower OXPHOS efficiency and greater fuel oxidation rates under conditions of low ATP demand in premortem beef LL muscle; this could explain the lower feed efficiency in high PAP feedlot cattle compared to low PAP counterparts. Mitochondrial integral function (membrane integrity or/and protein function) declined faster in high PAP than low PAP muscle at early postmortem. LL steaks from high PAP animals had lower color stability than those from the low PAP animals during simulated retail display, which could be partially attributed to the loss of muscle mitochondrial function at early postmortem by ROS damage in high PAP muscle.
Circ_0000190 sponges miR-382-5p to suppress cell proliferation and motility and promote cell death by targeting ZNRF3 in gastric cancer
Authors: Jiang Man , Mo Rui , Liu Chang , Wu Haijian
Published: January 2022

This study was to explore the role of circRNA_0000190 (circ_0000190) in gastric cancer (GC) progression. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot assay were applied to measure RNA and protein expression. 5-Ethynyl-2’-deoxyuridine (EdU) assay and cell counting kit-8 (CCK8) assay were implemented to analyze cell proliferation ability. Transwell assays were conducted to analyze cell motility. Cell ferroptosis was assessed using commercial kit. The target relationship between microRNA-382-5p (miR-382-5p) and circ_0000190 or zinc and ring finger 3 (ZNRF3) was verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Murine xenograft model was used to analyze the function of circ_0000190 in GC progression in vivo. Circ_0000190 was down-regulated in GC tissues and cell lines. Low expression of circ_0000190 predicted dismal prognosis in GC patients. Circ_0000190 overexpression inhibited the proliferation, migration and invasion and promoted Erastin- or ras selective lethal 3 (RSL3)-mediated ferroptosis in GC cells. MiR-382-5p was a target of circ_0000190, and circ_0000190 suppressed GC progression partly via serving as miR-382-5p sponge. ZNRF3 was a target of miR-382-5p, and miR-382-5p accelerated the proliferation, motility and restrained the ferroptosis of GC cells partly via regulating ZNRF3. Circ_0000190 overexpression restrained xenograft tumor growth in vivo. Collectively, Circ_0000190 suppressed GC progression via miR-382-5p-dependent regulation of ZNRF3.
Case series of mesh migration after rectopexy surgery for rectal prolapse
Authors: Marghich Omar , Benichou Benjamin , Amouzou Efoé-Ga Yawod Olivier , Maubert Alexandre , Etienne Jean Hubert , Benizri Emmanuel , Rahili Mohamed Amine
Published: January 2022

Mesh rectopexy for rectal prolapse can cause some serious mesh-related complications. Mesh migration into close viscera following rectopexy is rare. We report three cases of mesh migration after mesh rectopexy treated in our unit. The first patient presented with purulent discharge from the buttock 15 years after the rectopexy, the second patient presented with abdominal pain and pneumaturia also 15 years after the rectopexy and the third patient presented 22 years after the rectopexy with vaginal discharge. Diagnosis was made by physical examination, computed tomography scan, magnetic resonance imaging, cystoscopy or rectoscopy. The three patients underwent total removal of the meshes without any complications.
Risk Factors Associated With Various Severities of Suicidal and Non-Suicidal Self-Harm Among Israel Defense Forces Soldiers—A Nested Case–Control Study
Authors: Shakarchy Nizan , Tatsa-Laur Lucian , Kedem Ron , Ben Yehuda Ariel , Shelef Leah
Published: January 2022

Objective

Severe suicide attempt is a major risk factor for completed suicide. The aim of the present study was to focus on suicide behavior and timing to gain better understanding of these populations.

Method

The nested case–control retrospective study based on medical records of 246,866 soldiers, who demonstrated suicide attempts of varying severity, including death by suicide were compared with soldiers who did not demonstrate such behavior.

Results

Risk for death by suicide was associated with males, military seniority of less than 12 months. High frequency of visits with mental health care professionals was associated with being severe suicide attempters (SAs). Moderate suicide attempts were associated with being a male, visiting a primary care physician frequently, and belonging to one of the two latest immigrant groups in Israel (Ethiopians and former Soviet Union). Mild suicide attempts were associated with having a psychiatric diagnosis on the enlistment day, visiting a mental health care professional at high or average frequency, visiting a primary care physician at high or average frequency, being a male, and being born in the former Soviet Union. While the proportion of males demonstrating suicidal behavior was higher than the females’, severe SAs were higher among females. There was a clear tendency of female suicide attempters at all levels to act toward the end of their military service.

Conclusions

Although half of the SAs were females, their characteristics may be similar to those of the male SAs, contrary to the sex differences in suicide behavior among civilians.
Discordance in Tumor Mutation Burden from Blood and Tissue Affects Association with Response to Immune Checkpoint Inhibition in Real-World Settings
Authors: Sturgill Emma G , Misch Amanda , Jones Carissa C , Luckett Daniel , Fu Xiaotong , Schlauch Dan , Jones Suzanne F , Burris Howard A , Spigel David R , McKenzie Andrew J
Published: January 2022

Background

Tumor mutation burden (TMB), a biomarker for immune checkpoint inhibitor (CPI) response, is reported by both blood- and tissue-based next-generation sequencing (NGS) vendors. However, the agreement between TMB from blood (bTMB) and tissue (tTMB) in real-world settings, both in absolute value and association with CPI response, is not known.

Materials and Methods

This study utilizes Sarah Cannon’s precision medicine platform, Genospace, to harmonize clinico-genomic data from 17 206 patients with cancer with NGS results from September 2015 to August 2021. A subset of patients have both bTMB and tTMB results. Statistical analyses are performed in R and include (1) correlation (r) and concordance (ρ) between patient-matched bTMB-tTMB pairs, (2) distribution of total bTMB and tTMB values, and (3) association of bTMB and tTMB with time to CPI therapy failure.

Results

In 410 patient-matched bTMB-tTMB pairs, the median bTMB (m = 10.5 mut/Mb) was significantly higher than the median tTMB (m = 6.0 mut/Mb, P < .001) leading to conflicting “high” and “low” statuses in over one-third of cases at a threshold of 10 mut/Mb (n = 410). Significant differences were observed in the distribution of bTMB values from blood-NGS vendors, with guardant health (GH) reporting higher (m = 10.5 mut/Mb, n = 2183) than Foundation Medicine (FMI, m = 3.8 mut/Mb, n = 462, P < .001). bTMB from GH required a higher threshold (≥40 mut/Mb) than bTMB from FMI (≥12 mut/Mb) in order to be associated with CPI response.

Conclusions

This study uncovers variability in bTMB reporting among commercial NGS platforms, thereby evidencing a need for assay-specific thresholds in identifying patients who may respond to CPI therapy.
PlantNexus: A Gene Co-expression Network Database and Visualization Tool for Barley and Sorghum
Authors: Zhou Yadi , Sukul Abhijit , Mishler-Elmore John W , Faik Ahmed , Held Michael A
Published: January 2022

Global gene co-expression networks (GCNs) are powerful tools for functional genomics whereby putative functions and regulatory mechanisms can be inferred by gene co-expression. Cereal crops, such as Hordeum vulgare (barley) and Sorghum bicolor (sorghum), are among the most important plants to civilization. However, co-expression network tools for these plants are lacking. Here, we have constructed global GCNs for barley and sorghum using existing RNA-seq data sets. Meta-information was manually curated and categorized by tissue type to also build tissue-specific GCNs. To enable GCN searching and visualization, we implemented a website and database named PlantNexus. PlantNexus is freely available at https://plantnexus.ohio.edu/.
Molecular tug-of-war: Plant immune recognition of herbivory
Authors: Snoeck Simon , Guayazán-Palacios Natalia , Steinbrenner Adam D
Published: January 2022

Plant defense responses against insect herbivores are induced through wound-induced signaling and the specific perception of herbivore-associated molecular patterns (HAMPs). In addition, herbivores can deliver effectors that suppress plant immunity. Here we review plant immune recognition of HAMPs and effectors, and argue that these initial molecular interactions upon a plant–herbivore encounter mediate and structure effective resistance. While the number of distinct HAMPs and effectors from both chewing and piercing–sucking herbivores has expanded rapidly with omics-enabled approaches, paired receptors and targets in the host are still not well characterized. Herbivore-derived effectors may also be recognized as HAMPs depending on the host plant species, potentially through the evolution of novel immune receptor functions. We compile examples of HAMPs and effectors where natural variation between species may inform evolutionary patterns and mechanisms of plant–herbivore interactions. Finally, we discuss the combined effects of wounding and HAMP recognition, and review potential signaling hubs, which may integrate both sensing functions. Understanding the precise mechanisms for plant sensing of herbivores will be critical for engineering resistance in agriculture.
GentianFLOWERING LOCUS Torthologs regulate phase transitions: floral induction and endodormancy release
Authors: Takahashi Hideyuki , Nishihara Masahiro , Yoshida Chiharu , Itoh Kimiko
Published: January 2022

Perennial plants undergo a dormant period in addition to the growth and flowering phases that are commonly observed in annuals and perennials. Consequently, the regulation of these phase transitions in perennials is believed to be complicated. Previous studies have proposed that orthologs of FLOWERING LOCUS T (FT) regulate not only floral initiation but also dormancy. We, therefore, investigated the involvement of FT orthologs (GtFT1 and GtFT2) during the phase transitions of the herbaceous perennial gentian (Gentiana triflora). Analysis of seasonal fluctuations in the expression of these genes revealed that GtFT1 expression increased prior to budbreak and flowering, whereas GtFT2 expression was induced by chilling temperatures with the highest expression occurring when endodormancy was released. The expression of FT-related transcription factors, reportedly involved in flowering, also fluctuated during each phase transition. These results suggested the involvement of GtFT1 in budbreak and floral induction and GtFT2 in dormancy regulation, implying that the two gentian FT orthologs activated a different set of transcription factors. Gentian ft2 mutants generated by CRISPR/Cas9-mediated genome editing had a lower frequency of budbreak and budbreak delay in overwintering buds caused by an incomplete endodormancy release. Our results highlighted that the gentian orthologs of FRUITFULL (GtFUL) and SHORT VEGETATIVE PHASE-like 1 (GtSVP-L1) act downstream of GtFT2, probably to prevent untimely budbreak during ecodormancy. These results suggest that each gentian FT ortholog regulates a different phase transition by having variable responses to endogenous or environmental cues, leading to their ability to induce the expression of distinct downstream genes.
The mean-square radius of the neutron distribution in the relativistic and non-relativistic mean-field models
Authors: Kurasawa Haruki , Suzuki Toshio
Published: January 2022

It is investigated why the root-mean-square radius of the point neutron distribution is smaller by about 0.1 fm in non-relativistic mean-field models than in relativistic ones. The difference is shown to stem from the different values of the product of the effective mass and the strength of the one-body potential in the two frameworks. The values of those quantities are constrained by the Hugenholtz–Van Hove theorem. The neutron skin is not a simple function of the symmetry potential, but depends on the nucleon effective mass.
Applying Benford’s law to COVID-19 data: the case of the European Union
Authors: Kolias Pavlos
Published: January 2022

Background

Previous studies have used Benford’s distribution to assess the accuracy of COVID-19 data. Data inaccuracies provide false information to the media, undermine global response and hinder the preventive measures taken by authorities.

Methods

Daily new cases and deaths from all the countries of the European Union were analyzed and the conformance to Benford’s distribution was estimated. Two statistical tests and two measures of deviation were calculated to determine whether the reported statistics comply with the expected distribution. Four country-level developmental indexes were included, the GDP per capita, health expenditures, the Universal Health Coverage (UHC) Index and the full vaccination rate. Regression analysis was implemented to examine whether the deviation from Benford’s distribution is affected by the aforementioned indexes.

Results

The findings indicate that Bulgaria, Croatia, Lithuania and Romania were in line with Benford’s distribution. Regarding daily cases, Denmark, Ireland and Greece, showed the greatest deviation from Benford’s distribution. Furthermore, it was found that the vaccination rate is positively associated with deviation from Benford’s distribution.

Conclusions

The findings suggest that overall, official data provided by authorities are not confirming Benford’s law, yet this approach acts as a preliminary tool for data verification. More extensive studies should be made with a more thorough investigation of countries that showed the greatest deviation.
How Do Options Add Value? Evidence from the Convertible Bond Market
Authors: Lee Inmoo , Renjie Rex Wang , Verwijmeren Patrick
Published: January 2022

This paper studies the value relevance of the options market by focusing on convertible bond pricing. Pricing convertible bonds requires essentially the same set of information necessary to price options. Using a regression discontinuity design based on minimum stock price requirements for option listings, we find that the availability of stock options helps issuers attract more convertible bond buyers and reduces convertible issuers’ cost of financing. Our results highlight that the availability of individual stock options can add value to security issuers.
Towards improvement in malaria policy implementation in Nigeria: a qualitative study on factors influencing the translation of malaria policies to practice
Authors: Omo-Imafidon Evbogaghe S , Adeogun Adedapo O , Babalola Ayodele S , Okefu Philip O , Akinyemi Oluwaseun O
Published: January 2022

Background

Malaria is a severe health issue in Nigeria, particularly for pregnant women and children <5 y of age, despite all malaria control programs. From the standpoint of major stakeholders in Nigeria, this study explored both promoting and limiting factors affecting the implementation of malaria policy.

Methods

From March to June 2019, in-depth interviews were conducted with 16 key respondents. Key informants such as malaria researchers, policy advisers and program managers were identified using purposive and snowballing sampling strategies. Interviews were performed in English, recorded, transcribed and analysed using QSR NVivo 11.

Results

Some of the variables increasing the implementation of malaria policies in Nigeria, according to respondents, were political will, access to funds from donors, and staff commitment. Insufficient planning, lack of commitment, poor finance, manpower shortages, and a lack of synergy between academics and policymakers, on the other hand, were recognized as important barriers to the malaria policy implementation process by respondents.

Conclusions

Implementation gaps may result from a lack of capability for the policy implementation process and a lack of support for policy objectives. The difficulties in implementing malaria policy in Nigeria were highlighted in this study, and relevant recommendations were made.
Kounis Syndrome: A Review of an Uncommon Cause of Acute Coronary Syndrome
Authors: Douedi Steven , Odak Mihir , Mararenko Anton , Ross Jacqueline , Sealove Brett
Published: January 2022

Kounis syndrome is a hypersensitivity disorder secondary to allergy or anaphylaxis that can result in acute coronary syndrome. Kounis syndrome has an increasing prevalence since its first identification in 1950. Divided into 3 subtypes, each with diagnostic criteria, the management of Kounis syndrome presents a clinical challenge. We aim to identify the pathophysiological mechanisms and review the diagnosis, epidemiology, management strategies, and future directions of Kounis syndrome. As Kounis syndrome becomes more widely recognized in the medical community, the role of diagnosis, treatment, and future immunomodulatory prevention strategies will continue to unfold.
Clinicopathologic characteristics and risk factors for endometrial malignancy in postmenopausal women with endometrial thickening
Authors: Ai Fangfang , Wang Yiling , Zhou Liane , Wang Shijun
Published: January 2022

Objective:

To evaluate the clinicopathological characteristics and risk factors for endometrial malignancy in postmenopausal women with endometrial thickening.

Methods:

This was a retrospective study. Postmenopausal women with endometrial thickening (defined as the thickest endometrial portion in the sagittal uterine plane was greater than or equal to 5 mm) through transvaginal ultrasound in our outpatient department, and further referred to the gynecology department at Xuanwu Hospital for hysteroscopic diagnostic curettage assessment between January 2018 and March 2021 were included. According to the histopathological results, participants were divided into the benign group and malignant group. Univariate analysis was used to compare the differences in various factors, including demographics, clinical characteristics, medical complications, and ultrasound characteristics, between the two groups. Multiple logistic regression analysis was used to identify the factors that were independent contributors to the development of endometrial malignancy. Receiver operating characteristic analysis of endometrial thickness (ET) to predict endometrial malignancy was performed.

Results:

In total, 385 eligible cases were included in the analysis. The results suggested that older age (odds ratio [OR] 1.061, 95% confidence interval [CI] 1.008-1.116, P = 0.023), thicker ET (OR 5.032, 95% CI 2.453-10.322, P < 0.001), irregular menstruation in the past (OR 19.203, 95% CI 1.936-190.431, P = 0.012), postmenopausal bleeding (OR 12.341, 95% CI 4.440-34.302, P < 0.001), and polypoid mass-like lesions (OR 30.330, 95% CI 8.974-102.509, P < 0.001) were risk factors that were independently associated with the development of endometrial malignancy in postmenopausal women with increased ET. The optimal critical value of ET in predicting malignancy was 9.5 mm, and the sensitivity and specificity were 71.70% and 71.69%, respectively.

Conclusions:

For postmenopausal women with endometrial thickening, our results suggested that women who are older, have a thicker ET, had irregular menstruation in the past, have postmenopausal bleeding, and have polypoid mass-like lesions should seek medical attention as soon as possible and undergo further invasive examination. The use of 9.5 mm as the ET value to prompt investigations may be acceptable since it is unlikely to miss any atypical endometrial hyperplasia or endometrial cancer.
A challenging case of heparin-induced skin necrosis without thrombocytopenia
Authors: Chidharla Anusha , Rapoport Eliot A. , Naffakh Noor , Roberts Jonathan C.
Published: January 2022

Heparin-induced skin necrosis (HISN) is a rare complication of heparin anticoagulation. The condition occurs in various situations, including in heparin-naive and exposed individuals, in areas local or distant from the heparin injection site, and with or without frank thrombocytopenia. We present a case in which a patient treated for a pulmonary embolism with therapeutic unfractionated heparin (UFH) develops this adverse event. Symptoms were reversed with cessation of UFH and transition to bivalirudin without surgical debridement. The patient initially had anti-PF4 antibodies present but subsequent testing showed borderline antibodies and a negative serotonin release assay. After starting bivalirudin, the patient was later switched to fondaparinux without further consequences. This case illustrates the pathogenesis of HISN and provides an example of inconsistently abnormal laboratory values. Additionally, it provides two novel exposures the mRNA-1273 vaccine and the immune checkpoint inhibitor pembrolizumab that, to our knowledge, have not been previously reported.
Clinical Reasoning Behind Antibiotic Use in PICUs: A Qualitative Study*
Authors: Fontela Patricia S. , Gaudreault Josée , Dagenais Maryse , Noël Kim C. , Déragon Alexandre , Lacroix Jacques , Razack Saleem , Rennick Janet , Quach Caroline , McNally James D. , Carnevale Franco A. ,   on behalf of the Canadian Critical Care Trials Group
Published: January 2022

OBJECTIVES:

To describe the reasoning processes used by pediatric intensivists to make antibiotic-related decisions.

DESIGN:

Grounded theory qualitative study.

SETTING:

Three Canadian university-affiliated tertiary medical, surgical, and cardiac PICUs.

PATIENTS:

Twenty-one PICU physicians.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

We conducted field observation during morning rounds followed by semistructured interviews with participants to examine the clinical reasoning behind antibiotic-related decisions (starting/stopping antibiotics, or treatment duration) made for patients with a suspected/proven bacterial infection. We used a grounded theory approach for data collection and analysis. Thematic saturation was reached after 21 interviews. Of the 21 participants, 10 (48%) were female, 15 (71%) were PICU attending staff, and 10 (48%) had greater than 10 years in clinical practice. Initial clinical reasoning involves using an analytical approach to determine the likelihood of bacterial infection. In case of uncertainty, an assessment of patient safety is performed, which partly overlaps with the use of intuitive clinical reasoning. Finally, if uncertainty remains, physicians tend to consult infectious diseases experts. Factors that override this clinical reasoning process include disease severity, pressure from consultants, and the tendency to continue antibiotic treatment initiated by colleagues.

CONCLUSIONS:

Antibiotic-related decisions for critically ill children are complex, and pediatric intensivists use several clinical reasoning strategies to decrease the uncertainty around the bacterial etiology of infections. However, disease severity and patient safety concerns may overrule decisions based on clinical evidence and lead to antibiotic use. Several cognitive biases were identified in the clinical reasoning processes.
Brain aging and cardiovascular factors in HIV: a longitudinal volume and shape MRI study
Authors: Jakabek David , Rae Caroline D. , Brew Bruce J. , Cysique Lucette A.
Published: January 2022

Objective:

We aimed to examine the relative contributions of HIV infection, age, and cardiovascular risk factors to subcortical brain atrophy in people with HIV (PWH).

Design:

Longitudinal observational study.

Methods:

Virally suppressed PWH with low neuropsychological confounds (n 
= 75) and demographically matched HIV-negative controls (n = 31) completed baseline and 18-month follow-up MRI scans, neuropsychological evaluation, cardiovascular assessments, and HIV laboratory tests. PWH were evaluated for HIV-associated neurocognitive disorder (HAND). Subcortical volumes were extracted with Freesurfer after removal of white matter hyperintensities. Volumetric and shape analyses were conducted using linear mixed-effect models incorporating interactions between age, time, and each of HIV status, HAND status, HIV disease factors, and cardiovascular markers.

Results:

Across baseline and follow-up PWH had smaller volumes of most subcortical structures compared with HIV-negative participants. In addition, over time older PWH had a more rapid decline in caudate volumes (P 
= 0.041), predominantly in the more severe HAND subgroups (P = 0.042). Higher CD4+ cell counts had a protective effect over time on subcortical structures for older participants with HIV. Increased cardiovascular risk factors were associated with smaller volumes across baseline and follow-up for most structures, although a more rapid decline over time was observed for striatal volumes. There were no significant shape analyses findings.

Conclusion:

The study demonstrates a three-hit model of general (as opposed to localized) subcortical injury in PWH: HIV infection associated with smaller volumes of most subcortical structures, HIV infection and aging synergy in the striatum, and cardiovascular-related injury linked to early and more rapid striatal atrophy.
Cerebral Vasospasm-Left Heart Failure-Cerebral Infarction May Be a Potential Pathophysiological Mechanism of Malignant Cerebral Vasospasm
Authors: Sun Bing , Chang Hao , Ding Yasuo
Published: January 2022

Cerebral vasospasm (CV) and delayed cerebral ischemia are serious complications after ruptured aneurysm with high mortality and disability rate. However, there are few reports of cardiogenic CV, the mechanism is unclear, and the treatment recommended by the guidelines is not detailed. This article describes in detail a 47-year-old woman with intracranial aneurysm rupture and hemorrhage. After interventional operation, left heart failure worsened CV and cerebral infarction. This article summarizes the diagnosis and treatment process of patients in detail, summarizes the treatment strategies of cardiogenic CV, and elaborates the pathological mechanism of CV-left heart failure-CV and cerebral infarction. increase new understanding of the clinical diagnosis and treatment strategies of cardiogenic CV.
Twelve-Year Experience With Nasofrontal Angle (Radix) Augmentation in Rhinoplasty
Authors: Alawadh Ibrahim , Bogari Ahmad , Bedaiwi Reenad , Alanazi Hani , Bafaqeeh Sameer
Published: January 2022

The nasofrontal angle (radix) has a great impact on the rhinoplasty outcome. Minimal alterations in this area can give an unusual nasal appearance and midfacial length. Different management approaches have been described with regard to radix augmentation. This study aimed to describe the techniques of rhinoplasty, different materials used in the procedure, and results of at least 1 year of follow-up in our 12-year experience in this field. The authors retrospectively reviewed the data of patients who underwent rhino-plasty/septorhinoplasty with radix augmentation performed by 1 of the authors (a senior surgeon at our institution) using different graft materials, between January 2007 and December 2019. Patients younger than 18 years or who were followed up for less than 1 year were excluded from the study. In total, 387 patients (235 [60.7%] female; age range, 19–39 years) were included. Primary procedures were performed in 311 patients (80.5%), and revision procedures were performed in 76 patients (19.6%). Most patients (97%) were satisfied with the aesthetic result. There was no incidence of infection, displacement, or extrusion of the graft. The only complications observed were irregularities; 3% required revision surgery. It is important to consider the nasal radix when pursuing a balanced profile in rhinoplasty. Many graft materials can be used safely and can achieve good aesthetic outcomes. Proper anatomical analysis and patient selection are essential for successful graft placement.