bluuebunny/crossref_metadata_2025 huggingface dataset:
A Systematic Review of Dietary Supplements and Alternative Therapies for Weight Loss
Authors: Batsis John A. , Apolzan John W. , Bagley Pamela J. , Blunt Heather B. , Divan Vidita , Gill Sonia , Golden Angela , Gundumraj Shalini , Heymsfield Steven B. , Kahan Scott , Kopatsis Katherine , Port Ava , Parks Elizabeth Prout , Reilly Clifford A. , Rubino Domenica , Saunders Katherine H. , Shean Ryan , Tabaza Luai , Stanley Abishek , Tchang Beverly G. , Gundumraj Shivani , Kidambi Srividya
Published: June 2021

Objective

Dietary supplements and alternative therapies are commercialized as a panacea for obesity/weight gain as a result of the minimal regulatory requirements in demonstrating efficacy. These products may indirectly undermine the value of guideline‐driven obesity treatments. Included in this study is a systematic review of the literature of purported dietary supplements and alternative therapies for weight loss.

Methods

A systematic review was conducted to evaluate the efficacy of dietary supplements and alternative therapies for weight loss in participants aged ≥18 years. Searches of Medline (PubMed), Cochrane Library, Web of Science, CINAHL, and Embase (Ovid) were conducted. Risk of bias and results were summarized qualitatively.

Results

Of the 20,504 citations retrieved in the database search, 1,743 full‐text articles were reviewed, 315 of which were randomized controlled trials evaluating the efficacy of 14 purported dietary supplements, therapies, or a combination thereof. Risk of bias and sufficiency of data varied widely. Few studies (n = 52 [16.5%]) were classified as low risk and sufficient to support efficacy. Of these, only 16 (31%) noted significant pre/post intergroup differences in weight (range: 0.3‐4.93 kg).

Conclusions

Dietary supplements and alternative therapies for weight loss have a limited high‐quality evidence base of efficacy. Practitioners and patients should be aware of the scientific evidence of claims before recommending use.
Dietary supplements and alternative therapies for obesity: A Perspective from The Obesity Society’s Clinical Committee
Authors: Kidambi Srividya , Batsis John A. , Donahoo William T. , Jastreboff Ania M. , Kahan Scott , Saunders Katherine H. , Heymsfield Steven B.
Published: June 2021

In this Perspective Statement from The Obesity Society, the Clinical Committee discusses the use of weight loss supplements in the United States and the lack of regulatory oversight and rigorous testing of their efficacy and safety. A number of products and services claiming to promote weight loss are directly marketed to individuals with obesity and those wanting to lose weight. These products are not regulated as “drugs” by the Federal Drug Administration but, rather, are treated as dietary supplements if ingredients are “generally regarded as safe,” requiring little or no testing to show efficacy or safety. Health care providers should be aware of the lack of evidence and deficiencies in regulatory oversight of dietary supplements marketed for weight loss. Regulatory authorities should protect consumers by ensuring accurate and safe marketing claims and preventing promotion of unproven and potentially unsafe products and claims.
Knowledge and attitudes regarding non‐invasive prenatal testing among women in Saudi Arabia
Authors: Bawazeer Shahad , AlSayed Moeenaldeen , Kurdi Wesam , Balobaid Ameera
Published: June 2021

Objectives

To explore women's knowledge and attitudes regarding NIPT, its implications, the factors affecting their decision to undergo the test and actions taken following a positive result.

Methods

In this descriptive study, women who were offered NIPT through the foetal maternal clinic, were asked to complete an anonymous questionnaire about NIPT. The questionnaire consisted of 29 statements and covered four areas: demographics, knowledge, attitudes and decision‐making.

Results

A total of 150 women who were offered NIPT participated in this study. The results showed that generally women had poor knowledge of critical aspects of NIPT. This included the conditions tested for, the implications of the test and its limitations. Over 90% of women were in favour of NIPT and it being offered to all women of advanced maternal age while 66% of the tested women agreed to having confirmatory invasive testing in the case of a positive result.

Conclusion

This study shows that the acceptance rate for NIPT is high despite incomplete understanding of the benefits and limitations of the test. The study findings support the need for education regarding this test through dedicated genetic counselling sessions in order to ensure that an informed decision can be made.
Screening for distress and needs: Findings from a multinational validation of the Adolescent and Young Adult Psycho‐Oncology Screening Tool with newly diagnosed patients
Authors: Patterson Pandora , D'Agostino Norma M. , McDonald Fiona E. J. , Church Terry David , Costa Daniel S. J. , Rae Charlene S. , Siegel Stuart E. , Hu James , Bibby Helen , Stark Dan P. ,   International AYA Cancer Distress Screening Group
Published: June 2021

Objective

Adolescents and young adults (AYAs) diagnosed with cancer commonly experience elevated psychological distress and need appropriate detection and management of the psychosocial impact of their illness and treatment. This paper describes the multinational validation of the Distress Thermometer (DT) for AYAs recently diagnosed with cancer and the relationship between distress and patient concerns on the AYA‐Needs Assessment (AYA‐NA).

Methods

AYA patients (N = 288; 15–29 years, Mage = 21.5 years, SDage = 3.8) from Australia (n = 111), Canada (n = 67), the UK (n = 85) and the USA (n = 25) completed the DT, AYA‐NA, Hospital Anxiety Depression Scale (HADS) and demographic measures within 3 months of diagnosis. Using the HADS as a criterion, receiver operating characteristics analysis was used to determine the optimal cut‐off score and meet the acceptable level of 0.70 for sensitivity and specificity. Correlations between the DT and HADS scores, prevalence of distress and AYA‐NA scores were reported.

Results

The DT correlated strongly with the HADS‐Total, providing construct validity evidence (r = 0.65, p < 0.001). A score of 5 resulted in the best clinical screening cut‐off on the DT (sensitivity = 82%, specificity = 75%, Youden Index = 0.57). Forty‐two percent of AYAs scored at or above 5. ‘Loss of meaning or purpose’ was the AYA‐NA item most likely to differentiate distressed AYAs.

Conclusions

The DT is a valid distress screening instrument for AYAs with cancer. The AYA‐POST (DT and AYA‐NA) provides clinicians with a critical tool to assess the psychosocial well‐being of this group, allowing for the provision of personalised support and care responsive to individuals' specific needs and concerns.
Triptolide promotes the apoptosis and attenuates the inflammation of fibroblast‐like synoviocytes in rheumatoid arthritis by down‐regulating lncRNA ENST00000619282
Authors: Wen Jianting , Liu Jian , Wang Xin , Wang Jie
Published: June 2021

Rheumatoid arthritis (RA), recognized as a common chronic autoimmune disease, is characterized by the excessive proliferation and inflammatory infiltration of fibroblast‐like synoviocytes (FLS). In this study, our purpose is to elucidate the mechanisms of triptolide (TPL) in the treatment of RA by regulating the long non‐coding RNA (lncRNA) ENST00000619282, which promoted apoptosis and reduced inflammatory infiltration of FLS in RA (RA‐FLS). RA‐FLS was treated with different concentrations of TPL at different time points. CCK‐8 assay, ELISA, RT‐qPCR, immunofluorescence, TUNEL assay, and the transmission electron microscopy were used to measure the changes of cell viability, apoptosis, and the release of inflammatory cytokines. Next, the involvement of ENST00000619282 in TPL‐mediated protection against RA was explored. ENST00000619282 expression was significantly increased in the peripheral blood mononuclear cells (PBMCs) of RA patients. ENST0000061928 expression in RA PBMCs was positively associated with ESR, RF, CCP, and DAS28, while TPL treatment led to a downregulation of ENST00000619282. In addition, ENST00000619282 was significantly increased in RA‐FLS. Furthermore, overexpression of ENST00000619282 elevated the levels of pro‐apoptotic and pro‐inflammatory factors, while reduced the levels of anti‐apoptotic proteins and antiinflammatory factors. Besides, TPL treatment could reverse these effects by ENST00000619282 overexpression. The anti‐RA potential of TPL might be achieved by downregulating ENST00000619282, thereby promoting apoptosis, and reducing the inflammatory response in RA.
Electronic and thermo‐physical properties of double antiperovskites X6SOA2 (X = Na, K and A = Cl, Br, I): A non‐toxic and efficient energy storage materials
Authors: Rani Upasana , Kamlesh Peeyush Kumar , Agarwal Rohit , Kumari Jyoti , Verma Ajay Singh
Published: June 2021

We have explored the structural, electronic and transport parameters of cubic double antiperovskite structure X6SOA2 (X = Na, K and A = Cl, Br, I) using density functional theory followed by the solution of Boltzmann transport equation with constant relaxation time approximation. The exchange and correlation potential are described by the PBE‐GGA; the Becke‐Johnson approach modified by Tran and Blaha (TB‐mBJ) has been used to model the exchange‐correlation potential. Band gap of these materials have been found in between 2.85–4.24 eV. Thermoelectric properties have been computed at 300, 600 and 900 K. It has been found that figure of merit of double antiperovskite materials approaches to unity in both n‐ and p‐type regions. Hence these materials may turn out to be potential thermoelectric candidates. As these properties of the titled compounds have been explored for the very first time, hence, this work may open a new panorama for various detailed experimental and theoretical studies in the quest for non‐toxic, environmentally safe, and efficient energy sources.
Daporinad in vitro metabolite profiling via rat, dog, monkey and human liver microsomes by liquid chromatography/quadrupole‐orbitrap mass spectrometry
Authors: Qu Shan‐Dan , Liu Guang‐Xuan
Published: June 2021

Rationale

Daporinad is a novel and potent inhibitor of nicotinamide phosphoribosyl transferase with potential antineoplastic and antiangiogenic activities. We aimed to explore the metabolites of daporinad generated from liver microsomes and to propose metabolic pathways.

Methods

The metabolites were generated by individually incubating daporinad (10 μM) with liver microsomes at 37°C for 60 min. The metabolites were identified by ultra‐high‐performance liquid chromatography/quadrupole‐orbitrap mass spectrometry (UPLC/Q‐Orbitrap‐MS) using electrospray ionization in positive ion mode. They were deduced by accurate MS and MS/MS data.

Results

In total, 16 metabolites were found and their identities were characterized. In rat, dog and human, they were minor; in monkey, M11 was the most abundant. Daporinad was metabolized mainly through N‐dealkylation, amide hydrolysis, hydrogenation, oxygenation and dehydrogenation. There was no human‐specific metabolite.

Conclusions

The current study provided an overview of the metabolism of daporinad, which is helpful in predicting in vivo metabolites and in selecting animal species for toxicology studies.
Event‐triggered finite‐time H∞ output tracking control of switched systems with round‐robin protocol and its applications
Authors: Ren Hangli , Zong Guangdeng , Shi Kaibo
Published: June 2021

In this article, the finite‐time H∞ output tracking control problem is addressed for the networked switched systems. A hybrid event‐triggered scheme is introduced to reduce the network transmission overload. A round‐robin communication protocol is structured to determine the access rights of the sensor and alleviate the bandwidth pressure as well. Sufficient criteria for finite‐time stability of the closed‐loop systems with asynchronous switching characteristics are derived by resorting to a double‐mode dependent Lyapunov–Krasovskii functional. Finally, an application example of the buck‐boost converter circuit model is demonstrated to illustrate the effectiveness of the developed methods.
Glucose Oxidase Induces Mobilization of Long-Term Repopulating Hematopoietic Cells in Mice
Authors: So Han-Sol , Kim Min-Guk , Lee Jeong-Chae , Kook Sung-Ho
Published: June 2021

Hematopoietic stem progenitor cells (HSPCs) mobilized to peripheral blood, rather than those remaining in the bone marrow (BM), are commonly used as stem cell source in the clinic. As reactive oxygen species (ROS) are suggested as mediator of HSPC mobilization, we examined the impacts of glucose oxidase (GO) on peripheral mobilization of BM HSPCs and the associated mechanisms. Intravenous injection of GO induced HSPC mobilization even by single treatment, and the GO-mobilized cells maintained their long-term reconstituting and differentiating potentials in conditioned recipients. GO-injected mice lived a normal life without adverse effects such as stem cell senescence, hematopoietic disorders, and blood parameter alteration. The mobilization effect of GO was even evident in animal models showing poor mobilization, such as old, 5-fluorouracil-treated, or alendronate-treated mice. Importantly, combined injection of GO with granulocyte colony-stimulating factor (G-CSF) and/or AMD3100 enhanced more greatly HSPC mobilization than did G-CSF, AMD3100, or both. The GO-stimulated HSPC mobilization was almost completely attenuated by N -acetyl-L-cysteine treatment. Collectively, our results not only highlight the potential role of GO in HSPC mobilization via ROS signaling, but also provide a GO-based new strategy to improve HSPC mobilization in poorly mobilizing allogeneic or autologous donors via combination with G-CSF and/or AMD3100.
Transformative social policies as an essential buffer during socio‐economic crises
Authors: Kempf Isabell , Dutta Paramita
Published: June 2021

The current COVID‐19 crisis raises the question of the role of transformative social policies (TSPs) during socio‐economic crises. We used recent findings from an UNRISD survey of vulnerabilities and ILO's Social Protection Spotlight to examine the different roles of TSPs in the response to the COVID‐19 crisis. We found that all TSPs are important, especially in terms of reaching vulnerable groups. They need, however, to be used simultaneously in an integrated manner to be successful and should be linked to crisis and disaster management. It is also important to enhance targeting of vulnerable groups within universalism to protect groups of individuals who require additional or different kinds of support, for example, migrant or informal workers. If these additional integrated policies become part of long‐term development policies, they could be instrumental in ensuring that no one is left behind when the SDGs are implemented.
On the time‐varying predictive performance of longitudinal biomarkers: Measure and estimation
Authors: Zhang Jing , Ning Jing , Huang Xuelin , Li Ruosha
Published: June 2021

In many biomedical studies, participants are monitored at periodic visits until the occurrence of the failure event. Biomarkers are often measured repeatedly during these visits, and such measurements can facilitate updated disease prediction. In this work, we propose a two‐dimensional incident dynamic area under curve (AUC), to capture the variability due to both the biomarker assessment time and the prediction time to comprehensively quantify the predictive performance of a longitudinal biomarker. We propose a pseudo partial‐likelihood to achieve consistent estimation of the AUC under two realistic scenarios of visit schedules. Variance estimation methods are designed to facilitate inferential procedures. We examine the finite‐sample performance of our method through extensive simulations. The methods are applied to a study of chronic myeloid leukemia to evaluate the predictive performance of longitudinally collected gene expression levels.
How ecosystem structure affects firm performance in response to a negative shock to interdependencies
Authors: Burford Natalie , Shipilov Andrew V. , Furr Nathan R.
Published: June 2021

We evaluate the effects of component choices on firms' performance following a negative shock to the ecosystem's alignment structure. We advance a theoretical framework that relates three levels of ecosystem structure—local component interdependence, component clusters, and central components—to the firms' performance. In the setting of the e‐commerce industry impacted by the General Data Protection Regulation, our results support the predictions that a reduction in local component interdependence and an increase in component dispersion across clusters have a positive effect on firm performance, but the impact of an increased use of central components disappears when controlling for local interdependence. These findings contribute to the literature on performance consequences of structures of interdependencies within innovation ecosystems.

Managerial summary

We use data on the component choices of e‐commerce firms to study how the structure of the business ecosystem around these components affects firms' performance following a negative shock. We find that while firms which increased interdependence among their components may fare well in a stable environment, their performance will suffer following a negative shock relative to those that are not affected by the shock. Second, firms that draw their components from multiple component clusters perform better during a negative shock relative to those unaffected by the shock. Executives should actively manage the interdependencies among their technological components at different levels. This will help their firms to remain flexible, minimize disruption, allow for innovative recombination and prepare for future technological developments.
Unclonable Micro‐Texture with Clonable Micro‐Shape towards Rapid, Convenient, and Low‐Cost Fluorescent Anti‐Counterfeiting Labels
Authors: Lin Yuhong , Zhang Hongkun , Feng Jingyun , Shi Bori , Zhang Mengying , Han Yuexing , Wen Weijia , Zhang Tongyi , Qi Yabing , Wu Jinbo
Published: June 2021

An ideal anti‐counterfeiting label not only needs to be unclonable and accurate but also must consider cost and efficiency. But the traditional physical unclonable function (PUF) recognition technology must match all the images in a database one by one. The matching time increases with the number of samples. Here, a new kind of PUF anti‐counterfeiting label is introduced with high modifiability, low reagent cost (2.1 × 10−4 USD), simple and fast authentication (overall time 12.17 s), high encoding capacity (2.1 × 10623), and its identification software. All inorganic perovskite nanocrystalline films with clonable micro‐profile and unclonable micro‐texture are prepared by laser engraving for lyophilic patterning, liquid strip sliding for high throughput droplet generation, and evaporative self‐assembling for thin film deposition. A variety of crystal film profile shapes can be used as “specificator” for image recognition, and the verification time of recognition technology based on this divide‐and‐conquer strategy can be decreased by more than 20 times.
Hierarchical Co0.85Se‐CdSe/MoSe2/CdSe Sandwich‐Like Heterostructured Cages for Efficient Photocatalytic CO2 Reduction
Authors: Du Lizhi , Chen Yajie , Wang Qi , Zhao Yumeng , Li Longge , Liu Xiu , Tian Guohui
Published: June 2021

Fabricating efficient photocatalysts with rapid charge carrier separation and high visible light harvesting is an advisable strategy to improve CO2 reduction performance. Herein, hierarchical Co0.85Se‐CdSe/MoSe2/CdSe cages with sandwich‐like heterostructure are prepared to act as efficient photocatalysts for CO2 reduction. In this study, the structure and composition of the final products can be regulated through the cation‐exchange reaction in the presence of ascorbic acid. In the Co0.85Se‐CdSe/MoSe2/CdSe cages, MoSe2 nanosheets function as a bridge to integrate Co0.85Se‐CdSe and CdSe on both sides of the MoSe2 nanosheet shell into a sandwich‐like heterostructured catalyst system, which possesses multiple positive merits for photocatalysis, including accelerated transport and separation of photogenerated carriers, improved visible light utilization, and increased catalytic active sites. Thus, the optimized Co0.85Se‐CdSe/MoSe2/CdSe cages exhibit remarkable visible‐light photocatalytic performance and outstanding stability for CO2 reduction with a high CO average yield of 15.04 µmol g−1 h−1 and 90.14% selectivity, which are much higher than those of other control samples including single‐component catalysts and binary hybrid catalysts. This study provides a promising way for the design and fabrication of high‐efficiency photocatalysts.
Cobalt‐Enhanced Mass Transfer and Catalytic Production of Sulfate Radicals in MOF‐Derived CeO2 • Co3O4 Nanoflowers for Efficient Degradation of Antibiotics
Authors: Zhao Shiyin , Long Yangke , Su Yiping , Wang Shubin , Zhang Zuotai , Zhang Xuanjun
Published: June 2021

Antibiotics discharge has been a critical issue as the abuse in clinical disease treatment and aquaculture industry. Advanced oxidation process (AOPs) is regarded as a promising approach to degrade organic pollutants from wastewater, however, the catalysts for AOPs always present low activities, and uncontrollable porosities, thus hindering their further wider applications. In this work, an aliovalent‐substitution strategy is employed in metal‐organic framework (MOF) precursors assembly, aiming to introduce Co(II/III) into Ce‐O clusters which could modify the structure of the clusters, then change the crystallization, enlarge the surface area, and regulate the morphology. The introduction of Co(II/III) also enlarges the pore size for mass transfer and enriches the active sites for the production of sulfate radicals (SO4• −) in MOF‐derived catalysts, leading to excellent performance in antibiotics removal. Significantly, the CeO2•Co3O4 nanoflowers could efficiently enhance the generation of sulfate radical SO4• − and promote the norfloxacin removal efficiency to 99% within 20 min. The CeO2•Co3O4 nanoflowers also present remarkable universality toward various antibiotics and organic pollutants. The aliovalent‐substitution strategy is anticipated to find wide use in the exploration of high‐performance MOF‐derived catalysts for various applications.
Coordinated Adsorption and Catalytic Conversion of Polysulfides Enabled by Perovskite Bimetallic Hydroxide Nanocages for Lithium‐Sulfur Batteries
Authors: Wang Xinliang , Han Junwei , Luo Chong , Zhang Bin , Ma Jiabin , Li Zejian , He Yan‐Bing , Yang Quan‐Hong , Kang Feiyu , Lv Wei
Published: June 2021

Catalysis is an effective remedy for the fast capacity decay of lithium‐sulfur batteries induced by the shuttling of lithium polysulfides (LiPSs), but too strong adsorption ability of many catalysts toward LiPSs increases the risk of catalyst passivation and restricts the diffusion of LiPSs for conversion. Herein, perovskite bimetallic hydroxide (CoSn(OH)6) nanocages are prepared, which are further wrapped by reduced graphene oxide (rGO) as the catalytic host for sulfur. Because of the coordinated valence state of Co and Sn and the intrinsic defect of the perovskite structure, such bimetallic hydroxide delivers moderate adsorption ability and enhanced catalytic activity toward LiPS conversion. Coupled with the hollow structure and the wrapped rGO as double physical barriers, the redox reaction kinetics, and sulfur utilization are effectively improved with such a host. The assembled battery delivers a good rate performance with a high capacity of 644 mAh g−1 at 2 C and long stability with a capacity decay of 0.068% per cycle over 600 cycles at 1 C. Even with a higher sulfur loading of 3.2 mg cm−2 and a low electrolyte/sulfur ratio of 5 µL mg−1, the battery still shows high sulfur utilization and good cycling stability.
Electrochemical Methane Conversion
Authors: Wang Qihao , Kan Miao , Han Qing , Zheng Gengfeng
Published: June 2021

Methane, as an earth‐abundant C1 resource, is a greenhouse gas as well as a key building block in the chemical industry. Electrochemical conversion of methane into fuels and valuable chemicals represents an attractive promise toward carbon neutralization and reducing CO2 emission in industrial methane reforming. To overcome the catalyst degradation and energy cost problems, it is critical to activate the CH bonds in methane effectively to operate under ambient conditions, while without the cost of product selectivity. This review focuses on catalyst structures and system design strategies in recent developments of electrocatalytic methane conversion progresses. The combination of electro‐, thermo‐, and photocatalytic methods can enable complementary and enhanced activities, as well as new insights in reaction conditions and mechanisms.
Engineering Cocatalysts onto Low‐Dimensional Photocatalysts for CO2 Reduction
Authors: Di Jun , Lin Bo , Tang Bijun , Guo Shasha , Zhou Jiadong , Liu Zheng
Published: June 2021

Low‐dimensional semiconductors are regarded as alternative architectures to achieve high‐efficiency photocatalytic CO2 reduction activity due to the unique structural and electronic properties. However, the catalytic efficiency is still limited by two factors, namely, poor surface charge separation efficiency and lack of surface‐active sites for CO2 reduction. Herein, the state‐of‐the‐art progress of cocatalysts engineering is reviewed to ameliorate these issues, to acquire outstanding behavior. The fundamentals of cocatalysts for CO2 photoreduction along with some noteworthy points are presented. The strategies of engineering cocatalysts for performance optimization are summarized with the emphasis on structure–performance correlations, such as component engineering, phase engineering, facet engineering, size engineering, single‐atom engineering, crystallinity engineering, defect engineering, strain engineering, and interface engineering. Finally, this review is ended with an outlook on unsolved issues and perspectives over cocatalysts modified low‐dimensional photocatalysts.
Clinical presentation, genetic etiology and outcome associated with fetal cardiomyopathy: comparison of two eras
Authors: Trakmulkichkarn T. , Ghadiry‐Tavi R. , Fruitman D. , Niederhoffer K. Y. , Caluseriu O. , Lauzon J. L. , Wewala G. , Hornberger L. K. , Urschel S. , Conway J. , McBrien A.
Published: June 2021

Objective

To assess the rate and type of genetic diagnosis and clinical outcome of cases of fetal cardiomyopathy (CM) during two eras, in order to examine the impact of advanced genetic testing and improved perinatal management strategies.

Methods

All diagnoses of fetal CM in Alberta, Canada, encountered between 2003 and 2019, were reviewed retrospectively. Genetic, cardiac and non‐cardiac diagnoses and clinical outcome were documented. Cases with CM secondary to extracardiac pathology and maternal conditions were excluded. Cases diagnosed in the earlier era of the study period (2003–2012) were compared with those diagnosed in the later era (2013–2019).

Results

Thirty‐eight cases of fetal CM met the inclusion criteria. Median gestational age (GA) at diagnosis was 22.8 (range, 13.4–37.4) weeks. Associated structural heart disease was present in 39% (15/38) of cases and 24% (9/38) had arrhythmia. Hydrops was identified in 29% (11/38) of cases at presentation, and a further 18% (7/38) developed hydrops later in gestation. Twenty‐six percent (10/38) of cases underwent termination of pregnancy and 24% (9/38) had intrauterine death. Of liveborn cases, neonatal death occurred in 16% (3/19), late death occurred in 21% (4/19) and 63% (12/19) were alive at the last follow‐up. Excluding cases that had termination of pregnancy and those with a liveborn infant who received planned palliative care, the rate of neonatal survival was higher in the later compared with the earlier era (69% (11/16) vs 45% (5/11)), although the difference was not statistically significant (P = 0.26). A genetic etiology was confirmed in 39% (15/38) of cases and strongly suspected in 24% (9/38). A significantly higher proportion of cases had a confirmed or strongly suspected genetic etiology in the later era compared with in the earlier era (76% (19/25) vs 38% (5/13); P = 0.04).

Conclusions

In the recent era, a higher proportion of fetal CM cases had a confirmed or strongly suspected genetic etiology than reported previously. Based on comparison with older series, modern perinatal management strategies may not have a significant impact on neonatal survival in cases of fetal CM; however, a larger study would be better powered to detect more subtle differences. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
Low energy effective field theory operator basis at d ≤ 9
Authors: Li Hao-Lin , Ren Zhe , Xiao Ming-Lei , Yu Jiang-Hao , Zheng Yu-Hui
Published: June 2021

Abstract

We obtain the complete operator bases at mass dimensions 5, 6, 7, 8, 9 for the low energy effective field theory (LEFT), which parametrize various physics effects between the QCD scale and the electroweak scale. The independence of the operator basis regarding the equation of motion, integration by parts and flavor relations, is guaranteed by our algorithm [1, 2], whose validity for the LEFT with massive fermions involved is proved by a generalization of the amplitude-operator correspondence. At dimension 8 and 9, we list the 35058 (756) and 704584 (3686) operators for three (one) generations of fermions categorized by their baryon and lepton number violations (∆B, ∆L), as these operators are of most phenomenological relevance.
On Stability of a General Bilinear Functional Equation
Authors: Bahyrycz Anna , Sikorska Justyna
Published: June 2021

We prove the Hyers–Ulam stability of the functional equation $$\begin{aligned}&f(a_1x_1+a_2x_2,b_1y_1+b_2y_2)=C_{1}f(x_1,y_1)\nonumber \\ \nonumber \\&\quad +C_{2}f(x_1,y_2)+C_{3}f(x_2,y_1)+C_{4}f(x_2,y_2) \end{aligned}$$

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in the class of functions from a real or complex linear space into a Banach space over the same field. We also study, using the fixed point method, the generalized stability of $$(*)$$

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in the same class of functions. Our results generalize some known outcomes.
Contemporary trends for urological training and management of stress urinary incontinence in Ireland
Authors: MacCraith Eoin , Forde James C. , O’Brien Fergal J. , Davis Niall F.
Published: June 2021

Introduction and hypothesis

The aim of this study is to evaluate the trends in stress urinary incontinence (SUI) surgery since the 2018 pause on use of the polypropylene (PP) mid-urethral sling (MUS) and to quantify the effect this has had on surgical training.

Methods

Two anonymous surveys were sent to all current urology trainees and to all consultant surgeons who specialise in stress urinary incontinence surgery.

Results

Prior to the pause, 86% (6 out of 7) of consultant urologists and 73% (11 out of 15) of consultant gynaecologists would “always”/“often” perform MUS for SUI. After that, 100% (22 out of 22) of consultants reported that they “never” perform MUS. There has been a modest increase in the use of urethral bulking agent (UBA) procedures among urologists, with 43% (3 out of 7) now “often” performing this, compared with 71% (5 out of 7) “never” performing it pre-2018. Trainee exposure to SUI surgery reduced by 75% between 2016 and 2020. Despite a ten-fold increase in UBA procedures logged by trainees, the decline in MUS has resulted in a major reduction in total SUI surgeries. Coinciding with this decrease in surgeries, there was a 56% reduction in trainees’ self-assessed competence at SUI surgery. Thirteen percent of trainees are interested in specialising in Female Urology and those trainees had significantly greater exposure to SUI procedures during their training than those who did not (p = 0.0072).

Conclusions

This study has identified a downward trend in SUI surgery, which is concerning for the undertreatment of females with SUI. A decline in SUI surgery training has resulted in reduced trainee confidence and interest in this subspecialty.
Catalytic activity and stereoselectivity of engineered phosphotriesterases towards structurally different nerve agents in vitro
Authors: Köhler Anja , Escher Benjamin , Job Laura , Koller Marianne , Thiermann Horst , Skerra Arne , Worek Franz
Published: June 2021

Highly toxic organophosphorus nerve agents, especially the extremely stable and persistent V-type agents such as VX, still pose a threat to the human population and require effective medical countermeasures. Engineered mutants of the Brevundimonas diminuta phosphotriesterase (BdPTE) exhibit enhanced catalytic activities and have demonstrated detoxification in animal models, however, substrate specificity and fast plasma clearance limit their medical applicability. To allow better assessment of their substrate profiles, we have thoroughly investigated the catalytic efficacies of five BdPTE mutants with 17 different nerve agents using an AChE inhibition assay. In addition, we studied one BdPTE version that was fused with structurally disordered PAS polypeptides to enable delayed plasma clearance and one bispecific BdPTE with broadened substrate spectrum composed of two functionally distinct subunits connected by a PAS linker. Measured kcat/KM values were as high as 6.5 and 1.5 × 108 M−1 min−1 with G- and V-agents, respectively. Furthermore, the stereoselective degradation of VX enantiomers by the PASylated BdPTE-4 and the bispecific BdPTE-7 were investigated by chiral LC–MS/MS, resulting in a several fold faster hydrolysis of the more toxic P(−) VX stereoisomer compared to P(+) VX. In conclusion, the newly developed enzymes BdPTE-4 and BdPTE-7 have shown high catalytic efficacy towards structurally different nerve agents and stereoselectivity towards the toxic P(−) VX enantiomer in vitro and offer promise for use as bioscavengers in vivo.
Virasoro Constraints Revisited
Authors: Cassia Luca , Lodin Rebecca , Zabzine Maxim
Published: June 2021

We revisit the Virasoro constraints and explore the relation to the Hirota bilinear equations. We furthermore investigate and provide the solution to non-homogeneous Virasoro constraints, namely those coming from matrix models whose domain of integration has boundaries. In particular, we provide the example of Hermitean matrices with positive eigenvalues in which case one can find a solution by induction on the rank of the matrix model.
Lack of association between CYB5A gene rs1790834 polymorphism and the response to leflunomide in women with rheumatoid arthritis
Authors: Łączna Małgorzata , Malinowski Damian , Paradowska-Gorycka Agnieszka , Safranow Krzysztof , Dziedziejko Violetta , Pawlik Andrzej
Published: June 2021

Aim

Leflunomide is a disease-modifying antirheumatic drug used in therapy for rheumatoid arthritis (RA). Previous studies indicated that oestrogens and androgens may affect the response to leflunomide in RA patients. The synthesis of androgens is regulated by cytochrome CYB5A. The aim of this study was to examine the association between the CYB5A gene rs1790834 polymorphism and the response to leflunomide in women with RA.

Methods

The study included 111 women diagnosed with RA. Leflunomide was administered in monotherapy at a dose of 20 mg/day. All patients underwent a monthly evaluation for 12 months after the initiation of treatment with leflunomide.

Results

After 12 months of therapy, the changes in individual disease activity parameters, such as: DAS28, ESR, CRP and VAS, were not statistically significantly different between rs1790834 genotypes in the Kruskal–Wallis test.

Conclusions

The results of our study suggest lack of statistically significant association between the CYB5A gene rs1790834 polymorphism and the response to leflunomide in women with RA.
Real-world safety and efficacy data of immunotherapy in patients with cancer and autoimmune disease: the experience of the Hellenic Cooperative Oncology Group
Authors: Fountzilas Elena , Lampaki Sofia , Koliou Georgia-Angeliki , Koumarianou Anna , Levva Sofia , Vagionas Anastasios , Christopoulou Athina , Laloysis Athanasios , Psyrri Amanda , Binas Ioannis , Mountzios Giannis , Kentepozidis Nikolaos , Kotsakis Athanassios , Saloustros Emmanouil , Boutis Anastasios , Nikolaidi Adamantia , Fountzilas George , Georgoulias Vassilis , Chrysanthidis Miltiadis , Kotteas Elias , Vo Henry , Tsiatas Marinos , Res Eleni , Linardou Helena , Daoussis Dimitrios , Bompolaki Iliada , Andreadou Anna , Papaxoinis George , Spyratos Dionisios , Gogas Helen , Syrigos Konstantinos N. , Bafaloukos Dimitrios
Published: June 2021

Background

Data on the safety and efficacy of immune checkpoint inhibitors (ICI) in patients with concurrent autoimmune diseases (AID) are limited.

Methods

We performed a retrospective multicenter review of medical records of patients with cancer and underlying AID who received ICI. The primary endpoint was progression-free survival (PFS).

Results

Among 123 patients with pre-existing AID who received ICI, the majority had been diagnosed with non-small cell lung cancer (NSCLC, 68.3%) and melanoma (14.6%). Most patients had a rheumatologic (43.9%), or an endocrine disorder (21.1%). Overall, 74 (60.2%) patients experienced an immune-related adverse event (irAE) after ICI initiation, AID flare (25.2%), or new irAE (35%). Frequent irAEs included thyroiditis, dermatitis and colitis. ICI was permanently discontinued due to unacceptable (8.1%) or fatal (0.8%) toxicity. In patients with NSCLC, corticosteroid treatment at the initiation of immunotherapy was associated with poor PFS (HR = 2.78, 95% CI 1.40–5.50, p = 0.003). The occurrence of irAE was associated with increased PFS (HR = 0.48, 95% CI 0.25–0.92, p = 0.026). Both parameters maintained their independent prognostic significance.

Conclusions

ICI in patients with cancer and pre-existing AID is associated with manageable toxicity that infrequently requires treatment discontinuation. However, since severe AID flare might occur, expected ICI efficacy and toxicity must be balanced.

Clinical trial identifier

NCT04805099
Competition for S-containing amino acids between rhizosphere microorganisms and plant roots: the role of cysteine in plant S acquisition
Authors: Ma Qingxu , Hill Paul W. , Chadwick David R. , Wu Lianghuan , Jones Davey L.
Published: June 2021

Plant S deficiency is common, but the role of S-containing amino acids such as cysteine in plant S uptake is unknown. We applied 14C-, 35S-, 13C-, and 15N-labelled cysteine to wheat and oilseed rape rhizospheres and traced the plants’ elemental uptake. Both plants absorbed 0.37–0.81% of intact cysteine after 6 h with no further increase after 24 h. They absorbed 1.6–11.5% 35S and 12.3–7.6% 15N from cysteine after 24 h and utilised SO42− as their main S source (75.5–86.4%). Added and naturally occurring cysteine-S contributed 5.6 and 1.1% of total S uptake by wheat and oilseed rape, respectively. Cysteine and inorganic S derived from cysteine contributed 24.5 and 13.6% of uptake for wheat and oilseed rape, respectively, after 24 h. Oilseed rape absorbed ~10-fold more S from cysteine and SO42− than did wheat. The highest absorption of free cysteine should be in the organic-rich soil patches. Soil microorganisms rapidly decomposed cysteine (t1/2 = 1.37 h), and roots absorbed mineralised inorganic N and S. After 15 min, 11.7–14.3% of the 35S-cysteine was retained in the microbial biomass, while 30.2–36.7% of the SO42− was released, suggesting that rapid microbial S immobilisation occurs after cysteine addition. Plants acquire N and S from cysteine via unidirectional soil-to-root nutrient flow, and cysteine is an important S source for plants.
Sacral nerve stimulation in patients with ileal pouch-anal anastomosis
Authors: Seifarth C. , Slavova N. , Degro C. , Lehmann K. S. , Kreis M. E. , Weixler B.
Published: June 2021

Purpose

Functional results after proctocolectomy and ileal pouch-anal anastomosis (IPAA) are generally good. However, some patients suffer from high stool frequency or fecal incontinence. Sacral nerve stimulation (SNS) may represent a therapeutic alternative in these patients, but little is known about indication and results. The aim of this study was to evaluate incontinence after IPAA and demonstrate SNS feasibility in these patients.

Methods

This retrospective study includes patients who received a SNS between 1993 and 2020 for increased stool frequency or fecal incontinence after proctocolectomy with IPAA for ulcerative colitis. Proctocolectomy was performed in a two- or three-step approach with ileostomy closure as the last step. Demographic, follow-up data and functional results were obtained from the hospital database.

Results

SNS was performed in 23 patients. Median follow-up time after SNS was 6.5 years (min. 4.2–max. 8.8). Two patients were lost to follow-up. The median time from ileostomy closure to SNS implantation was 6 years (min. 0.5–max. 14.5). Continence after SNS improved in 16 patients (69%) with a median St. Marks score for anal incontinence of 19 (min. 4–max. 22) before SNS compared to 4 (0–10) after SNS placement (p = 0.012). In seven patients, SNS therapy was not successful.

Conclusion

SNS implantation improves symptoms in over two-thirds of patients suffering from high stool frequency or fecal incontinence after proctocolectomy with IPAA. Awareness of the beneficial effects of SNS should be increased in physicians involved in the management of these patients.
Appreciation and job control predict depressive symptoms: results from the Study on Mental Health at Work
Authors: Pohrt Anne , Fodor Daniel , Burr Hermann , Kendel Friederike
Published: June 2021

Objective

Depressive symptoms are a leading cause of disability retirement and sick leave. The aim of this study was to assess the risk of depressive symptoms in German employees and its associations with factors from both the occupational and the non-occupational domain and gender.

Methods

In the second wave of the German Study of Mental Health at Work (SMGA), a representative sample of 2640 German employees (52% women) was studied. Depressive symptoms were assessed with the PHQ-9 questionnaire. Psychosocial occupational and non-occupational conditions were assessed with quantitative interviews. In this cross-sectional sample, the association of these factors with depressive symptoms was examined using logistic regression models.

Results

Factors from both the occupational and the non-occupational domain were associated with risk of depressive symptoms. Low appreciation from superior (ORmen 2.1 (95% CI 1.2–3.7); ORwomen 3.2 (95% CI 2.1–4.8)), low job control (ORmen 2.9 (95% CI 1.6–5.4); ORwomen 1.6 (95% CI 1.0–2.5)), and critical life events (ORmen 3.0 (95% CI 1.6–5.4); ORwomen 2.3 (95% CI 1.5–3.7)) had the strongest association with risk of depressive symptoms. The association with quantitative demands was stronger in caregivers than in non-caregivers. The results indicated possible differences in the associations of working conditions between men and women, and between family caregivers and non-caregivers.

Conclusion

Factors from both work and private life are associated with depressive symptoms, especially appreciation, job control, and critical life events. Gender differences, with respect to appreciation and influence at work, suggest a more gender sensitive approach to psychosocial occupational health research and interventions.
A systematic review of the perforated duodenal diverticula: lessons learned from the last decade
Authors: Kapp Joshua R. , Müller Philip C. , Gertsch Philippe , Gubler Christoph , Clavien Pierre-Alain , Lehmann Kuno
Published: June 2021

Background

The perforated duodenal diverticulum remains a rare clinical entity, the optimal management of which has not been well established. Historically, primary surgery has been the preferred treatment modality. This was called into question during the last decade, with the successful application of non-operative therapy in selected patients. The aim of this systematic review is to identify cases of perforated duodenal diverticula published over the past decade and to assess any subsequent evolution in treatment.

Methods

A systematic review of English and non-English articles reporting on perforated duodenal diverticula using MEDLINE (2008–2020) was performed. Only cases of perforated duodenal diverticula in adults (> 18 years) that reported on diagnosis and treatment were included.

Results

Some 328 studies were identified, of which 31 articles met the inclusion criteria. These studies included a total of 47 patients with perforated duodenal diverticula. This series suggests a trend towards conservative management with 34% (16/47) of patients managed non-operatively. In 31% (5/16) patients initially managed conservatively, a step-up approach to surgical intervention was required.

Conclusion

Conservative treatment of perforated duodenal diverticula appears to be an acceptable and safe treatment strategy in stable patients without signs of peritonitis under careful observation. For patients who fail to respond to conservative treatment, a step-up approach to percutaneous drainage or surgery can be applied. If surgery is required, competence in techniques ranging from simple diverticulectomy to Roux-en-Y gastric diversion or even Whipple’s procedure may be required depending on tissue friability and diverticular collar size.
Introgression of the sesquiterpene biosynthesis from Solanum habrochaites to cultivated tomato offers insights into trichome morphology and arthropod resistance
Authors: Therezan Rodrigo , Kortbeek Ruy , Vendemiatti Eloisa , Legarrea Saioa , de Alencar Severino M. , Schuurink Robert C. , Bleeker Petra , Peres Lázaro E. P.
Published: June 2021

Main conclusion

Cultivated tomatoes harboring the plastid-derived sesquiterpenes from S. habrochaites have altered type-VI trichome morphology and unveil additional genetic components necessary for piercing-sucking pest resistance.

Arthropod resistance in the tomato wild relative Solanum habrochaites LA1777 is linked to specific sesquiterpene biosynthesis. The Sesquiterpene synthase 2 (SsT2) gene cluster on LA1777 chromosome 8 controls plastid-derived sesquiterpene synthesis. The main genes at SsT2 are Z-prenyltransferase (zFPS) and Santalene and Bergamotene Synthase (SBS), which produce α-santalene, β-bergamotene, and α-bergamotene in LA1777 round-shaped type-VI glandular trichomes. Cultivated tomatoes have mushroom-shaped type-VI trichomes with much smaller glands that contain low levels of monoterpenes and cytosolic-derived sesquiterpenes, not presenting the same pest resistance as in LA1777. We successfully transferred zFPS and SBS from LA1777 to cultivated tomato (cv. Micro-Tom, MT) by a backcrossing approach. The trichomes of the MT-Sst2 introgressed line produced high levels of the plastid-derived sesquiterpenes. The type-VI trichome internal storage-cavity size increased in MT-Sst2, probably as an effect of the increased amount of sesquiterpenes, although it was not enough to mimic the round-shaped LA1777 trichomes. The presence of high amounts of plastid-derived sesquiterpenes was also not sufficient to confer resistance to various tomato piercing-sucking pests, indicating that the effect of the sesquiterpenes found in the wild S. habrochaites can be insect specific. Our results provide for a better understanding of the morphology of S. habrochaites type-VI trichomes and paves the way to obtain insect-resistant tomatoes.