bluuebunny/crossref_metadata_2025 huggingface dataset:
Infinitely many sign changes of the Liouville function on 𝑋²+𝐷
Authors: Srinivasan Anitha
Published: December 2021

We show that the Liouville functionλ\lambdachanges sign infinitely often onn2+dn^2+ dfor any non-zero integerdd.
Strong unfoldability, shrewdness and combinatorial consequences
Authors: Lücke Philipp
Published: December 2021

We show that the notions of strongly unfoldable cardinals, introduced by Villaveces [J. Symbolic Logic 63 (1998), pp. 1116–1136] in his model-theoretic studies of models of set theory, and shrewd cardinals, introduced by Rathjen [Bull. Symbolic Logic 1 (1995), pp. 468–485] in a proof-theoretic context, coincide. We then proceed by using ideas from the proof of this equivalence to establish the existence of ordinal anticipating Laver functions for strong unfoldability. With the help of these functions, we show that the principle

◊
κ

(

R
e
g

)

\Diamond _\kappa (\mathrm {Reg})

holds at every strongly unfoldable cardinal

κ
\kappa

with the property that there exists a subset

z
z

of

κ
\kappa

such that every subset of

κ
\kappa

is ordinal definable from

z
z

. While a result of Džamonja and Hamkins [Ann. Pure Appl. Logic 144 (2006), pp. 83–95] shows that

◊
κ

(

R
e
g

)

\Diamond _\kappa (\mathrm {Reg})

can consistently fail at a strongly unfoldable cardinal

κ
\kappa

, this implication can be used to prove that various canonical extensions of the axioms of

Z
F
C

\mathrm {ZFC}

are either compatible with the assumption that

◊
κ

(

R
e
g

)

\Diamond _\kappa (\mathrm {Reg})

holds at every strongly unfoldable cardinal

κ
\kappa

or outright imply this statement. Finally, we will also use our methods to contribute to the study of strong chain conditions of partials orders and their productivity.
On chain recurrence classes of endomorphisms of ℙ^{𝕜}
Authors: Taflin Johan
Published: December 2021

We prove that the minimal chain recurrence classes of a holomorphic endomorphism of

P

k

\mathbb {P}^k

have finitely many connected components. We also obtain results on arbitrary classes. These strong constraints on the topological dynamics in the phase space are all deduced from the associated action on a space of currents.
Socioeconomic disadvantage in multiple sclerosis: does inequality act on the substrate for disability?
Authors: Green Ari J
Published: December 2021

This scientific commentary refers to ‘Socioeconomic disparity is associated with faster retinal neurodegeneration in multiple sclerosis’ by Vasileiou et al. (doi:10.1093/brain/awab342).
Persistent neuropsychiatric symptoms after COVID-19: a systematic review and meta-analysis
Authors: Badenoch James B. , Rengasamy Emma R. , Watson Cameron , Jansen Katrin , Chakraborty Stuti , Sundaram Ritika D. , Hafeez Danish , Burchill Ella , Saini Aman , Thomas Lucretia , Cross Benjamin , Hunt Camille K. , Conti Isabella , Ralovska Sylvia , Hussain Zain , Butler Matthew , Pollak Thomas A. , Koychev Ivan , Michael Benedict D. , Holling Heinz , Nicholson Timothy R. , Rogers Jonathan P. , Rooney Alasdair G.
Published: December 2021

The nature and extent of persistent neuropsychiatric symptoms after COVID-19 are not established. To help inform mental health service planning in the pandemic recovery phase, we systematically determined the prevalence of neuropsychiatric symptoms in survivors of COVID-19. For this pre-registered systematic review and meta-analysis (PROSPERO ID CRD42021239750), we searched MEDLINE, EMBASE, CINAHL and PsycINFO to 20 February 2021, plus our own curated database. We included peer-reviewed studies reporting neuropsychiatric symptoms at post-acute or later time-points after COVID-19 infection and in control groups where available. For each study, a minimum of two authors extracted summary data. For each symptom, we calculated a pooled prevalence using generalized linear mixed models. Heterogeneity was measured with I2. Subgroup analyses were conducted for COVID-19 hospitalization, severity and duration of follow-up. From 2844 unique titles, we included 51 studies (n = 18 917 patients). The mean duration of follow-up after COVID-19 was 77 days (range 14–182 days). Study quality was most commonly moderate. The most prevalent neuropsychiatric symptom was sleep disturbance [pooled prevalence = 27.4% (95% confidence interval 21.4–34.4%)], followed by fatigue [24.4% (17.5–32.9%)], objective cognitive impairment [20.2% (10.3–35.7%)], anxiety [19.1% (13.3–26.8%)] and post-traumatic stress [15.7% (9.9–24.1%)]. Only two studies reported symptoms in control groups, both reporting higher frequencies in COVID-19 survivors versus controls. Between-study heterogeneity was high (I2 = 79.6–98.6%). There was little or no evidence of differential symptom prevalence based on hospitalization status, severity or follow-up duration. Neuropsychiatric symptoms are common and persistent after recovery from COVID-19. The literature on longer-term consequences is still maturing but indicates a particularly high prevalence of insomnia, fatigue, cognitive impairment and anxiety disorders in the first 6 months after infection.
User Experience (UX) Design as a co-design methodology: lessons learned during the development of a web-based portal for cardiac rehabilitation
Authors: Nesbitt Katie , Beleigoli Alline , Du Huiyun , Tirimacco Rosy , Clark Robyn A
Published: December 2021

Person-centred care advocates for co-design of all healthcare services and research interventions by the end-user. Co-design is widely used, but the methodological approaches, evaluation, and reporting of outcomes are often poorly defined. One methodology for co-design is the User Experience Design which provides guidance and theoretical frameworks to inform development and reporting measures. This article outlines the application of this approach in the development of a web-based cardiac rehabilitation program and reports on the very positive experiences of the patients involved in the process and how their input strategically influenced outcomes.
Radical and/or respectable: coverage of radical politics in The Times and the Manchester Guardian in interwar Britain
Authors: Ackerley Aaron
Published: December 2021

A major issue for campaigners for radical political programmes is the question of publicity. A vibrant literature has emerged examining the ways in which the Labour party developed a media strategy and cultivated their own newspapers and links with established media organizations in mid twentieth-century Britain. However, the role of the quality press in helping make the radical respectable in the interwar and Second World War period merits more attention. This article provides a detailed analysis of internal developments at The Times and the Manchester Guardian to explain how both papers came to promote radical policies.
Genetic architecture of microRNA expression and its link to complex diseases in the Japanese population
Authors: Sonehara Kyuto , Sakaue Saori , Maeda Yuichi , Hirata Jun , Kishikawa Toshihiro , Yamamoto Kenichi , Matsuoka Hidetoshi , Yoshimura Maiko , Nii Takuro , Ohshima Shiro , Kumanogoh Atsushi , Okada Yukinori
Published: December 2021

Understanding the genetic effects on non-coding RNA (ncRNA) expression facilitates functional characterization of disease-associated genetic loci. Among several classes of ncRNAs, microRNAs (miRNAs) are key post-transcriptional gene regulators. Despite its biological importance, previous studies on the genetic architecture of miRNA expression focused mostly on the European individuals, underrepresented in other populations. Here, we mapped miRNA expression quantitative trait loci (miRNA-eQTL) for 343 miRNAs in 141 Japanese using small RNA sequencing and whole-genome sequencing, identifying 1275 cis-miRNA-eQTL variants for 40 miRNAs (false discovery rate < 0.2). Of these, 25 miRNAs having eQTL were unreported in the European studies, including 5 miRNAs with their lead variant monomorphic in the European populations, which demonstrates the value of miRNA-eQTL analysis in diverse ancestral populations. MiRNAs with eQTL effect showed allele-specific expression (ASE; e.g. miR-146a-3p), and ASE analysis further detected cis-regulatory variants not captured by the conventional miRNA-eQTL mapping (e.g. miR-933). We identified a copy number variation associated with miRNA expression (e.g. miR-570-3p, P = 7.2 × 10−6), which contributes to a more comprehensive landscape of miRNA-eQTLs. To elucidate a post-transcriptional modification in miRNAs, we created a catalog of miRNA-editing sites, including 10 canonical and 6 non-canonical sites. Finally, by integrating the miRNA-eQTLs and Japanese genome-wide association studies of 25 complex traits (mean n = 192 833), we conducted a transcriptome-wide association study, identifying miR-1908-5p as a potential mediator for adult height, colorectal cancer and type 2 diabetes (P < 9.1 × 10−5). Our study broadens the population diversity in ncRNA-eQTL studies and contributes to functional annotation of disease-associated loci found in non-European populations.
Relative growth and reproductive biology of females of Macrobrachium amazonicum (Heller, 1862) (Decapoda: Caridea: Palaemonidae) in the semiarid Northeast Region, Brazil
Authors: Ventura Emerson , Winick-Silva Allysson , Shinozaki-Mendes Renata A
Published: December 2021

We analyzed aspects related to the relative growth and reproduction of females of Macrobrachium amazonicum (Heller, 1862) in a population of the semiarid Northeast Region of Brazil. Carapace (CL) and total length (TL) ranged 5.57–17.61 mm (mean 10.96 ± 2.07 mm) and 28.96–80.63 mm (mean 52.14 ± 9.13 mm), respectively. Relative growth analysis showed that total length increased in a higher proportion than carapace region (positive allometry). This region also increased in a higher proportion regarding weight (negative allometry) due to energy cost in reproduction. Of the three criteria used to determine size at the onset of maturity (SOM), the smallest size observed was obtained by physiological SOM I (based on advanced vitellogenesis): 8.22 mm CL, followed by functional SOM II (8.83 mm CL, based on ovigerous females) and physiological SOM III (9.48 mm, based on CL50). SOM was influenced by the population’s phenotype, and SOM I and SOM II showed synchronicity. The estimated maximum fecundity was 2,805 eggs per female, with a mean value of 690 eggs. There was continuous reproduction and the dry season favored the percentage occurrence of ovigerous females (September-December 2016 and July-August 2017). The smaller lengths of the individuals, compared to other female populations, were due to the characteristics of the environment and the intrinsic traits of the studied population. The negative allometry for the length-weight relation and the continuous reproductive period with seasonal variation was similar as that recorded for other Brazilian localities. This suggests that these last characteristics are a pattern for this species, which shows a latitudinal variation only in the sizes reached. The fast maturation and continuous reproduction of M. amazonicum females make them a potential species for commercial exploitation.
Calcified amorphous tumor located on a severely calcified mitral annulus in a patient with normal renal function
Authors: Ushioda Ryohei , Shirasaka Tomonori , Kikuchi Shinsuke , Kamiya Hiroyuki , Kanamori Taro
Published: December 2021

A calcified amorphous tumor (CAT) of the heart is a rare, nonneoplastic, intracavitary cardiac mass. Histological examination shows that it contains calcified and amorphous fibrous material with underlying chronic inflammation. Surgical excision is generally recommended to avoid future embolism. The risk of embolism has been reported to be especially high in mitral-annular-calcification-related CAT, which constitutes a subgroup of CAT that is often associated with end-stage renal disease. A case of a CAT attached to the anterior annulus of the mitral valve that was easily removed with a light touch of the forceps through aortotomy is reported.
Long-term safety and effectiveness of abatacept in Japanese patients with rheumatoid arthritis: 3-year follow-up of a postmarketing surveillance
Authors: Harigai Masayoshi , Tsuritani Katsuki , Yoshizawa Yuri , Atsumi Tatsuya , Tanaka Yoshiya
Published: December 2021

Objectives

To analyse the long-term safety and effectiveness of abatacept for rheumatoid arthritis using real-world, Japanese, postmarketing surveillance data, focusing on serious infections and malignancies as priority events.

Methods

This 3-year, multicentre surveillance registered patients undergoing abatacept treatment by intravenous infusion between July 2011 and October 2012.

Results

The safety and effectiveness analysis sets included 647 and 596 patients, respectively. The total observation period for the safety analysis was 1280 patient-years. Over the 3-year follow-up, the incidence rates of adverse drug reactions (ADRs) and serious ADRs were 19.92 per 100 patient-years (22.87% of patients) and 4.06 per 100 patient-years (6.65% of patients), respectively. Infections and infestations were the most common ADRs (14.68%), followed by respiratory, thoracic, and mediastinal disorders (3.09%). Incidence rates of serious infections as ADRs and malignancy as adverse events were 1.95 and 1.02 per 100 patient-years, respectively. Retention rates at 1 and 3 years were 67.4% and 43.9%, respectively. Significant decreases from baseline were observed in Disease Activity Score (DAS) 28-erythrocyte sedimentation rate and DAS28-C-reactive protein, as well as Health Assessment Questionnaire-Disability Index (HAQ-DI) and modified HAQ scores.

Conclusions

No new safety signals were detected during the 3-year observation period and effectiveness was maintained over time.
Dietary nitrate and nitrite and human health: a narrative review by intake source
Authors: Kotopoulou Sotiria , Zampelas Antonis , Magriplis Emmanuella
Published: December 2021

Nitrate and nitrite are plant nutrients that, although ubiquitous in plant foods, are highly controversial substances in human nutrition because they are also used as additives in processed foods and may be found as contaminants in drinking water. The aim for this narrative review is to provide a thorough insight into the current literature on the relationship between dietary nitrate and nitrite and the health risks and benefits by source of intake. The results highlight beneficial effects of nitrate and nitrite consumption from plant origin on cardiovascular disease and, to date, no positive correlation has been reported with cancer. On the contrary, high intake of these compounds from processed animal-based foods is related to an increased risk of gastro-intestinal cancer. Nitrate in drinking water also raises some concern, because it appears to be related to adverse health effects. The up-to-date debate on the role of nitrate and nitrite in human nutrition seems to be justified and more research is required to verify safe consumption.
Risk Factors for CMV Viremia and Treatment-Associated Adverse Events Among Pediatric Hematopoietic Stem Cell Transplant Recipients
Authors: Heston Sarah M , Young Rebecca R , Tanaka John S , Jenkins Kirsten , Vinesett Richard , Saccoccio Frances M , Martin Paul L , Chao Nelson J , Kelly Matthew S
Published: December 2021

Background

Cytomegalovirus (CMV) causes substantial morbidity and mortality after hematopoietic stem cell transplantation (HSCT). There are limited data on risk factors for CMV viremia and the safety of antiviral medications used to treat CMV in children.

Methods

We conducted a single-center retrospective study of children who underwent HSCT between 2000 and 2016. We used log-logistic regression to evaluate associations between clinical characteristics and CMV-free survival at 100 days after HSCT. We compared the incidences of laboratory-defined adverse events (AEs) during treatment with ganciclovir and foscarnet.

Results

Among 969 children, the median (interquartile range) age was 6.5 (3.1–11.5) years, and 80% underwent allogeneic HSCT. Two hundred forty-four (25%) children developed CMV viremia. Older age (odds ratio [OR], 0.95; 95% CI, 0.92–0.98), male sex (OR, 0.71; 95% CI, 0.51–0.99), non-Black, non-White race (OR, 0.56; 95% CI, 0.36–0.87), umbilical cord blood donor source (OR, 0.28; 95% CI, 0.08–0.97), and CMV seropositivity (R-/D+: OR, 0.17; 95% CI, 0.07–0.41; R+/D-: OR, 0.14; 95% CI, 0.09–0.21; R+/D+: OR, 0.08; 95% CI, 0.04–0.15) were associated with lower odds of 100-day CMV-free survival. Compared with foscarnet, ganciclovir was associated with lower incidences of thrombocytopenia (incidence rate ratio [IRR], 0.38; 95% CI, 0.15–0.97), electrolyte AEs (IRR, 0.42; 95% CI, 0.24–0.75), endocrine AEs (IRR, 0.52; 95% CI, 0.34–0.79), and renal AEs (IRR, 0.36; 95% CI, 0.19–0.65).

Conclusions

CMV viremia occurred commonly among children after HSCT, and ganciclovir and foscarnet were associated with distinct toxicity profiles among children with CMV infection. These findings should be considered when developing CMV prevention and treatment strategies for children after HSCT.
The Psychology of Status Competitions within Organizations: Navigating Two Competing Motives
Authors: Doyle Sarah P. , Kim Sijun , Young Kim Hee
Published: December 2021

Status hierarchies, which represent how individuals stack up based on the amount of influence and respect they have relative to others, develop quickly as group members make judgments and inferences about others’ competencies or expected contributions to the group. While quick to emerge, one’s place in the hierarchy is not entirely fixed. Because occupying higher status offers a number of rewards and benefits, people vie with others to achieve the higher status positions, and seek to maintain them by engaging in behaviors that have downstream effects on group and individual outcomes. Scholars have directed increasing attention to the unique psychology associated with status seeking to understand the consequences of hierarchical competitions. This emerging body of work highlights the dual concerns (i.e., self-oriented and other-oriented concerns) inherent in the pursuit of status and offers new insights to aid our understanding of status competitions. In this chapter, the authors first review the literature that explores the mixed-motive psychology of status striving, noting the potentially beneficial and destructive behavioral outcomes that status competitions can elicit within workgroups. Next, the authors detail some of the structural, temporal, relational, and individual properties that may exacerbate people’s self-interested status concerns. The chapter concludes by discussing some of the organizational implications of this body of work and reviewing potentially rich opportunities for future research on status competitions.
Disability and Precarious Work
Authors: Schur Lisa , Kruse Douglas L.
Published: December 2021

This chapter examines the prevalence, causes, and consequences of precarious work among people with disabilities. New US evidence from the government’s Current Population Survey, and reviews of prior studies, show that workers with disabilities are more likely than those without disabilities to be in precarious jobs. This is explained in part by many people with disabilities choosing precarious jobs due to the flexibility these jobs can provide. Other people with disabilities, however, face prejudice and discrimination in obtaining standard jobs and must resort to taking precarious jobs with less security, lower pay and benefits, little or no training and opportunities for advancement, and few, if any, worker protections. Workers with disabilities tend to have worse outcomes on these measures than workers without disabilities in every type of employment arrangement. The disability pay gap is higher in precarious jobs than in full-time permanent jobs. The mixed evidence suggests that precarious jobs create good employment outcomes for some workers with disabilities but bad outcomes for others. While continued efforts are needed to decrease barriers to traditional employment for people with disabilities, efforts are also needed to bring higher pay and greater legal protections to precarious workers, which would especially benefit workers with disabilities.
Administrative Justice and Globalisation
Authors: della Cananea Giacinto
Published: December 2021

This chapter, a discussion of administrative justice beyond the borders of the states, has three related objectives. The first is to point out the growth of this dimension of administrative justice, either within regional organizations or within global regulatory regimes. The second is to examine the challenges facing the new institutions and the commonalities and differences between their foundations, particularly with regard to the general principles of law aiming at promoting sound governance, such as due process, impartiality, and proportionality. The third objective is to examine the role of law. Judicial review and judicial doctrines are part of the story, but are not the whole story. It will be seen that law, both hard and soft, plays several roles in this area and variably impinges on the interest at stake.
Exploring the Role of Enforcement in Promoting Adherence with Protective Behaviours during COVID-19
Authors: Mills Freya , Symons Charles , Carter Holly
Published: December 2021

The aim of this narrative review was to explore the conditions under which enforcement likely is, or is not, an effective strategy to increase adherence to recommended protective behaviours during COVID-19. Relevant search terms were entered into four key databases (Google, Google Scholar, medXriv, and psyArXiv) to identify both academic and non-academic papers relating to the use of enforcement. Primary research, reviews, blogs, newspaper reports, and theoretical descriptions were included. This review suggests that enforcement is less effective when: it is applied inconsistently; rules are ambiguous; and behaviours are unobservable. Providing food and financial support, creating social norms, and increasing trust are more effective in addressing specific barriers and fostering voluntary adherence. Where enforcement forms part of the strategy for policing COVID-19 regulations, rules must be clear and local responders must be given time and opportunity to plan their response as new rules are implemented. Due to the narrative nature of the review, and the rapidly changing nature of the COVID-19 pandemic, some evidence may have been inadvertently excluded. Findings inform an understanding of the impact of the public narrative of enforcement on adherence and facilitate the development of recommendations for increasing adherence to protective behaviours during COVID-19. Given the importance of public adherence, these recommendations are not only useful in the context of COVID-19 but also for future public health emergencies. This narrative review is the first to explore the circumstances under which enforcement can increase or reduce adherence with COVID-19 guidelines, generating recommendations for improved public adherence.
High Levels of Self-Reported Depressive Symptoms Among Physical Therapists and Physical Therapist Students Are Associated With Musculoskeletal Pain: A Cross-Sectional Study
Authors: Yona Tomer , Weisman Asaf , Gottlieb Uri , Masharawi Youssef
Published: December 2021

Objective

Depressive symptoms and musculoskeletal (MSK) pain are 2 of the most common health conditions. Their relationship, however, remains unclear. As depressive symptoms in physical therapists have not been well assessed, the purpose of this work was to assess self-reported depressive symptoms and MSK pain prevalence—and their possible association—in physical therapists and physical therapist students.

Methods

An online cross-sectional survey was used to gather data from 707 physical therapists and 116 physical therapist students from Israel. The Patient Health Questionnaire-9 was used to assess depressive symptoms, and the Extended Nordic Musculoskeletal Questionnaire was used to evaluate the prevalence and characteristics of MSK pain.

Results

Overall, 108 participants (13.1%) scored in the moderate to severe depressive symptoms category (Patient Health Questionnaire-9 score >10), and 261 participants (31.7%) scored in the mild depressive symptoms category. In total, 84 physical therapists (11.9%) and 24 physical therapist students (20.7%) reported moderate to severe depressive symptoms during the last 2 weeks. Neck and back pain had the highest point prevalence (26.7%–35.3%) and lifetime prevalence (75.9%–78.5%), respectively. Mild depressive symptoms were associated with current pain (adjusted odds ratio [OR] = 1.58) and smoking (adjusted OR = 1.79–1.84). Current pain was also associated with severe depressive symptoms (adjusted OR = 2.76–3.07). Physical therapists with higher salaries were less likely to report severe depressive symptoms (adjusted OR = 0.11–0.36).

Conclusion

The prevalence estimates generated from this study sample imply that 11.9% of physical therapists and 20.7% of physical therapist students in Israel experienced moderate to severe depressive symptoms. Neck and back pain had the highest point and lifetime prevalence.

Impact

The prevalence of self-reported depressive symptoms in this sample places physical therapists and physical therapist students alongside physicians, nurses, and medical profession students who have been previously reported to have elevated depressive symptoms. Future studies should further explore the nature of the association between pain and depressive symptoms in these populations.
Validation of the Southend giant cell arteritis probability score in a Scottish single-centre fast-track pathway
Authors: Melville Andrew R , Donaldson Karen , Dale James , Ciechomska Anna
Published: December 2021

Objective

The aim was to provide external validation of the Southend GCA probability score (GCAPS) in patients attending a GCA fast-track pathway (GCA FTP) in NHS Lanarkshire.

Methods

Consecutive GCA FTP patients between November 2018 and December 2020 underwent GCAPS assessment as part of routine care. GCA diagnoses were supported by US of the cranial and axillary arteries (USS), with or without temporal artery biopsy (TAB), and confirmed at 6 months. Percentages of patients with GCA according to GCAPS risk group, performance of total GCAPS in distinguishing GCA/non-GCA final diagnoses, and test characteristics using different GCAPS binary cut-offs were assessed. Associations between individual GCAPS components and GCA and the value of USS and TAB in the diagnostic process were also explored.

Results

Forty-four of 129 patients were diagnosed with GCA, including 0 of 41 GCAPS low-risk patients (GCAPS <9), 3 of 40 medium-risk patients (GCAPS 9–12) and 41 of 48 high-risk patients (GCAPS >12). Overall performance of GCAPS in distinguishing GCA/non-GCA was excellent [area under the receiver operating characteristic curve, 0.976 (95% CI 0.954, 0.999)]. GCAPS cut-off ≥10 had 100.0% sensitivity and 67.1% specificity for GCA. GCAPS cut-off ≥13 had the highest accuracy (91.5%), with 93.2% sensitivity and 90.6% specificity. Several individual GCAPS components were associated with GCA. Sensitivity of USS increased by ascending GCAPS risk group (nil, 33.3% and 90.2%, respectively). TAB was diagnostically useful in cases where USS was inconclusive.

Conclusion

This is the first published study to describe application of GCAPS outside the specialist centre where it was developed. Performance of GCAPS as a risk stratification tool was excellent. GCAPS might have additional value for screening GCA FTP referrals and guiding empirical glucocorticoid treatment.
Genetic Diversity and Aggressiveness of Fusarium virguliforme Isolates Across the Midwestern United States
Authors: Olarte Rodrigo A. , Hall Rebecca , Tabima Javier F. , Malvick Dean , Bushley Kathryn
Published: December 2021

Sudden death syndrome (SDS) of soybean is a damaging disease caused by the fungus Fusarium virguliforme. Since this pathogen was first reported in the southern U.S. state of Arkansas in 1971, it has spread throughout the midwestern United States. The SDS pathogen primarily colonizes roots but also produces toxins that translocate to and damage leaves. Previous studies have detected little to no genetic differentiation among isolates, suggesting F. virguliforme in North America has limited genetic diversity and a clonal population structure. Yet, isolates vary in virulence to roots and leaves. We characterized a set of F. virguliforme isolates from the midwestern United States, representing a south to north latitudinal gradient from Arkansas to Minnesota. Ten previously tested microsatellite loci were used to genotype isolates, and plant assays were conducted to assess virulence. Three distinct population clusters were differentiated across isolates. Although isolates ranged in virulence classes from low to very high, little correlation was found between virulence phenotype and cluster membership. Similarly, population structure and geographic location were not highly correlated. However, the earliest diverging cluster had the lowest genetic diversity and was detected only in southern states, whereas the two other clusters were distributed across the Midwest and were predominant in Minnesota. One of the midwestern clusters had the greatest genetic diversity and was found along the northern edge of the known distribution. The results support three genetically distinct population clusters of F. virguliforme in the United States, with two clusters contributing most to spread of this fungus across the Midwest.
Diagnosing and managing acute abdominal pain in children
Authors: Raymond Monique , Marsicovetere Priscilla , DeShaney Katrina
Published: December 2021

Acute abdominal pain is a common complaint in children. The care of these patients is challenging for clinicians because presentation, diagnosis, and treatment are different in children than adults. This article describes the presentation, physical examination, diagnosis, and treatment of common causes of acute abdominal pain in children and discusses emerging trends in diagnosis and treatment.
Different Response to Immunotherapy According to Melanoma Histologic Subtype
Authors: Pala Laura , Conforti Fabio , Pagan Eleonora , Bagnardi Vincenzo , De Pas Tommaso M. , Mazzarol Giovanni , Barberis Massimo , Pennacchioli Elisabetta , Orsolini Gianmarco , Prestianni Pierpaolo , Zagami Paola , Nicolo’ Eleonora , Patanè Damiano , Saponara Maristella , Queirolo Paola
Published: December 2021

Superficial spreading melanoma (SSM) and nodular melanoma (NM) are the most common melanoma histologic subtypes and are characterized by different biological features. We retrospectively analyzed all consecutive patients with advanced melanoma, treated with anti-PD-1 and/or anti-CTLA-4 at our center, with data available on primary tumor subtype. The primary objective was to assess the association between histologic subtype and patients’ outcomes. In addition, we analyzed whole-exome and whole-transcriptome sequencing data of a cohort of advanced melanoma to identify genes and related pathways, characterized by significant differences between NMs and SSMs. Twenty-one patients with NM and 39 with SSM, treated with anti-PD-1(53/60) as monotherapy or combined with anti-CTLA-4 (7/60), were analyzed. All known clinical-pathologic prognostic factors were well balanced between NM and SSM groups, except for the ECOG-PS score. The overall response rate was 52.4% (95% confidence interval, 29.8–74.3) in the NMs group versus 20.5% (9.3–36.5) in the SSMs group (P-value=0.02). The median progression-free survival and overall survival were, respectively, 13.9 and 44.5 months in the NMs group versus only 3.2 and 12 months in SSMs group (progression-free survival P-value=0.032; overall survival P-value=0.002). Multivariable analysis adjusting for the ECOG-PS, confirmed similar results. Whole-exome and whole-transcriptome data of 28 NMs and 21 SSMs were analyzed. No significant differences were observed in terms of both TMB and frequency of mutation in any gene. A total of 266 genes were overexpressed in NMs as compared with SSMs, and enrichment-analysis revealed a significant enrichment (false discovery rate<0.05) of genes belonging to immune-related pathways involved in antigens presentation mechanisms, response to interferon gamma and neutrophil activation. We provided clinical evidences suggesting a relevant association between melanoma histologic subtype and response to immunotherapy.
Reinfection rates among patients previously infected by SARS-CoV-2: systematic review and meta-analysis
Authors: Mao Yinjun , Wang Weiwei , Ma Jun , Wu Shanshan , Sun Feng
Published: December 2021

Background:

Asymptomatic or symptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be followed by reinfection. The protection conferred by prior infection among coronavirus disease 2019 (COVID-19) patients is unclear. We assessed the incidence of SARS-CoV-2 reinfection and the protection effect of previous infection against reinfection.

Methods:

We searched PubMed, EMBASE, Cochrane, Scopus, Web of Science, and ClinicalTrials.gov for publications up until the end date of May 1, 2021. The reinfection rate of recovered patients and the protection against reinfection were analyzed using meta-analysis.

Results:

Overall, 19 studies of 1096 reinfection patients were included. The pooled reinfection rate was 0.65% (95% confidence interval [CI] 0.39–0.98%). The symptomatic reinfection rate was a bit lower (0.37% [95% CI 0.11–0.78%], I
2 = 99%). The reinfection rate was much higher in high-risk populations (1.59% [95% CI 0.30–3.88%], I
2 = 90%). The protection against reinfection and symptomatic reinfection was similar (87.02% [95% CI 83.22–89.96%] and 87.17% [95% CI 83.09–90.26%], respectively).

Conclusions:

The rate of reinfection with SARS-CoV-2 is relatively low. The protection against SARS-CoV-2 after natural infection is comparable to that estimated for vaccine efficacy. These data may help guide public health measures and vaccination strategies in response to the COVID-19 pandemic. High-quality clinical studies are needed to establish the relevant risk factors in recovered patients.
Isobolographic analysis of antinociceptive effect of ketorolac, indomethacin, and paracetamol after simultaneous peripheral local and systemic administration
Authors: Martínez-Martínez Mayra del Carmen , Parra-Flores Leonor Ivonne , Baeza-Flores Guadalupe del Carmen , Torres-López Jorge Elías
Published: December 2021

This study was designed to characterize the type of interaction (subadditive, additive, or synergistic) after simultaneous administration by two different routes (intraperitoneal plus peripheral local) of the same nonsteroidal anti-inflammatory drugs (NSAID) ketorolac and indomethacin or paracetamol. The antinociceptive effects of locally or intraperitoneally delivery of NSAIDs or paracetamol, and the simultaneous administration by the two routes at fixed-dose ratio combination were evaluated using the formalin test. Pain-related behavior was quantified as the number of flinches of the injected paw. Isobolographic analysis was used to characterize the interaction between the two routes. ED30 values were estimated for individual drugs, and isobolograms were constructed. Ketorolac, indomethacin, or paracetamol and fixed-dose ratio combinations produced a dose-dependent antinociceptive effect in the second but not in the first phase of the formalin test. The analysis of interaction type after simultaneous administration by the two routes the same NSAID or paracetamol (on basis of their ED30), revealed that the simultaneous administration of ketorolac or paracetamol was additive and for indomethacin was synergistic. Since the mechanisms underlying the additive effect of ketorolac or paracetamol and the synergistic effect of indomethacin were not explored; it is possible that the peripheral and central mechanism is occurring at several anatomical sites. The significance of these findings for theory and pain pharmacotherapy practice indicates that the combination of one analgesic drug given simultaneously by two different administration routes could be an additive or it could lead to a synergistic interaction.
Ocular Surface Squamous Neoplasia Masquerading as Recalcitrant Epithelial Keratitis
Authors: Watane Arjun , Hansen Eric D. , Vazquez Luis E. , Karp Carol L.
Published: December 2021

Purpose:

The purpose of this study was to report a unique case of ocular surface squamous neoplasia that masqueraded as a nonresolving toxic epithelial keratitis.

Methods:

This was a case report and review of the literature.

Results:

A 79-year-old man presented with decreased vision, redness, and a foreign body sensation in his right eye that was refractory to treatment with lubrication and topical nonsteroidal antiinflammatory drops. Before presentation, the referring provider believed that he had medicamentosa-related keratitis and placed him on oral methazolamide. Slitlamp biomicroscopy of the right eye revealed diffuse epitheliopathy with punctate fluorescein staining and subtle underlying corneal epithelial opalescence. A mildly thickened and inflamed pinguecula was noted from 2 to 5 o'clock at the limbus of the right eye. An anterior segment high-resolution optical coherence tomography revealed thickened, hyperreflective epithelium with an abrupt transition. An incisional biopsy confirmed conjunctival and corneal intraepithelial neoplasia. The patient improved after 4 cycles of topical chemotherapy with 1% 5-fluorouracil eye drops with complete resolution of the corneal and conjunctival pathology.

Conclusions:

Ocular surface squamous neoplasia can rarely masquerade as a recalcitrant medicamentosa and epithelial keratitis. In subtle cases or in cases with combined ocular surface morbidities, anterior segment high-resolution optical coherence tomography can be helpful to diagnose and direct therapy.
Laparoscopic duodenum-preserving pancreatic head resection: a narrative review
Authors: Wujimaimaiti Nuerabula , Wu Yi , Yuan Jingxiong , Jin Jikuan , Wang Hebin , Li Shizhen , Zhang Hang , Wang Min , Qin Renyi
Published: December 2021

Pancreatic surgery is one of the most complex and challenging fields in abdominal surgery associated with extensive surgical trauma, damage to adjacent organs, a long operation time and a high incidence of postoperative complications. Since the early 1990s, laparoscopic techniques have been applied to a growing number of pancreas surgeries, and great progress has been achieved in laparoscopic pancreaticoduodenectomy. As surgeons become proficient in laparoscopic pancreaticoduodenectomy techniques, laparoscopic techniques are gradually used in other pancreatic surgeries, such as laparoscopic distal pancreatectomies and laparoscopic duodenum-preserving pancreatic head resection (LDPPHR), which may benefit patients by reducing postoperative pain and hospital stays and providing a quick recovery to normal activity. Recently, a great number of literature have introduced LDPPHR. It is a good surgical method for benign and low-grade malignant tumors of the pancreatic head. Although LDPPHR is technically feasible, it is not yet generally practicable and limited to highly skilled endoscopic surgeons, and the long-term results after LDPPHR are still not well defined. This article aims to provide a literature review of LDPPHR to assess its feasibility, safety, postoperative recovery, and future outlook according to early experiences of this technique.
Stearoyl-CoA desaturase 1 inhibitor supplemented with gemcitabine treatment reduces the viability and fatty acid content of pancreatic cancer cells in vitro
Authors: Hackney Amon B. , Chung Wen Y. , Isherwood John , Dennison Ashley R. , Martin Naomi
Published: December 2021

Objective:

Pancreatic cancer (PC) is an aggressive cancer with ineffective treatment. Inhibition of stearoyl-CoA desaturase 1 (SCD1) suppresses cancer proliferation and might act as a novel chemotherapy supplement, but this has not been investigated in PC. Here, the effects of SCD1 inhibitor CAY10566 supplemented with gemcitabine treatment (gemcitabine+CAY10566) on PC cell viability, apoptosis, phenotype, fatty acid content, platelet-derived growth factor release, and cell size were investigated.

Methods:

Human PC cell line (PANC-1) was treated with SCD1 inhibitor CAY10566 with or without gemcitabine. Cell viability was assayed using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide and apoptosis and phenotype were determined using flow cytometry. Fatty acid content and platelet-derived growth factor release were measured by enzyme-linked immunosorbent assay. Cell size was determined using scanning electron microscopy.

Results:

Half-maximal inhibitory concentration of gemcitabine or CAY10566 significantly reduced PANC-1 viability compared to gemcitabine alone (P < .0001). No significant differences in the phenotype of phosphatidylserine, tissue factor or basigin expression were detected at therapeutic doses (P > .05). Apoptosis was significantly increased following incubation with CAY10566 (P < .05). Fatty acid content of cells was significantly higher following gemcitabine treatment compared to CAY10566 alone or gemcitabine+CAY10566 (P < .05). Platelet-derived growth factor released by gemcitabine-treated cells was significantly increased compared to 142 nM CAY10566 alone or gemcitabine+CAY10566 (P < .01). CAY10566 did not affect the size of isolated tumor cells but gemcitabine+CAY10566 significantly increased the size compared to the control (P < .05). Cell viability decreased significantly after the treatment with gemcitabine+CAY10566 compared with CAY10566 alone (P < .05) and gemcitabine alone (P < .01). However, when cycles of chemotherapy were mimicked and treatment was removed, the number of cell viability was significantly reduced (P < .05).

Conclusion:

This study suggests that CAY10566 may be a suitable supplement for gemcitabine chemotherapy for PC.
Lung microbiome, gut–lung axis and chronic obstructive pulmonary disease
Authors: Gokulan Kuppan , Joshi Manish , Khare Sangeeta , Bartter Thaddeus
Published: December 2021

Purpose of review

To review recent data on the microbiome of the lungs and how it changes with the evolution of COPD. To explore initial data with respect to COPD and the gut–lung axis. An expanded understanding of the pathogenesis of COPD may lead to new therapeutic targets.

Recent findings

Intermittent pulmonary seeding is essential to health. The lung inflammation of chronic obstructive pulmonary disease (COPD) appears to change the lung milieu such that there is a shift in the microbiome of the lung as COPD progresses. Current data contain internal contradictions, but viewed in to suggest that the lung microbiome participates in the ongoing process of inflammation and destruction (in contrast to the role of the ‘healthy lung’ microbiome). Gut and lung ‘communicate’ and share some functions. COPD is associated with increased intestinal permeability (a dysfunction associated with inflammation). COPD has an impact upon the gastrointestinal microbiome. The gastrointestinal tract may, thus play a role in the progression of COPD.

Lung injury/inflammation alters the milieu of the lung and favors an evolving microbiome, which reflects and probably participates in the processes of inflammation and injury. There is some evidence that the gastrointestinal tract participates in that inflammatory process.
Pre-chronic obstructive pulmonary disease: a pathophysiologic process or an opinion term?
Authors: Mkorombindo Takudzwa , Dransfield Mark T.
Published: December 2021

Purpose of review

Current guidelines does not include current or former smokers who do not have spirometric airflow limitation in their diagnostic or therapeutic algorithms for chronic obstructive pulmonary disease (COPD). The purpose of this review is to outline the burden of respiratory morbidity in this population and to discuss the potential utility of their classification as pre-COPD.

Recent findings

It is increasingly clear that patients with a history of exposure to cigarette smoke or other environmental pollutants may have substantial lung pathology and respiratory impairment even in the absence of airflow limitation, as detected by spirometry. Not all of these patients will develop airflow limitation, but many will have considerable respiratory morbidity and a comparable prognosis to those with classical, spirometrically defined COPD. The use of the term pre-COPD may allow for the identification of these individuals in order to target preventive and earlier therapeutic strategies.

Spirometry is not adequately sensitive to identify many current and former smokers and other exposed populations with significant lung pathology and respiratory symptoms. Though the pathologic processes present in these patients differ, the earlier identification of this pre-COPD population may foster the development of more effective and disease-modifying treatments.
Impact of Medicaid Eligibility Changes on Long-acting Reversible Contraception Use in Massachusetts and Maine
Authors: Pace Lydia E. , Saran Indrani , Hawkins Summer Sherburne
Published: December 2021

Background:

Availability of long-acting reversible contraception (LARC) is an important indicator of high-quality women’s health care. There are limited data on the impact of state-level Medicaid eligibility changes on LARC use.

Study Design:

We used All-Payers Claims Databases to examine LARC insertions among women enrolled in Medicaid in Massachusetts, which expanded Medicaid in 2014, and Maine, which restricted Medicaid eligibility in 2013. We used interrupted time series (ITS) analyses to determine the impact of Medicaid eligibility changes on level and trends in LARC insertions in these states.

Results:

In Massachusetts, graphical evidence demonstrates that after Medicaid expansion, there was an immediate increase in mean monthly LARC insertions and insertions per 1000 enrollees. In ITS regression adjusting for age, LARC insertions per enrollee increased immediately after Medicaid expansion by 32% (P<0.001). After expansion, as the number of enrollees continued to rise, mean monthly LARC insertions rose, but there was a slightly decreasing trend in insertions per enrollee by 1% per month (P<0.001). In Maine, graphical evidence shows that initial reductions in Medicaid eligibility were associated with an immediate drop in LARC insertion numbers and rates per 1000, with ITS regression demonstrating an immediate 17% drop in insertions per enrollee (P<0.001). As Maine’s Medicaid enrollment declined from 2013 to 2015, the number of LARC insertions remained flat, leading to an increasing trend in insertions per enrollee, similar to pre-2013 trends (P=0.17).

Conclusions:

Medicaid eligibility changes were associated with immediate changes in LARC uptake. Medicaid expansion may help ensure access to this effective contraceptive method.