bluuebunny/crossref_metadata_2025 huggingface dataset:
Spectroscopic and imaging observations of transient hot and cool loops by IRIS and SDO
Authors: Gupta Girjesh R , Nayak Sushree S
Published: March 2022

Coronal loops are the basic building blocks of the solar atmosphere and are observed on various length scales. However, their formation mechanism is still unclear. In this paper, we present spectroscopic and imaging observations of small-scale transients and the subsequent formation of transient loops. For this purpose, we have utilized the multiwavelength observations recorded by the Atmospheric Imaging Assembly (AIA) and the Interface Region Imaging Spectrograph (IRIS) slit-jaw imager (SJI), along with spectroscopic measurements provided by IRIS. For the photospheric magnetic field data, we obtained line-of-sight magnetogram data provided by the Helioseismic and Magnetic Imager (HMI). Small-scale transients are simultaneously observed with several EUV and UV passbands of AIA and IRIS/SJI. The HMI magnetogram provides evidence of negative flux cancellations beneath these transients. Differential emission measure (DEM) analysis shows that one of the transients attains temperatures up to 8 MK whereas another one only reaches 0.4 MK. These transients further lead to the formation of small-scale loops with similar temperature distributions, thus termed hot and cool loops respectively. During the course of events, the IRIS slit was rastering the region and thus provided spectroscopic measurements at both transients and associated loops. This enabled us to perform in-depth investigations of the hot and cool loops. Using a density-sensitive O iv line pair, we obtained average electron densities along the hot and cool loops to be 1011.2 and 1010.8 cm−3 respectively. Energy estimates suggest that flux cancellation could easily power the hot transient, while it is insufficient for the cool transient. Lifetime estimates and magnetic field extrapolation suggest the presence of small-scale and fine structures within these loops. The results provide crucial ingredients for the physics of loop formation and the thermodynamics involved.
Quantitative Lipidomics and Spatial MS-Imaging Uncovered Neurological and Systemic Lipid Metabolic Pathways Underlying Troglomorphic Adaptations in Cave-Dwelling Fish
Authors: Lam Sin Man , Li Jie , Sun Huan , Mao Weining , Lu Zongmin , Zhao Qingshuo , Han Chao , Gong Xia , Jiang Binhua , Chua Gek Huey , Zhao Zhenwen , Meng Fanwei , Shui Guanghou
Published: March 2022

Sinocyclocheilus represents a rare, freshwater teleost genus endemic to China that comprises the river-dwelling surface fish and the cave-dwelling cavefish. Using a combinatorial approach of quantitative lipidomics and mass-spectrometry imaging (MSI), we demonstrated that neural compartmentalization of lipid distribution and lipid metabolism is associated with the evolution of troglomorphic traits in Sinocyclocheilus. Attenuated docosahexaenoic acid (DHA) biosynthesis via the Δ4 desaturase pathway led to reductions in DHA-phospholipids in cavefish cerebellum. Instead, cavefish accumulates arachidonic acid-phospholipids that may disfavor retinotectal arbor growth. Importantly, MSI of sulfatides coupled with immunostaining of myelin basic protein and transmission electron microscopy images of hindbrain axons revealed demyelination in cavefish raphe serotonergic neurons. Demyelination in cavefish parallels the loss of neuroplasticity governing social behavior such as aggressive dominance. Outside the brain, quantitative lipidomics and qRT-PCR revealed systemic reductions in membrane esterified DHAs in the liver, attributed to suppression of genes along the Sprecher pathway (elovl2, elovl5, and acox1). Development of fatty livers was observed in cavefish; likely mediated by an impeded mobilization of storage lipids, as evident in the diminished expressions of pnpla2, lipea, lipeb, dagla, and mgll; and suppressed β-oxidation of fatty acyls via both mitochondria and peroxisomes as reflected in the reduced expressions of cpt1ab, hadhaa, cpt2, decr1, and acox1. These neurological and systemic metabolic adaptations serve to reduce energy expenditure, forming the basis of recessive evolution that eliminates nonessential morphological and behavioral traits and giving cavefish a selective advantage to thrive in caves where proper resource allocation becomes a major determinant of survival.
Hydrogen-deuterium exchange mass spectrometry of Mtr4 with diverse RNAs reveals substrate-dependent dynamics and interfaces in the arch
Authors: Zhang Naifu , Olsen Keith J , Ball Darby , Johnson Sean J , D’Arcy Sheena
Published: March 2022

Mtr4 is a eukaryotic RNA helicase required for RNA decay by the nuclear exosome. Previous studies have shown how RNA en route to the exosome threads through the highly conserved helicase core of Mtr4. Mtr4 also contains an arch domain, although details of potential interactions between the arch and RNA have been elusive. To understand the interaction of Saccharomyces cerevisiae Mtr4 with various RNAs, we have characterized RNA binding in solution using hydrogen-deuterium exchange mass spectrometry, and affinity and unwinding assays. We have identified RNA interactions within the helicase core that are consistent with existing structures and do not vary between tRNA, single-stranded RNA and double-stranded RNA constructs. We have also identified novel RNA interactions with a region of the arch known as the fist or KOW. These interactions are important for RNA unwinding and vary in strength depending on RNA structure and length. They account for Mtr4 discrimination between different RNAs. These interactions further drive Mtr4 to adopt a closed conformation characterized by reduced dynamics of the arch arm and intra-domain contacts between the fist and helicase core.
The Modified E-Cigarette Evaluation Questionnaire: Psychometric Evaluation of an Adapted Version of the Modified Cigarette Evaluation Questionnaire for Use With Adults Who Use Electronic Nicotine Delivery Systems
Authors: Morean Meghan E , Bold Krysten W
Published: March 2022

Introduction

The subjective experience of positive and negative effects likely contributes to e-cigarette use, and the Modified Cigarette Evaluation Questionnaire (MCEQ) previously has been adapted to assess the reinforcing and aversive effects of vaping. However, the psychometric properties of the MCEQ for use with e-cigarettes have not been established.

Aims and Methods

We examined the psychometric properties of the Modified E-cigarette Evaluation Questionnaire (MECEQ) within a sample of 857 adults who recently used e-cigarettes in a smoking cessation attempt (52.4% male; 40.84 [12.25] years old; 62.8% non-Hispanic white; 22.4% daily e-cigarette users). Analyses included confirmatory factor analysis of the original structure, exploratory/confirmatory factor analyses to identify the alternate latent structure(s), internal consistency, measurement invariance, between-group differences, and test-criterion relationships with vaping-related outcomes.

Results

The original five-factor structure and a novel four-factor structure were supported. Each was scalar invariant across several participant subgroups (eg, current smoking status, daily vaping status). All multi-item subscales were internally consistent. Both versions detected several between-group differences. For example, current smokers reported stronger aversive effects than did exclusive e-cigarette users. Finally, adjusted relationships between both MECEQ versions and vaping-related outcomes provided evidence for concurrent validity.

Conclusions

The five-factor and four-factor versions of the MECEQ evidenced good-to-excellent internal consistency, scalar measurement invariance, and concurrent relationships with vaping-related outcomes. While both versions could be used to assess subjective vaping effects in adults with histories of cigarette smoking and vaping, additional research is needed to evaluate the applicability of these factor structures to other samples (eg, e-cigarette users with no smoking history, youth).

Implications

Although the MCEQ has been adapted in previously published studies to assess the subjective reinforcing and aversive effects of vaping, the psychometric foundation necessary for doing so had not been established. We showed that the MECEQ can be scored using the original five-factor MCEQ format or using a newly identified four-factor structure. Both versions evidenced construct validity, internal consistency, measurement invariance (permitting between-group comparisons), and concurrent validity with vaping-related outcomes. Results strengthen the interpretability of previously published work using the five-factor MCEQ structure and provide an alternative scoring approach for vaping-specific subjective effects.
Economic geography aspects of the Panama Canal
Authors: Maurer Stephan , Rauch Ferdinand
Published: March 2022

This paper studies how the opening of the Panama Canal in 1914 changed counties’ market potential and influenced the economic geography of the USA. We compute shipment effective distances with and without the canal from each US county to each other US county and to international ports and compute the resulting change in market potential. The main elasticity would imply that a 1% increase in market potential led to a total increase of population by around 2.3% in 1940. We compute similar elasticities for wages, land values, and immigration from out of state. Tradable (manufacturing) industries react stronger than non-tradable (services) industries.
Tomato brown rugose fruit virus resistance generated by quadruple knockout of homologs of TOBAMOVIRUS MULTIPLICATION1 in tomato
Authors: Ishikawa Masayuki , Yoshida Tetsuya , Matsuyama Momoko , Kouzai Yusuke , Kano Akihito , Ishibashi Kazuhiro
Published: March 2022

Tomato brown rugose fruit virus (ToBRFV) is an emerging virus of the genus Tobamovirus. ToBRFV overcomes the tobamovirus resistance gene Tm-22 and is rapidly spreading worldwide. Genetic resources for ToBRFV resistance are urgently needed. Here, we show that clustered regularly interspaced short palindromic repeats/CRISPR associated protein 9 (CRISPR/Cas9)-mediated targeted mutagenesis of four tomato (Solanum lycopersicum) homologs of TOBAMOVIRUS MULTIPLICATION1 (TOM1), an Arabidopsis (Arabidopsis thaliana) gene essential for tobamovirus multiplication, confers resistance to ToBRFV in tomato plants. Quadruple-mutant plants did not show detectable ToBRFV coat protein (CP) accumulation or obvious defects in growth or fruit production. When any three of the four TOM1 homologs were disrupted, ToBRFV CP accumulation was detectable but greatly reduced. In the triple mutant, in which ToBRFV CP accumulation was most strongly suppressed, mutant viruses capable of more efficient multiplication in the mutant plants emerged. However, these mutant viruses did not infect the quadruple-mutant plants, suggesting that the resistance of the quadruple-mutant plants is highly durable. The quadruple-mutant plants also showed resistance to three other tobamovirus species. Therefore, tomato plants with strong resistance to tobamoviruses, including ToBRFV, can be generated by CRISPR/Cas9-mediated multiplexed genome editing. The genome-edited plants could facilitate ToBRFV-resistant tomato breeding.
Singmaster’s Conjecture In The Interior Of Pascal’s Triangle
Authors: Matomäki Kaisa , Radziwiłł Maksym , Shao Xuancheng , Tao Terence , Teräväinen Joni
Published: March 2022

Singmaster’s conjecture asserts that every natural number greater than one occurs at most a bounded number of times in Pascal’s triangle; that is, for any natural number $t \geq 2$, the number of solutions to the equation $\binom{n}{m} = t$ for natural numbers $1 \leq m \lt n$ is bounded. In this paper we establish this result in the interior region $\exp(\log^{2/3+\varepsilon} n) \leq m \leq n - \exp(\log^{2/3+\varepsilon} n)$ for any fixed ɛ > 0. Indeed, when t is sufficiently large depending on ɛ, we show that there are at most four solutions (or at most two in either half of Pascal’s triangle) in this region. We also establish analogous results for the equation $(n)_m = t$, where $(n)_m := n(n-1) \dots (n-m+1)$ denotes the falling factorial.
Explicit Estimates for ζ(s) in the Critical Strip Under the Riemann Hypothesis
Authors: Simonič Aleksander
Published: March 2022

Assuming the Riemann Hypothesis, we provide effective upper and lower estimates for $\left|\zeta(s)\right|$ to the right of the critical line. As an application we make explicit Titchmarsh’s conditional bound for the Mertens function and Montgomery–Vaughan’s conditional bound for the number of k-free numbers.
AA amyloidosis complicating cryopyrin-associated periodic syndrome: a study of 86 cases including 23 French patients and systematic review
Authors: Rodrigues François , Cuisset Laurence , Cador-Rousseau Bérangère , Giurgea Irina , Neven Benedicte , Buob David , Quartier Pierre , Hachulla Eric , Lequerré Thierry , Cam Gérard , Boursier Guilaine , Hervieu Valérie , Grateau Gilles , Georgin-Lavialle Sophie
Published: March 2022

Objective

Cryopyrin-associated periodic syndrome (CAPS) is a rare but treatable inherited autoinflammatory condition including familial cold autoinflammatory syndrome (FCAS), Muckle–Wells syndrome (MWS) and chronic infantile neurologic cutaneous articular syndrome (CINCA). Our objective was to describe the main features of CAPS AA amyloidosis (AA-CAPS) associated and the efficacy of IL-1 inhibitors in this indication.

Methods

Retrospective study in France associated with a systematic literature review.

Results

Eighty-six patients were identified: 23 new French cases and 63 from the literature, with a median age at amyloidosis diagnosis of 39 years old. CAPS subtypes were MWS (n = 62), FCAS (n = 9), frontier forms between MWS and FCAS (n = 12) and between CINCA and MWS (n = 3). NLRP3 had been sequenced in 60 patients (70%) and the most frequent mutation was R260W (60%). Three AA-CAPS patients displayed somatic NLRP3 mutations. Death occurred in 35 patients (41%), none of whom having ever received IL-1 inhibitors. Twenty-eight patients (33%) received IL-1 inhibitors, with a >50% decrease in proteinuria in 89% of cases.

Conclusion

AA amyloidosis can occur in nearly all CAPS subtypes. IL-1 inhibitors are effective, underlining the necessity of an early diagnosis of CAPS in order to start this treatment as soon as possible among AA-CAPS patients.
Development and validation of the Kids Disability Screen for children with juvenile idiopathic arthritis: results from the CAPRI Registry
Authors: Houghton Kristin , McPherson Meghan , Surjanovic Nikola , Loughin Thomas , Berard Roberta , Proulx-Gauthier Jean-Phillipe , Chédeville Gaëlle , Rumsey Dax , Schmeling Heinrike , Luca Nadia , Johnson Nicole , Gerschman Tommy , Miettunen Paivi , Tam Herman , Lim Lillian , Morishita Kimberly , Scuccimarri Rosie , Roth Johannes , Duffy Ciaran , Tucker Lori , Feldman Brian M , Guzman Jaime ,   for the CAPRI Registry Investigators, Cabral David , Chédeville Gaëlle , Duffy Ciarán , Gerhold Kerstin , Guzman Jaime , Hiraki Linda , Huber Adam , Schmeling Heinrike , Shiff Natalie , Tucker Lori
Published: March 2022

Objective

The aim of this study was to develop and validate a brief disability screen for children with JIA, the Kids Disability Screen (KDS).

Methods

A total of 216 children enrolled in the Canadian Alliance of Pediatric Rheumatology Investigators (CAPRI) Registry in 2017–2018 formed a development cohort, and 220 children enrolled in 2019–2020 formed a validation cohort. At every clinic visit, parents answered two questions derived from the Childhood Health Assessment Questionnaire (CHAQ): ‘Is it hard for your child to run and play BECAUSE OF ARTHRITIS?’ (‘Hard’ 0–10), and ‘Does your child usually need help from you or another person BECAUSE OF ARTHRITIS?’ (‘Help’, 0–10). We used 36-fold cross-validation and tested nine different mathematical methods to combine the answers and optimize psychometric properties. The results were confirmed in the validation cohort.

Results

Expressed as the mean of the two answers, KDS best balanced ease of use and psychometric properties, while a LASSO regression model combining the two answers with other patient characteristics [estimated CHAQ [eCHAQ]) had the highest responsiveness. In the validation cohort, 22.7%, 25.9% and 28.6% of patients had a score of 0 at enrolment for the KDS, eCHAQ and CHAQ, respectively. Responsiveness was 0.67, 0.74 and 0.62, respectively. Sensitivity to detect a CHAQ > 0 was 0.90 and specificity 0.56, KDS detecting some disability in 44% of children with a CHAQ = 0.

Conclusion

This simple KDS has psychometric properties comparable with those of a full CHAQ and may be used at every clinic visit to identify those children who need a full disability assessment.
LINC01063 functions as an oncogene in melanoma through regulation of miR-5194-mediated SOX12 expression
Authors: Xu Jiangmei , Ou Rongying , Nie Gang , Wen Juan , Ling Li , Mo Laiming , Xu Rui , Lv Mingfen , Zhao Liang , Lai Wei , Xu Yunsheng
Published: March 2022

Melanoma is one of the most aggressive skin cancers and a major cause of cancer-linked deaths worldwide. As the morbidity and mortality of melanoma are increasing, it is necessary to elucidate the potential mechanism influencing melanoma progression. Tumor tissues and adjacent normal tissues (5 cm away from tumors) from 22 melanoma patients at the I–II stage and 39 patients at the III–VI stage were acquired. The expression of LINC01063 in melanoma was estimated by quantitative PCR. Functional assays were employed to investigate the function of LINC01063 in melanoma. Mechanism assays were adopted to explore the mechanism of LINC01063. LINC01063 knockdown impeded melanoma cell proliferation, migration, invasion, and epithelial–mesenchymal transition as well as melanoma tumor growth. Mechanistically, LINC01063 acted as an miR-5194 sponge to upregulate SOX12 expression. Finally, LINC01063 was tested to facilitate the malignant behaviors of melanoma cells via targeting miR-5194/SOX12. LINC01063 was significantly upregulated in melanoma. Specifically, LINC01063 displayed a higher level in patients at an advanced stage or with metastasis than those at an early stage or without metastasis. Our study revealed the oncogenic effects of LINC01063 on melanoma cell/tumor growth and its molecular mechanism involving miR-5194/SOX12, which might support LINC01063 to be the potential prognostic or therapeutic biomarker against melanoma.
Comparison of urinary telomerase, CD44, and NMP22 assays for detection of bladder squamous cell carcinoma
Authors: Al-Delaimy Wael K. , Awadalla Amira , El-Assmy Ahmed , Abol-Enein Hassan , Shokeir Ahmed
Published: March 2022

Background

Squamous cell carcinoma (SCC) of the bladder is common in many regions around the world. Prognosis is very poor, as most cases are diagnosed at an advanced stage due to a lack of affordable and valid screening markers for this type of cancer. The diagnostic accuracy of urinary nuclear matrix protein-22 (NMP22), telomerase activity, and CD44 were evaluated in urine samples of patients with bladder SCC.

Materials and methods

We conducted a case-control study comprised of 60 consecutive newly diagnosed bladder SCC patients diagnosed by cystoscopy and histopathological examination, and controls were 60 outpatients with benign urologic conditions and healthy clinic visitors. Urine samples collected from each subject underwent testing for NMP22, telomerase activity, and CD44. Descriptive and correlational statistical analysis of cases and controls were carried out and receiver operating characteristic curve analysis was used to determine optimal cut-off points for the three assays.

Results

Area under the curve was calculated at 0.96, 0.93, and 0.62 for NMP22, telomerase, and CD44, respectively. Urine levels of NMP22 and telomerase activity were significantly higher in the SCC group compared to controls (p < 0.001). Urine CD44 levels were not significantly higher in the SCC group compared to controls (p = 0.111). The overall sensitivity of NMP22, telomerase, and CD44 was 96.7%, 87%, and 45%, respectively, while the specificity was 85%, 88.6%, and 86.7%, respectively.

Conclusions

Urinary telomerase activity, followed by NMP22 urine levels, showed high diagnostic yield and could hold potential promise as urinary biomarkers for the diagnosis of bladder SCC.
Validation of the Menopause Transition Scale (MTS)
Authors: Andersen Nicholas J. , Parker Jessica L. , Pettigrew Susanne , Bitner Diana
Published: March 2022

Objective

All women will experience menopause transition, and a majority will experience symptoms that negatively affect their quality of life. Current validated menopause symptom scales are time consuming, phrased in clinical language, and difficult to adopt for digital use. This study seeks to validate a short novel survey which can be reliably completed without coaching and accurately represents the experience of the menopause transition.

Methods

We developed a patient-centric questionnaire (Menopause Transition Scale, MTS) to examine for symptoms of menopause. Survey responders represented a total of 144 women with at least one symptom of menopause. Survey responders included women affected by cancer aged 30 to 65 (n = 72) and women not affected by cancer aged 45 to 60 (n = 72). Cronbach Alpha was used to examine for internal consistency and dimensionality was assessed using exploratory factor analysis. The cross-validation was analyzed against established patient scales using Spearman correlations or Chi-Square analysis, as appropriate.

Results

The MTS questions showed internal consistency with a Cronbach Alpha of 0.63. The individual questions loaded into three unique domains. The MTS overall correlated with validated scales for menopause symptoms, the Menopause-Specific Quality of Life Questionnaire (r = –0.86, P < 0.0001) and Greene Climacteric Scale (r = –0.65, P < 0.0001). Libido correlated with scales (P = 0.0150) and subscales (r = –0.70, P < 0.0001) relating low sexual desire. Energy (r = –0.62, P < 0.0001), Mood (r = –0.48, P < 0.0001), and Hot Flashes/Night Sweats (r = –0.77, P < 0.0001) correlated with scales and subscales related to mood, depression, and vasomotor symptoms. The majority of our responders expressed mild vaginal bleeding. The highest frequency of severe symptoms were low libido and poor energy.

Conclusions

The MTS is a short thorough patient-centric survey that is readily amenable to digital adoption to measure symptoms of menopause as women transition in the out-patient setting. Further study is needed for the longitudinal assessment of symptoms through the transition process and the response of women to therapeutic options.

Video Summary: http://links.lww.com/MENO/A938.
Racial/ethnic disparities in the diagnosis and management of menopause symptoms among midlife women veterans
Authors: Blanken Anna , Gibson Carolyn J. , Li Yongmei , Huang Alison J. , Byers Amy L. , Maguen Shira , Inslicht Sabra , Seal Karen
Published: March 2022

Objective

Racial/ethnic disparities in menopause symptoms and hormone therapy management remain understudied among women served by the Veteran’s Health Administration, despite the unique racial/ethnic diversity of this population. Thus, we determined racial/ethnic disparities in medical record-documented menopause symptoms and prescribed menopausal hormone therapy among women veterans.

Methods

We conducted cross-sectional analyses of national Veteran’s Health Administration electronic health record data from 2014 to 2015. We used logistic regression models to compare medical-record documented menopause symptoms and treatment (eg, vaginal estrogen or systemic hormone therapy) by self-identified race/ethnicity, adjusting for age, body mass index, and depression. Models examining hormone treatment were adjusted for menopause symptoms.

Results

Among 200,901 women veterans (mean age 54.3, SD 5.4 y; 58% non-Hispanic/Latinx White, 33% non-Hispanic/Latinx Black, 4% Hispanic/Latinx, and 4% other), 5% had documented menopause symptoms, 5% were prescribed vaginal estrogen, and 5% were prescribed systemic hormone therapy. In fully adjusted multivariable models, non-Hispanic/Latinx Black women veterans had lower odds of documented menopause symptoms relative to non-Hispanic/Latinx White women (OR 0.82, 95% CI: 0.78-0.86). Moreover, non-Hispanic/Latinx Black women (OR 0.74, 95% CI: 0.70-0.77), as well as Hispanic/Latinx women (OR 0.68, 95% CI: 0.61-0.77), had lower likelihood of systemic hormone therapy prescription. Hispanic/Latinx women had higher odds of vaginal estrogen prescription (OR 1.12 95% CI: 1.02-1.24) than non-Hispanic/Latinx White women. Non-Hispanic/Latinx Black women had lower likelihood of estrogen use (OR 0.78 95% CI: 0.74-0.81) than non-Hispanic/Latinx White women.

Conclusion

Despite evidence suggesting higher menopause symptom burden among Black women in community samples, documented menopause symptoms and hormone therapy were less common among Black, compared with White, women veterans. Additionally, Hispanic/Latinx women veterans had lower odds of prescribed systemic menopause therapy and yet higher odds of prescribed vaginal estrogen, despite no difference in documented symptoms. These findings may signal important disparities in symptom reporting, documentation, and/or treatment for minority women veterans.
Overnight orthokeratology-associated Acanthamoeba keratitis at a tertiary referral hospital in Taiwan: A retrospective case-control study
Authors: Hsu Chih-Chien , Kuo Yih-Shiuan , Lin Pei-Yu , Chen Ko-Hua
Published: March 2022

Background:

Acanthamoeba keratitis (AK) is a vision-threatening disease, usually associated with contact lens (CL) wear. As overnight orthokeratology (OOK) is increasingly used to control myopia, we have found incidence of OOK-associated AK is increasing. This study aimed to investigate the clinical presentation and visual outcomes of OOK-associated AK.

Methods:

Demographic characteristics, clinical features, and treatment outcomes were collected by reviewing the medical charts of CL-associated AK patients (n = 35) diagnosed at Taipei Veterans General Hospital from 2001 to 2016. Cases were OOK-associated AK patients (n = 13), and controls were all other CL-associated AK patients (n = 22). Student t tests and chi-square tests were used to compare cases and controls. Linear regression analyses were used to identify factors associated with the final visual outcome in CL-associated AK.

Results:

OOK-associated AK accounted for half of all CL-associated AK after 2010. OOK-associated AK patients and other CL-associated patients had similar best-corrected logarithm of the minimum angle of resolution visual acuity (BCLVA) before treatment (1.10 ± 0.75 vs 1.13 ± 0.76, p = 0.893), but OOK-associated AK patients were younger (17.15 ± 3.21 vs 26.36 ± 12.81 years, p = 0.004), had less severe disease (ring infiltration, 0% vs 31.82%, p = 0.023), and had better post-treatment BCLVA (0.06 ± 0.15 vs 0.51 ± 0.95, p = 0.041). Multiple linear regression analysis showed that better BCLVA after treatment in CL-associated AK was associated with initial presentation without ring infiltration (p = 0.002) but not with OOK use itself (p = 0.793). Twenty-six of 35 CL-associated AK patients had final BCLVA equal to or better than 0.10 (Snellen visual acuity of 6/7.5). All 13 OOK-associated AK cases were treated with chlorhexidine 0.02% ± voriconazole 1% ± oral voriconazole, and 12 of these patients had final BCLVA equal to or better than 0.10.

Conclusion:

Most CL-associated AK patients had satisfactory visual outcomes. Half of AK at our hospital is OOK-associated since 2010. Early diagnosis and correct treatment may be the reason why OOK-associated AK patients had better vision prognosis.
Disease-related malnutrition in chronic kidney disease
Authors: Slee Adrian , Reid Joanne
Published: March 2022

Purpose of review

Disease-related malnutrition has complex and multifactorial pathophysiology. It is common in patients with chronic kidney disease (CKD) and has a devastating impact on morbidity and mortality. Given the rising numbers of patients diagnosed with CKD, disease-related malnutrition is an escalating clinical challenge. This review summarises current knowledge in relation to the development, screening and treatments for disease-related malnutrition in CKD

Recent findings

New research has identified other potential causes for the development of malnutrition in CKD, including changes in taste and smell, and effects of polypharmacy. Screening and assessment studies have investigated different tools in relation to the new Global Leadership Initiative on Malnutrition (GLIM) criteria. Different modalities of low protein diets and the potential use of pre and probiotics are being explored. Furthermore, the importance of nutritional support, and possibly exercise during dialysis is being examined in terms of reducing anabolic resistance and catabolism.

Further research is required to better understand the nuances of the pathophysiology of disease-related malnutrition in CKD. This work should inform not only consistent terminology and the application of assessment tools specific to disease-related malnutrition in CKD but also the development of novel interventions that reflect its multifaceted pathophysiology and impact.
Childhood obesity prevention: what can be achieved?
Authors: Gomahr Julian , Julian Valérie , Thivel David , Maruszczak Katharina , Schneider Anna-Maria , Weghuber Daniel
Published: March 2022

Purpose of review

Childhood obesity is a pandemic generating an enormous individual and socioeconomic burden worldwide. This narrative review summarizes recent evidence on successful and recommended prevention strategies according to age groups and different levels of interventions.

Recent findings

Effective prevention of childhood obesity is feasible and most successful early in life up to preschool age, and it should include a multicomponent approach, integrating individuals, family and society. Trials that improve nutrition and/or enhance physical activity are the cornerstones of childhood obesity prevention on an individual level. However, their efficacy is determined by the combination of interventions for the target age group. Further, improving family support and sleep, as well as reducing screen time, lead to favourable results. Many research gaps remain, including a lack of effective interventions for high-risk groups.

As a multifactorial condition, childhood obesity requires a multicomponent approach. Interventions should be developmental stage-specific and adjusted to the setting. Current research gaps need to be targeted by future trials, with a special focus on the benefit of the most vulnerable groups. From a systems response perspective, a paradigm shift from interventions focusing on the individual to approaches that target society as a whole is warranted.
Paediatric asthma - all that wheezes is not necessarily asthma - current diagnostic and management strategies
Authors: Lecerf Kelsey , Prince Benjamin T.
Published: March 2022

Purpose of review

Asthma is a frequently encountered chronic medical condition encountered in paediatrics, affecting 7% of children under the age of 18 in the United States. Although asthma is one of the more common conditions that is associated with wheezing, there is a broad differential diagnosis to consider. The purpose of this review is to describe other causes of wheezing outside of asthma in a paediatric population and discuss diagnostic and management strategies to consider when evaluating a child or adolescent with wheezing.

Recent findings

The characteristics of the wheezing along with other associated signs and symptoms can be helpful in narrowing the differential diagnosis. The age and the past medical history of the patient are also important aspects to consider when determining next steps in the evaluation and management of paediatric wheezing. In addition to considering other causes of wheezing, it is often necessary to assess for the presence of underlying asthma, and recently updated asthma guidelines from the National Heart, Lung and Blood Institute provide a graded review of various recommendations for making the diagnosis and managing asthma in the clinical setting.

It is important to maintain a broad differential diagnosis when evaluating a paediatric patient with wheezing.
A Practical Approach to Identifying Pediatric Disease‐Associated Undernutrition
Authors: Hulst Jessie M. , Huysentruyt Koen , Gerasimidis Konstantinos , Shamir Raanan , Koletzko Berthold , Chourdakis Michail , Fewtrell Mary , Joosten Koen F. ,   Special Interest Group Clinical Malnutrition of ESPGHAN
Published: March 2022

Disease‐associated undernutrition (DAU) is still common in hospitalized children and is generally accepted to be associated with adverse effects on disease outcomes; hence making proper identification and assessment essential in the management of the sick child. There are however several barriers to routine screening, assessment, and treatment of sick children with poor nutritional status or DAU, including limited resources, lack of nutritional awareness, and lack of agreed nutrition policies. We recommend all pediatric facilities to 1) implement procedures for identification of children with (risk of) DAU, including nutritional screening, criteria for further assessment to establish diagnosis of DAU, and follow‐up, 2) assess weight and height in all children asa minimum, and 3) have the opportunity for children at risk to be assessed by a hospital dietitian. An updated descriptive definition of pediatric DAU is proposed as “Undernutrition is a condition resulting from imbalanced nutrition or abnormal utilization of nutrients which causes clinically meaningful adverse effects on tissue function and/or body size/composition with subsequent impact on health outcomes.” To facilitate comparison of undernutrition data, it is advised that in addition to commonly used criteria for undernutrition such as z score < −2 for weight‐for‐age, weight‐for‐length, or body mass index <−2, an unintentional decline of >1inthese z scores over time should be considered as an indicator requiring further assessment to establish DAU diagnosis. Since the etiology of DAU is multifactorial, clinical evaluation and anthropometry should ideally be complemented by measurements of body composition, assessment of nutritional intake, requirements, and losses, and considering disease specific factors.
The Role of Surgical Management in Chronic Pancreatitis in Children
Authors: Nathan Jaimie D. , Ellery Kate , Balakrishnan Keshawadhana , Bhatt Heli , Ganoza Armando , Husain Sohail Z. , Kumar Rakesh , Morinville Veronique D. , Quiros J. Antonio , Schwarzenberg Sarah J. , Sellers Zachary M. , Uc Aliye , Abu‐El‐Haija Maisam
Published: March 2022

Objectives:

Chronic pancreatitis (CP) is rare in childhood but impactful because of its high disease burden. There is limited literature regarding the management of CP in children, specifically about the various surgical approaches. Herein, we summarize the current pediatric and adult literature and provide recommendations for the surgical management of CP in children.

Methods:

The literature review was performed to include the scope of the problem, indications for operation, conventional surgical options as well as total pancreatectomy with islet autotransplantation, and outcomes following operations for CP.

Results:

Surgery is indicated for children with debilitating CP who have failed maximal medical and endoscopic interventions. Surgical management must be tailored to the patient's unique needs, considering the anatomy and morphology of their disease. A conventional surgical approach (eg, drainage operation, partial resection, combination drainage‐resection) may be considered in the presence of significant and uniform pancreatic duct dilation or an inflammatory head mass. Total pancreatectomy with islet autotransplantation is the best surgical option in patients with small duct disease. The presence of genetic risk factors often portends a suboptimal outcome following a conventional operation.

Conclusions:

The morphology of disease and the presence of genetic risk factors must be considered while determining the optimal surgical approach for children with CP. Surgical outcomes for CP are variable and depend on the type of intervention. A multidisciplinary team approach is needed to assure that the best possible operation is selected for each patient, their recovery is optimized, and their immediate and long‐term postoperative needs are well‐met.
Prevalence and Clinical Significance of Helicobacter Pylori‐negative Chronic Gastritis in Children
Authors: Virkkula Anni , Kivela Laura , Hiltunen Pauliina , Sotka Antti , Huhtala Heini , Kurppa Kalle , Repo Marleena
Published: March 2022

Objectives:

The clinical significance of Helicobacter pylori‐negative chronic gastritis (HPNCG) in children is unclear. We examined this issue in patients who had undergone esophagogastroduodenoscopy with systematic gastric sampling.

Methods:

Data of 1178 consecutive children who underwent diagnostic esophagogastroduodenoscopy were collected. Baseline characteristics and long‐term outcomes were compared between children with active and inactive HPNCG and those with normal gastric histology. Follow‐up data were available for up to 13 years.

Results:

Altogether 24 (2.0%) children had active and 235 (19.9%) inactive HPNCG, 27 (2.3%) were Hpylori‐positive, 46 (3.9%) had other gastric pathology, and 846 (71.8%) normal histology. Diarrhea (31.3% vs 25.1%, P = 0.033), poor growth (23.6% vs 14.7%, P < 0.001), bloody stools (13.9% vs 7.2%, P < 0.001), anemia (46.5% vs 23.4%, P < 0.001), hypersedimentation (39.7% vs 21.4%, P < 0.001), hypoalbuminemia (40.4% vs 16.2%, P < 0.001), and elevated fecal calprotectin (62.4% vs 31.5%, P < 0.001) were more common and heartburn (13.9% vs 22.9%, P = 0.002) less common in the HPNCG group than in the controls. Both active (OR 3.64,95% CI 1.35–9.82) andinactive (2.98, 2.18–4.08) HPNCG predicted a diagnosis in the initial investigations. Crohn disease (41.7%) was the most common diagnosis in active HPNCG and celiac disease (37.4%) in inactive HPNCG. During follow‐up, 7 (9.9%) of the 71 initially nondiagnosed HPNCG children received a diagnosis.

Conclusions:

HPNCG is a frequent finding in children undergoing EGD, the active form being associated especially with Crohn disease and the inactive with celiac disease. The long‐term prognosis of patients with HPNCG who do not receive an initial diagnosis is good.
Expression of IL‐37 Correlates With Immune Cell Infiltrate and Fibrosis in Pediatric Autoimmune Liver Diseases
Authors: Griessmair Lucas , Pirringer Laura , Mountford Steffeni , Sendelhofert Andrea , Makeschin Marie‐Christine , Koletzko Sibylle , Mayr Doris , Bufler Philip
Published: March 2022

Objectives:

The activation of innate immune mechanisms is key for chronic liver injury. Interleukin‐37 (IL‐37) is a profound inhibitor of innate and adaptive immune responses, and its overexpression protects mice from liver inflammation and fibrosis. Here, we characterize the hepatic inflammatory infiltrate and expression of IL‐37 in children with autoimmune liver diseases.

Methods:

We compared the inflammatory microenvironment of the liver in a retrospective cohort of children with primary sclerosing cholangitis (PSC), autoimmune sclerosing cholangitis (ASC) and autoimmune hepatitis (AIH) by immunohistochemistry. The expression of IL‐37 was quantified in liver parenchyma and portal tracts. Double immunofluorescence was used for detection of IL‐37 in specific cell types and colocalization with Smad3.

Results:

AIH is characterized by a dense lymphoplasmacytic infiltrate whereas ASC shows high numbers of granulocytes in portal tracts. IL‐37 expression correlates positively with liver inflammation and fibrosis, the number of infiltrating immune cells and serum markers for hepatic inflammation. IL‐37 is mainly expressed in hepatocytes, cholangiocytes and infiltrating immune cells. Double staining revealed IL‐37 positivity in T helper and regulatory T cells (Treg), Kupffer (KC) and hepatic stellate cells (HSC). IL‐37 colocalizes with intranuclear pSmad3L in areas of liver inflammation.

Conclusions:

Pediatric ASC separates from PSC and AIH by a granulocyte‐rich portal infiltrate. Upregulation of IL‐37 with liver injury, the expression in Treg as well as KC and HSC and the colocalization of IL‐37 with pSmad3L in cholangiocytes and hepatocytes suggest a modulating role to limit hepatic inflammation and fibrosis in pediatric autoimmune liver diseases.
Laparo‐Endoscopic Rendez‐Vous in the Treatment of Cholecysto‐Choledocolithiasis in the Pediatric Population
Authors: Cisarò Fabio , Pane Alessandro , Scottoni Federico , Pizzol Antonio , Romagnoli Renato , Calvo Pier Luigi , Reggio Dario , Gennari Fabrizio
Published: March 2022

Objectives:

The incidence of choledocolithiasis is reported to be increasing in children. As for the adult population, several different therapeutic strategies have been described, however it is unclear which of those should be considered the gold standard. There is evidence‐based literature in adults that supports a combined “rendez‐vous” endoscopic retrograde cholangiopancreatography‐laparoscopic cholecystectomy technique. This allows management of the choledocholithiasis during the same anesthetic episode as the cholecystectomy. By contrast, there are just two case reports in children reporting this approach. The aim of this study is to report our experience with this technique in a series of children with choledocholithiasis.

Methods:

All patients who underwent the “rendez‐vous technique” at our institution between 2009 and 2020 were reviewed and evaluated for outcomes and complications.

Results:

Eleven children with cholecysto‐choledocholithiasis were evaluated: the procedure was successful in 10 whereas in one patient it was aborted due to technical difficulties. All patients resolved their clinical condition without major complications.

Conclusion:

To our knowledge, this is the first consistent series of “rendez‐vous technique” in the pediatric population, proving its feasibility and safety.
Tear Trough Filler Techniques Utilizing Hyaluronic Acid: A Systematic Review
Authors: Rao Babar K. , Berger Lauren E. , Reilly Catherine , Alamgir Mahin , Galadari Hassan
Published: March 2022

Background:

Hyaluronic acid soft-tissue augmentation fillers are commonly injected into multiple areas of the face, including the tear trough. Despite well-documented risks, there is no standardized, evidence-based approach to inject filler in this area, be it using a hypodermic needle or a microcannula. The authors, therefore, sought to establish a preference between the two methods to facilitate progression toward standardization and prevention of adverse events.

Methods:

This is a systematic review of articles discussing hyaluronic acid tear trough injection techniques performed in vivo and related outcomes. Searches were conducted across The Cochrane Library, PubMed, Scopus, Web of Science, and Embase to yield relevant articles published before February of 2020. All selected articles incorporated discrete patient cases and were analyzed by a variety of variables assessing evidence strength, outcomes, technique, and patient safety.

Results:

After appraisal, 42 articles met eligibility criteria: 20 using needles, 12 using cannulas, and 10 focusing on adverse events. Level III was the most commonly awarded evidence grade, corresponding to retrospective, nonexperimental descriptive studies. There were no statistically significant differences in reported aesthetic results, patient satisfaction, or incidence of adverse events across the needle-based and cannula-based articles. Some technique trends, such as targeted anatomical plane and needle position, emerged in subsequent articles.

Conclusion:

Given that there were no statistically significant differences in patient safety or outcomes, an evidence-based preference for needle or cannula injection into the tear trough cannot be made at this time. Current inconsistencies make tear trough injection procedures difficult to replicate, making standardization based on avoidance of adverse events not feasible.
Results of a Phase II Study on the Use of Neoadjuvant Chemotherapy (FOLFIRINOX or GEM/nab-PTX) for Borderline-resectable Pancreatic Cancer (NUPAT-01)
Authors: Yamaguchi Junpei , Yokoyama Yukihiro , Fujii Tsutomu , Yamada Suguru , Takami Hideki , Kawashima Hiroki , Ohno Eizaburo , Ishikawa Takuya , Maeda Osamu , Ogawa Hiroshi , Kodera Yasuhiro , Nagino Masato , Ebata Tomoki
Published: March 2022

Objective:

Given the frequent adverse events with multidrug chemotherapy, not only the survival benefit but also the feasibility of using neoadjuvant chemotherapy to treat pancreatic cancer need to be clarified.

Summary of Background Data:

Although the development of multidrug chemotherapy regimens has improved the survival outcomes of patients with unresectable pancreatic cancer, the benefits of these treatments in the neo-adjuvant setting remain controversial.

Methods:

Patients with borderline-resectable pancreatic cancer were enrolled and randomly assigned to receive neoadjuvant chemotherapy with either FOLFIRINOX or gemcitabine with nab-paclitaxel (GEM/nab-PTX). After the completion of chemotherapy, patients underwent surgical resection when feasible. This study (NUPAT-01) was a randomized phase II trial, and the primary endpoint was the R0 resection rate.

Results:

Fifty-one patients were enrolled in this study [FOLFIRINOX (n = 26) and GEM/nab-PTX (n = 25)]. A total of 84.3% (n = 43/51) of the patients eventually underwent surgery, and R0 resection was achieved in 67.4% (n = 33/ 51) of the patients. Adverse events (grade >3) due to neoadjuvant treatment were observed in 45.1% of the patients (n = 23/51), and major surgical complications occurred in 30.0% (n = 13/43), with no mortality noted. The intention-to-treat analysis showed that the 3-year overall survival rate was 54.7%, with a median survival time of 39.4 months, and a significant difference in overall survival was not observed between the FOLFIRINOX and GEM/nab-PTX groups.

Conclusions:

These results indicate that neoadjuvant chemotherapy with FOLFIRINOX or GEM/nab-PTX is feasible and well tolerated, achieving an R0 resection rate of 67.4%. The survival of patients was even found to be favorable in the intention-to-treat analysis.
Combined Partial Toupet Fundoplication With Laparoscopic Sleeve Gastrectomy for Patients With Morbid Obesity and Symptomatic GERD: Preliminary Results of the T-sleeve Technique
Authors: Türkçapar Ahmet G. , Şen Ozan
Published: March 2022

Aim:

The aim of this study to reveal preliminary results of our Toupet-sleeve technique in morbid obese patients with symptomatic gastroesophageal reflux disease (GERD) and compare their outcomes with laparoscopic sleeve gastrectomy (LSG) patients’ outcomes.

Methods:

The study included 103 patients who underwent primary LSG between March 2018 and October 2020 and 18 patients who underwent partial T-sleeve. Patients were stratified into 2 groups according to the surgical technique. All of the patients had preoperative symptomatic GERD. Patients were reevaluated with regard to GERD symptoms and weight loss in the postoperative period. Two groups’ data were compared.

Results:

The mean age of the patients was 39.2±10.2 years (63% female), and the mean body mass index was 43.2±6.4 kg/m2. The median operative time was 93 minutes (75 to 110 min) in group A (primary LSG) and 110 minutes (90 to 120 min) in group B (partial T-sleeve). The mean body mass index decreased to 28±4.5 kg/m2 in group A and 25.8±3.5 kg/m2 in group B at 12 months after the surgery. At the 12th month, the patients were reevaluated for GERD symptoms. Reflux symptoms were found to be resolved in 62% of the patients (n=64) in group A, while 32% of the patients (n=39) had persistent GERD symptoms. In group B, all of the patients had discontinued proton pump inhibitors postoperatively, and GERD symptoms were completely resolved in 94% of these patients (n=17).

Conclusions:

The present study showed that T-sleeve provides a very good weight loss and reflux control in patients with symptomatic GERD with morbid obesity in the short-term period. This technique can be proposed in some cases as a primary treatment modality. High numbers of patients and longer follow-up are needed.