bluuebunny/crossref_metadata_2025 huggingface dataset:
A new knockdown resistance (kdr) mutation, F1534L, in the voltage-gated sodium channel of Aedes aegypti, co-occurring with F1534C, S989P and V1016G
Authors: Kushwah Raja Babu S. , Kaur Taranjeet , Dykes Cherry L. , Ravi Kumar H. , Kapoor Neera , Singh Om P.
Published: June 2020

Background

Aedes aegypti is a primary vector of dengue, chikungunya and Zika infections in India. In the absence of specific drugs or safe and effective vaccines for these infections, their control relies mainly on vector control measures. The emergence of insecticide resistance in vectors, especially against pyrethroids, is a serious threat to the insecticide-based vector control programme. This study reports the presence of multiple knockdown resistance (kdr) mutations present in an Ae. aegypti population from Bengaluru (India), including a new mutation F1534L.

Methods

Aedes aegypti collected from Bengaluru were subjected to insecticide susceptibility tests with DDT, deltamethrin and permethrin. The DNA sequencing of partial domain II, III and IV of the voltage-gated sodium channel (VGSC) was performed to screen kdr mutations present in the population and PCR-based assays were developed for their detection. Genotyping of kdr mutations was done using PCR-based assays, allelic frequencies were determined, and tests of genetic association of kdr mutations with the insecticide resistance phenotype were performed.

Results

The Ae. aegypti population was resistant to DDT, deltamethrin and permethrin. The DNA sequencing of the VGSC revealed the presence of four kdr mutations, i.e. S989P and V1016G in domain II and two alternative kdr mutations F1534C and F1534L in domain III. Allele-specific PCR assays (ASPCR) were developed for the detection of kdr mutations S989P and V1016G and an existing PCR-RFLP based strategy was modified for the genotyping of all three known kdr mutations in domain III (F1534L, F1534C and T1520I). Genotyping of Ae. aegypti samples revealed a moderate frequency of S989P/V1016G (18.27%) and F1534L (17.48%), a relatively high frequency of F1534C (50.61%) and absence of T1520I in the population. Mutations S989P and V1016G were in complete linkage disequilibrium in this population while they were in linkage equilibrium with kdr mutations F1534C and F1534L. The alleles F1534C and F1534L are genetically associated with permethrin resistance.

Conclusions

A new kdr mutation, F1534L, was found in an Ae. aegypti population from Bengaluru (India), co-occurring with the other three mutations S989P, V1016G and F1534C. The findings of a new mutation have implications for insecticide resistance management.
Repeated assessment of work-related exhaustion: the temporal stability of ratings in the Lund University Checklist for Incipient Exhaustion
Authors: Persson Roger , Österberg Kai
Published: June 2020

Objective

Screening inventories are important tools in clinical settings and research but may be sensitive to temporary fluctuations. Therefore, we revisited data from a longitudinal study with the Lund University Checklist for Incipient Exhaustion (LUCIE) that comprised occupationally active individuals (n = 1355; 27–52 years; 57% women) and one initial paper and pencil survey and 10 subsequent equally spaced online surveys. In the present study we examine to what extent the LUCIE scores changed across 3 years (11 assessments) and whether episodes of temporary elevated LUCIE scores (LTE) coincided with reports of negative or positive changes at work or in private life.

Results

In the total sample, the prevalence rates for the four LUCIE classifications of signs of increasing exhaustion (from no exhaustion to possible exhaustion disorder) ranged from 65.4–73.0%, 16.6–20.9%, 6.2–9.6%, and 3.4–5.0%. Of 732 individuals screened for LTE episodes, 16% had an LTE episode. The LTE episodes typically coincided with reports of adverse changes at work or, to a lesser extent, in private life. Thus, LUCIE classifications appear reliable and lend themselves to repeated use on the same individuals, or group of individuals. Even single episodes of elevated LUCIE scores seem appropriately to indicate adverse reactions to the work situation.
Prevalence and susceptibility to antibiotics from Campylobacter jejuni and Campylobacter coli isolated from chicken meat in southern Benin, West Africa
Authors: Kouglenou Sylvain Daton , Agbankpe Alidehou Jerrold , Dougnon Victorien , Djeuda Armando Djiyou , Deguenon Esther , Hidjo Marie , Baba-Moussa Lamine , Bankole Honore
Published: June 2020

Objective

Poultry is commonly considered to be the primary vehicle for Campylobacter infection in humans. The aim of this study is to assess the risk of Campylobacteriosis in chicken meat consumers in southern Benin by assessing the prevalence and resistance profile of Campylobacter coli and Campylobacter jejuni isolated from chicken thigh in Southern Benin.

Results

The contamination rate of Campylobacter in the samples was 32.8%. From this percentage, 59.5% were local chicken thighs and 40.5% of imported chicken thighs (p = 0.045). After molecular identification, on the 256 samples analyzed, the prevalence of C. jejuni was 23.4% and 7.8% for C. coli, with a concordance of 0.693 (Kappa coefficient of concordance) with the results from phenotypic identification. Seventy-two-point seven percent of Campylobacter strains were resistant to Ciprofloxacin, 71.4% were resistant to Ampicillin and Tetracycline. 55.8% of the strains were multi-drug resistant.
Correction to: DNA methylation changes during preimplantation development reveal interspecies differences and reprogramming events at imprinted genes
Authors: Ivanova Elena , Canovas Sebastian , Garcia-Martínez Soledad , Romar Raquel , Lopes Jordana S. , Rizos Dimitrios , Sanchez-Calabuig Maria J. , Krueger Felix , Andrews Simon , Perez-Sanz Fernando , Kelsey Gavin , Coy Pilar
Published: June 2020

An amendment to this paper has been published and can be accessed via the original article.
Incidence of malignancy in patients with common variable immunodeficiency according to therapeutic delay: an Italian retrospective, monocentric cohort study
Authors: Pedini Veronica , Verga Jacopo Umberto , Terrenato Irene , Menghini Denise , Mezzanotte Cristina , Danieli Maria Giovanna
Published: June 2020

Background

Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency and has a broad spectrum of clinical manifestations. Among non-infectious complications, an increased incidence of malignancies may have a special relevance for survival, but little is known about treatment efficacy on malignant complications.

Methods

This was a monocenter retrospective study on CVID patients, designed to provide preliminary data for the investigation of the possible link between therapeutic delay and tumor incidence.

Results

A total of 67 CVID subjects were included. The median diagnostic delay was 7.5 years (range: 0–63 years), and the median therapeutic delay was 8.5 years (range: 0–67 years). Malignancies were diagnosed in 18 (27%) patients. Eight out of 18 (44%) patients with a malignancy had lymphoma. Patients who developed a malignancy showed a longer therapeutic delay in comparison to patients with no malignancy, although no statistical significance was achieved (11 years vs 8 years, respectively, p = 0.424). We observed a lower frequency of malignancy in CVID patients with reduced therapeutic delay compared with patients with therapeutic delay ≥ 10 years. With a therapeutic delay of > 1 year, 74% had no tumor, and 25% had a tumor; with a therapeutic delay of > 10 years, 65% had no tumor and 35% had a malignancy. Among patients who had no malignancy, 64% had a therapeutic delay of < 10 years, and 36% had a therapeutic delay of ≥ 10 years. Among patients with malignancy, 47% of subjects had a therapeutic delay < 10 years, and 53% a therapeutic delay ≥ 10 years.

Conclusions

The observation of clinical characteristics of our patients with CVID may suggest that an early institution of IgG replacement therapy could be of benefit for the prevention of malignant complications.

Name of the registry: Comitato Etico Regionale delle Marche. Trial registration number: 1505. Date of registration: 27/10/2016, Retrospectively registered URL of trial registry record: http://www.ospedaliriuniti.marche.it/portale/archivio13_cerm-ancona_0_446_1.html. The trial was not registered before the first participant was enrolled
Atypical parkinsonism and intrathecal anti-glutamic acid decarboxylase antibodies – an unusual association: a case report
Authors: Stefanoni Giovanni , Formenti Anna , Tremolizzo Lucio , Stabile Andrea , Appollonio Ildebrando , Ferrarese Carlo
Published: June 2020

Background

Immunological causes of parkinsonism are very rare and usually characterized by early presentation, poor response to levodopa, and additional clinical features.

Case presentation

We describe a 58-year-old white man who presented with a 1-year history of gait disturbance with disequilibrium leading to falls. We report an association between parkinsonism and presence of anti-glutamic acid decarboxylase antibodies in his cerebrospinal fluid, discussing clinical presentation and follow-up.

Conclusions

Besides the possibility of a casual association, this case allows us to hypothesize an alternative pathophysiological mechanism of parkinsonism implying interference with glutamic acid decarboxylase and gamma-aminobutyric acid functions, eventually resulting in basal ganglia circuit dysregulation.
Extracellular vesicles produced by bone marrow mesenchymal stem cells attenuate renal fibrosis, in part by inhibiting the RhoA/ROCK pathway, in a UUO rat model
Authors: Shi Zhengzhou , Wang Qi , Zhang Youbo , Jiang Dapeng
Published: June 2020

Background

Extracellular vesicles produced by bone marrow mesenchymal stem cells (BMSC-EVs) can play important roles in the repair of injured tissues. Though numerous studies have reported the effect of EVs on renal fibrosis, the underlying mechanisms remain unclear. We hypothesized that BMSC-EVs containing milk fat globule–epidermal growth factor–factor 8 (MFG-E8) could attenuate renal fibrosis by inhibiting the RhoA/ROCK pathway.

Methods

We investigated whether BMSC-EVs have anti-fibrotic effects in a rat model of renal fibrosis, in which rats were subjected to unilateral ureteral obstruction (UUO), as well as in cultured HK2 cells. Extracellular vesicles from BMSCs were collected and co-cultured with HK2 cells during transforming growth factor-β1 (TGF-β1) treatment. HK2 cells co-cultured with TGF-β1 were also treated with the ROCK inhibitor, Y-27632.

Results

Compared with the Sham group, UUO rats displayed fibrotic abnormalities, accompanied by an increased expression of α-smooth muscle actin and Fibronectin and reduced expression of E-cadherin. These molecular and pathological changes suggested increased inflammation in damaged kidneys. Oxidative stress, as evidenced by an increased level of MDA and decreased levels of SOD1 and Catalase, was also observed in UUO kidneys. Additionally, activation of cleaved caspase-3 and PARP1 and increased apoptosis in the proximal tubules confirmed tubular cell apoptosis in the UUO group. All of these phenotypes exhibited by UUO rats were suppressed by treatment with BMSC-EVs. However, the protective effect of BMSC-EVs was completely abolished by the inhibition of MFG-E8. Consistent with the in vivo results, treatment with BMSC-EVs reduced inflammation, oxidative stress, apoptosis, and fibrosis in HK-2 cells stimulated with TGF-β1 in vitro. Interestingly, treatment with Y-27632 protected HK-2 cells against inflammation and fibrosis, although oxidative stress and apoptosis were unchanged.

Conclusions

Our results show that BMSC-EVs containing MFG-E8 attenuate renal fibrosis in a rat model of renal fibrosis, partly through RhoA/ROCK pathway inhibition.
Translational strategy using multiple nuclear imaging biomarkers to evaluate target engagement and early therapeutic efficacy of SAR439859, a novel selective estrogen receptor degrader
Authors: Besret Laurent , d’Heilly Sébastien , Aubert Cathy , Bluet Guillaume , Gruss-Leleu Florence , Le-Gall Françoise , Caron Anne , Andrieu Laurent , Vincent Sylvie , Shomali Maysoun , Bouaboula Monsif , Voland Carole , Ming Jeffrey , Roy Sébastien , Rao Srinivas , Carrez Chantal , Jouannot Erwan
Published: June 2020

Purpose

Preclinical in vivo nuclear imaging of mice offers an enabling perspective to evaluate drug efficacy at optimal dose and schedule. In this study, we interrogated sufficient estrogen receptor occupancy and degradation for the selective estrogen receptor degrader (SERD) compound SAR439859 using molecular imaging and histological techniques.

Material and methods

[18F]FluoroEstradiol positron emission tomography (FES-PET), [18F]FluoroDeoxyGlucose (FDG) PET, and [18F]FluoroThymidine (FLT) PET were investigated as early pharmacodynamic, tumor metabolism, and tumor proliferation imaging biomarkers, respectively, in mice bearing subcutaneous MCF7-Y537S mutant ERα+ breast cancer model treated with the SERD agent SAR439859. ER expression and proliferation index Ki-67 were assessed by immunohistochemistry (IHC). The combination of palbociclib CDK 4/6 inhibitor with SAR439859 was tested for its potential synergistic effect on anti-tumor activity.

Results

After repeated SAR439859 oral administration over 4 days, FES tumoral uptake (SUVmean) decreases compared to baseline by 35, 57, and 55% for the 25 mg/kg qd, 12.5 mg/kg bid and 5 mg/kg bid treatment groups, respectively. FES tumor uptake following SAR439859 treatment at different doses correlates with immunohistochemical scoring for ERα expression. No significant difference in FDG uptake is observed after SAR439859 treatments over 3 days. FLT accumulation in tumor is significantly decreased when palbociclib is combined to SAR439859 (− 64%) but not different from the group dosed with palbociclib alone (− 46%). The impact on proliferation is corroborated by Ki-67 IHC data for both groups of treatment.

Conclusions

In our preclinical studies, dose-dependent inhibition of FES tumoral uptake confirmed target engagement of SAR439859 to ERα. FES-PET thus appears as a relevant imaging biomarker for measuring non-invasively the impact of SAR439859 on tumor estrogen receptor occupancy. This study further validates the use of FLT-PET to directly visualize the anti-proliferative tumor effect of the palbociclib CDK 4/6 inhibitor alone and in combination with SAR439859.
Radii problems for some classes of analytic functions associated with Legendre polynomials of odd degree
Authors: Ebadian Ali , Cho Nak Eun , Analouei Adegani Ebrahim , Bulut Serap , Bulboacă Teodor
Published: June 2020

The aim of the present paper is to study radii problems for two general classes including various known subclasses of analytic functions associated with the normalized form of Legendre polynomials of odd degree. We also obtain some special cases of the main results presented here with some useful examples.
Approximation of functions in generalized Zygmund class by double Hausdorff matrix
Authors: Nigam H. K. , Mursaleen M. , Rani Supriya
Published: June 2020

In the present work, we emphasize, for the first time, the error estimation of a two-variable function $g(y,z)$
g
(
y
,
z
)
in the generalized Zygmund class $Y_{r}^{(\xi )}$

Y
r

(
ξ
)

($r\geq 1$
r
≥
1
) using the double Hausdorff matrix means of its double Fourier series. In fact, in this work, we establish two theorems on error estimation of a two-variable function of g in the generalized Zygmund class.
A new approach to interval-valued inequalities
Authors: Younus Awais , Asif Muhammad , Alzabut Jehad , Ghaffar Abdul , Nisar Kottakkaran Sooppy
Published: June 2020

The objective of this work is to advance and simplify the notion of Gronwall’s inequality. By using an efficient partial order and concept of gH-differentiability on interval-valued functions, we investigate some new variants of Gronwall type inequalities on time scales.
Commentary on substance use disorders and risk of suicide in a general US population: a case control study by Lynch et al.
Authors: Little Virna , James Mary Crawford
Published: June 2020

In response to the findings of the Lynch et al. study on the association of suicide mortality and substance use disorder, this commentary addresses the need for increased suicide assessment and screening for patients who identify with substance use disorders in health settings such as primary care practices and emergency departments. Lynch et al. found that all categories of substance use disorders were associated with increased risk of suicide. We present the Suicide Safer Care project as one model to address this need. The Suicide Safer Care project contains a training model that provides education on basic principles of suicide prevention and skills for integration into practice. Data collected from pre- and post-training surveys of participants demonstrates the success of the training in increasing knowledge and confidence in identification and treatment of patients at risk of suicide. Utilizing training techniques such as Suicide Safer Care and combining it with the findings from Lynch et al. providers in primary care settings and emergency departments can optimize the number of patients they identify with suicide risk, impacting the number of patients who receive treatment and the number of potential lives saved.
Choosing internet-based treatment for problematic alcohol use—why, when and how? Users’ experiences of treatment online
Authors: Ekström Veronica , Johansson Magnus
Published: June 2020

Background

Internet-based treatment has emerged as a cost-effective option for reaching people who for different reasons are not reached by traditional treatment. Internet-based treatment for problematic alcohol use, specifically, has been found to show results on par with other forms of treatment. However, in-depth knowledge of users’ experiences is required to understand what works, and what needs further development. The aim of this study is to investigate the help-seeking motives among users of an internet-based service for problematic alcohol use, as well as the users’ experiences of the support available through the service.

Method

The study consists of a thematic analysis of interviews with 38 former users of the internet-based intervention Alkoholhjälpen.

Results

The analysis shows that health and relationship factors, as well as feelings of shame, were important motives for the users’ decisions to reduce their drinking. Availability and anonymity seem to have been important reasons for choosing internet-based support. The different treatment components, i.e. ICBT program, therapist support and discussion forum, were each perceived as helpful by some users but not by others. Treatment components were described as more useful when users were able to personally identify with the content, and when it helped them reflect on their own alcohol consumption.

Conclusions

There are several aspects that are relevant, beyond the comparison between components, if we want to understand what works and for whom in internet-based treatment. Internet-based treatment services should be generous in terms of options for the users.
Growth of micro and small scale enterprises and its driving factors: empirical evidence from entrepreneurs in emerging region of Ethiopia
Authors: Meressa Hayelom Abrha
Published: June 2020

Purpose

The purpose of this study was to examine micro and small scale enterprises’ growth determinants operating in Benishangul-Gumuz Regional State of Ethiopia as emerging region.

Design/methodology/approach

The study adopted an explanatory research design with arrangement of primary data collection via a cross-sectional survey questionnaire followed by mixed research approach. The sample of this study was 220 enterprises determined by Yamane’s formula and selected using proportional stratified random sampling technique.

Findings

The result of regression analysis revealed that initial investment, access to land, access to finance, location, sectoral engagement, market linkage, and business experience are significant in explaining growth in one hand. On the other side, however, gender, education, ownership, formal recording, and financial management practice are found to be insignificant variables in determining enterprises’ growth.

Research limitations/implications

More evidence is needed on micro and small scale enterprises’ growth determinants before any generalization of the results can be made. In addition, the empirical tests were conducted only on 220 entrepreneurs since 2018. Therefore, the results of the study cannot be assumed to extend beyond this group of entrepreneurs to different study periods.

Practical implications

The study might help the entrepreneurs in addressing the factors affecting growth to take actions toward developing their performance and in turn contribute to employment, export participation, poverty alleviation, and women empowerment.

Originality/value

This paper adds to the literature on the determinants of micro- and small-scale enterprises’ growth. In particular, it tests the impact of initial investment, access to land, access to finance, location, sectoral engagement, market linkage, business experience, education, ownership structure, and financial management practice on growth of enterprises.
Reservoirs of antimicrobial resistance genes in retail raw milk
Authors: Liu Jinxin , Zhu Yuanting , Jay-Russell Michele , Lemay Danielle G. , Mills David A.
Published: June 2020

Background

It has been estimated that at least 3% of the USA population consumes unpasteurized (raw) milk from animal sources, and the demand to legalize raw milk sales continues to increase. However, consumption of raw milk can cause foodborne illness and be a source of bacteria containing transferrable antimicrobial resistance genes (ARGs). To obtain a comprehensive understanding of the microbiome and antibiotic resistome in both raw and processed milk, we systematically analyzed 2034 retail milk samples including unpasteurized milk and pasteurized milk via vat pasteurization, high-temperature-short-time pasteurization, and ultra-pasteurization from the United States using complementary culture-based, 16S rRNA gene, and metagenomic sequencing techniques.

Results

Raw milk samples had the highest prevalence of viable bacteria which were measured as all aerobic bacteria, coliform, and Escherichia coli counts, and their microbiota was distinct from other types of milk. 16S rRNA gene sequencing revealed that Pseudomonadaceae dominated raw milk with limited levels of lactic acid bacteria. Among all milk samples, the microbiota remained stable with constant bacterial populations when stored at 4 °C. In contrast, storage at room temperature dramatically enriched the bacterial populations present in raw milk samples and, in parallel, significantly increased the richness and abundance of ARGs. Metagenomic sequencing indicated raw milk possessed dramatically more ARGs than pasteurized milk, and a conjugation assay documented the active transfer of blaCMY-2, one ceftazidime resistance gene present in raw milk-borne E. coli, across bacterial species. The room temperature-enriched resistome differed in raw milk from distinct geographic locations, a difference likely associated with regionally distinct milk microbiota.

Conclusion

Despite advertised “probiotic” effects, our results indicate that raw milk microbiota has minimal lactic acid bacteria. In addition, retail raw milk serves as a reservoir of ARGs, populations of which are readily amplified by spontaneous fermentation. There is an increased need to understand potential food safety risks from improper transportation and storage of raw milk with regard to ARGs.
Treatment of coronavirus disease 2019 in Shandong, China: a cost and affordability analysis
Authors: Li Xue-Zheng , Jin Feng , Zhang Jian-Guo , Deng Yun-Feng , Shu Wei , Qin Jing-Min , Ma Xin , Pang Yu
Published: June 2020

Background

Coronavirus disease 2019 (COVID-19) is now a global public threat. Given the pandemic of COVID-19, the economic impact of COVID-19 is essential to add value to the policy-making process. We retrospectively conducted a cost and affordability analysis to determine the medical costs of COVID-19 patients in China, and also assess the factors affecting their costs.

Methods

This analysis was retrospectively conducted in Shandong Provincial Chest Hospital between 24 January and 16 March 2020. The total direct medical expenditures were analyzed by cost factors. We also assessed affordability by comparing the simulated out-of-pocket expenditure of COVID-19 cases relative to the per capita disposable income. Differences between groups were tested by student t test and Mann-Whitney test when appropriate. A multiple logistic regression model was built to determine the risk factors associated with high cost.

Results

A total of 70 COVID-19 patients were included in the analysis. The overall mean cost was USD 6827 per treated episode. The highest mean cost was observed in drug acquisition, accounting for 45.1% of the overall cost. Total mean cost was significantly higher in patients with pre-existing diseases compared to those without pre-existing diseases. Pre-existing diseases and the advanced disease severity were strongly associated with higher cost. Around USD 0.49 billion were expected for clinical manage of COVID-19 in China. Among rural households, the proportions of health insurance coverage should be increased to 70% for severe cases, and 80% for critically ill cases to avoid catastrophic health expenditure.

Conclusions

Our data demonstrate that clinical management of COVID-19 patients incurs a great financial burden to national health insurance. The cost for drug acquisition is the major contributor to the medical cost, whereas the risk factors for higher cost are pre-existing diseases and severity of COVID-19. Improvement of insurance coverage will need to address the barriers of rural patients to avoid the occurrence of catastrophic health expenditure.
RBM45 associates with nuclear stress bodies and forms nuclear inclusions during chronic cellular stress and in neurodegenerative diseases
Authors: Collins Mahlon , Li Yang , Bowser Robert
Published: June 2020

The RNA binding protein (RBP) RBM45 forms nuclear and cytoplasmic inclusions in neurons and glia in amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration with TDP-43 proteinopathy (FTLD-TDP), and Alzheimer’s disease (AD). The normal functions of RBM45 are poorly understood, as are the mechanisms by which it forms inclusions in disease. To better understand the normal and pathological functions of RBM45, we evaluated whether the protein functions via association with several membraneless organelles and whether such an association could promote the formation of nuclear RBM45 inclusions. Under basal conditions, RBM45 is diffusely distributed throughout the nucleus and does not localize to membraneless organelles, including nuclear speckles, Cajal bodies, or nuclear gems. During cellular stress, however, nuclear RBM45 undergoes a reversible, RNA-binding dependent incorporation into nuclear stress bodies (NSBs). Chronic stress leads to the persistent association of RBM45 with NSBs and the irreversible accumulation of nuclear RBM45 inclusions. We also quantified the cell type- and disease-specific patterns of RBM45 pathology in ALS, FTLD-TDP, and AD. RBM45 nuclear and cytoplasmic inclusions are found in both neurons and glia in ALS, FTLD-TDP, and AD but are absent in non-neurologic disease controls. Across neurodegenerative diseases, RBM45 nuclear inclusion pathology occurs more frequently than cytoplasmic RBM45 inclusion pathology and exhibits cell type-specific variation. Collectively, our results define new stress-associated functions of RBM45, a mechanism for nuclear RBM45 inclusion formation, a role for NSBs in the pathogenesis of ALS, FTLD-TDP, and AD, and further underscore the importance of protein self-association to both the normal and pathological functions of RBPs in these diseases.
Ongoing 5-year+ survival after multiple metastasectomies, followed by CAPOX plus bevacizumab, for metastatic colorectal cancer
Authors: Matsuishi Kozue , Miyamoto Yuji , Hiyoshi Yukiharu , Tokunaga Ryuma , Imai Katsunori , Hayashi Hiromitsu , Yamashita Yoichi , Yoshida Naoya , Baba Hideo
Published: June 2020

Background

Advancements in chemotherapy for metastatic colorectal cancer (mCRC) have improved long-term outcomes, and median survival currently exceeds 30 months. The recommended treatment for mCRC is multidisciplinary, including a combination of surgical resection and chemotherapy. In this study, we report the case of a patient who has survived for more than 5 years after an initial diagnosis of mCRC while undergoing first-line chemotherapy and six repeat metastasectomies.

Case presentation

A 55-year-old man was diagnosed at our hospital with sigmoid colon cancer and hepatic metastasis. We performed laparoscopic sigmoidectomy and hepatic segmentectomy (segment 5 [S5] and S8). After resecting the primary tumor and liver metastasis, other metastases were found. Together with perioperative chemotherapy (CAPOX + bevacizumab), we performed repeated metastasectomies for liver metastasis (S4 and S7), pulmonary S1 metastasis, aortic lymph node metastasis, and right adrenal metastasis. With six metastasectomies, the patient has survived for more than 5.5 years.

Conclusions

Multidisciplinary treatment extends survival and improves the quality of life in patients with mCRC. Planned surveillance after metastasectomy may also be necessary to promote the early detection of recurrence in these patients.
A case of small cell neuroendocrine carcinoma of the ampulla of Vater
Authors: Ito Hiroharu , Wada Yoshiyuki , Takami Yuko , Ryu Tomoki , Ureshino Hiroki , Imamura Hajime , Sasaki Shin , Ohno Akihisa , Hijioka Masayuki , Kaku Toyoma , Kawabe Ken , Kawauchi Shigeto , Saitsu Hideki
Published: June 2020

Background

Gastroenteric neuroendocrine carcinomas (NECs) account for 6.2% of gastroenteric neuroendocrine tumors (NETs), and only 1% or less of gastroenteric NETs occur in the ampulla of Vater (AoV). Clinical features of NEC of the AoV remain obscure.

Case presentation

A 65-year-old man visited a general practitioner because of jaundice, and an abdominal contrast-enhanced computed tomography scan revealed a tumor of 11 mm in diameter, which was enhanced in the arterial phase at the duodenal papilla, with dilation of the upstream bile duct. Gastrointestinal scope revealed an unexposed tumor of the AoV. Based on a biopsy of the site, a moderately differentiated tubular adenocarcinoma was suspected, and pancreatoduodenectomy was performed. Histopathological examination revealed dysplasia and highly proliferative small tumor cells, with solid and nodular formation at the AoV. Histological analysis showed a high mitotic count, and immunohistochemical staining revealed a Ki-67 index of 40–50% and cells positive for synaptophysin, chromogranin A, and p53. Small cell-type NEC was finally diagnosed. Four months post pancreatoduodenectomy, multiple liver metastases developed, and systemic chemotherapy was administered. Salvage liver resection for liver metastases was performed 14 months after the pancreatoduodenectomy. Unfortunately, multiple liver metastases developed 2 months after liver resection, and the patient died 18 months after the pancreatoduodenectomy.

Conclusions

Neuroendocrine carcinoma originating from the bile duct is very rare; therefore, in this article, we provide a review of the literature and a case report.
Nondegenerated cystic neuroendocrine tumor of the pancreas: a case report
Authors: Noda Keisuke , Kuroki Tamotsu , Yamashita Mampei , Hirayama Takanori , Natsuda Koji , Kobayashi Shinichiro , Tokunaga Takayuki , Yamanouchi Kosho , Takeshita Hiroaki , Miura Shiro , Maeda Shigeto
Published: June 2020

Background

Pancreatic neuroendocrine tumors (PNETs) are typically solid neoplasms but, in very rare cases, present as cystic lesions. We describe a case of a cystic neuroendocrine tumor that developed as a small cystic lesion.

Case presentation

In 2011, a 66-year-old Japanese woman underwent computed tomography (CT) that revealed a cystic lesion in the tail of the pancreas measuring 9 mm. She did not have any symptoms. She underwent a CT scan every year thereafter. The cystic lesion gradually increased and was 40 mm in 2019; endoscopic retrograde pancreatography (ERP) was then performed. Cytological examination demonstrated class IIIb adenocarcinoma, and we conducted laparoscopic distal pancreatectomy. Pathological examination showed PNET.

Conclusion

Although cystic change of PNET is generally caused by ischemia or necrosis inside the tumor, in our case, PNET occurred as a small cyst that increased without changing form.
Multilevel governance in trouble: the implementation of asylum seekers’ reception in Italy as a battleground
Authors: Campomori Francesca , Ambrosini Maurizio
Published: June 2020

The reception of asylum seekers in Italy has become an increasingly contentious issue: many actors, public and private, are involved at various levels of government, and cooperative behaviour cannot be taken for granted. The multi-level governance approach sheds light on the possible patterns in vertical relations, while it does not effectively explore the horizontal relations, which are however crucial, especially at the local level. Moreover, we argue that the definition of multilevel governance as negotiated order among public and non-public actors is too rigid and normative. Local policies of reception are instead a playing field where different actors come together with different interests, values and frames. This paper discusses the implementation of asylum seekers’ reception in Italy, looking at both the multilevel and the horizontal dynamics, and it uses the concept of ‘battleground’ in order better to grasp the complexities of the interaction between actors. The article discloses conflicting and competing frames between different tiers of governance, since municipalities try to resist government imposition related to asylum seekers’ reception in their areas. As for the horizontal dynamics, this paper argues that four possible patterns emerge in the relation between state and state actors: a) closure vs. civil society activism; b) tolerance; c) institutional activism vs. anti-immigrant mobilizations; d) cooperation. Overall, the paper aims at addressing the limits of the MLG approach by means of a conceptual tool (the “battleground”) which yields a more vivid understanding of implementation dynamics.
A design process for a 3D printed patient-specific applicator for HDR brachytherapy of the orbit
Authors: Subashi Ergys , Jacobs Corbin , Hood Rodney , Kirsch David G. , Craciunescu Oana
Published: June 2020

Background

This report describes a process for designing a 3D printed patient-specific applicator for HDR brachytherapy of the orbit.

Case presentation

A 34-year-old man with recurrent melanoma of the orbit was referred for consideration of re-irradiation. An applicator for HDR brachytherapy was designed based on the computed tomography (CT) of patient anatomy. The body contour was used to generate an applicator with a flush fit against the patient’s skin while the planning target volume (PTV) was used to devise channels that allow for access and coverage of the tumor bed. An end-to-end dosimetric test was devised to determine feasibility for clinical use. The applicator was designed to conform to the volume and contours inside the orbital cavity. Support wings placed flush with the patient skin provided stability and reproducibility, while 16 source channels of varying length were needed for sufficient access to the target. A solid sheath, printed as an outer support-wall for each channel, prevented bending or accidental puncturing of the surface of the applicator.

Conclusions

Quality assurance tests demonstrated feasibility for clinical use. Our experience with available 3D printing technology used to generate an applicator for the orbit may provide guidance for how materials of suitable biomechanical and radiation properties can be used in brachytherapy.
A case of anti-LGI-1 encephalitis presented as acute psychosis
Authors: Reyazuddin Mohammed , Shaan Faisal , Azmi S. A.
Published: June 2020

Anti-leucine-rich glioma inactivated protein-1 (LGI-1) encephalitis is a rare autoimmune disease with a varied neuropsychiatric clinical manifestation and have potential for reversal with immunotherapy. Early identification and treatment are therefore of paramount importance. We present the case of a 43-year-old man admitted for acute psychosis with facio-brachial dystonic seizures not responding to anti-epileptic drugs (AEDs). His symptoms started approximately 5 months prior admission to the hospital and associated with progressive cognitive impairment (particularly verbal and visio-spatial domains) followed by altered behavior, irrelevant talk, and disturbance in daily activities of living and facio-brachial dystonic seizures. There was history of allergic reaction to valproate, carbamazepine and levetiracetam, and serum sample tested strongly positive for LGI-1 (leucine rich glioma inactivated-1) antibodies. He was treated with injection methylprednisolone (1 gm intravenous) brief pulse therapy for 7 days and then underwent four sessions of plasma exchange followed by oral steroids and immunosuppressant therapy. Treatment was successful and patient returned to his previous baseline functioning but patient develops steroid induced hypomania and diabetes mellitus in the due course of time. Patient was discharged after successful resolution of symptoms. Patient did not come up for follow-up. He was contacted telephonically and we get to know that he relapsed after 2 weeks and consulted at higher center where he died while on treatment. Prognosis of anti-LGI-1 encephalitis is usually good but our patient died.
Emotional intelligence in bipolar-I-disorder: A comparison between patients, unaffected siblings, and control subjects
Authors: Frajo-Apor Beatrice , Kemmler Georg , Pardeller Silvia , Huber Markus , Macina Christian , Welte Anna-Sophia , Hoertnagl Christine , Hofer Alex
Published: June 2020

Background.

Impairments in social and nonsocial cognition have been demonstrated in both patients suffering from bipolar disorder (BD) and their unaffected relatives and might therefore represent a heritable marker of risk. This study investigated the relevance of emotional intelligence (EI) as part of the emotion processing domain of social cognition in this regard.

Methods.

A total of 54 outpatients suffering from BD, 54 unaffected siblings, and 80 control subjects were investigated using the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) and the Brief Assessment of Cognition in Schizophrenia (BACS). Analyses of covariance (ANCOVAs) were performed with adjustment for the BACS composite score. The three groups were compared by one-way analysis of variance or chi-square test, depending on the variable type. As the three groups differed significantly in their level of education, additional ANCOVAs with adjustment for education were performed.

Results.

Patients achieved significantly lower levels of overall EI and overall nonsocial cognitive functioning compared to unaffected siblings and controls, whereas performance of the latter two groups was comparable in both domains.

Conclusions.

Due to comparable levels of EI in unaffected siblings of patients suffering from BD and control subjects, EI assessed by means of the MSCEIT does not represent an endophenotype for BD.
Quantified Kinematics to Evaluate Patient Chemotherapy Risks in Clinic
Authors: Hasnain Zaki , Nilanon Tanachat , Li Ming , Mejia Aaron , Kolatkar Anand , Nocera Luciano , Shahabi Cyrus , Cozzens Philips Frankie A. , Lee Jerry S.H. , Hanlon Sean E. , Vaidya Poorva , Ueno Naoto T. , Yennu Sriram , Newton Paul K. , Kuhn Peter , Nieva Jorge
Published: June 2020

PURPOSE

Performance status (PS) is a key factor in oncologic decision making, but conventional scales used to measure PS vary among observers. Consumer-grade biometric sensors have previously been identified as objective alternatives to the assessment of PS. Here, we investigate how one such biometric sensor can be used during a clinic visit to identify patients who are at risk for complications, particularly unexpected hospitalizations that may delay treatment or result in low physical activity. We aim to provide a novel and objective means of predicting tolerability to chemotherapy.

METHODS

Thirty-eight patients across three centers in the United States who were diagnosed with a solid tumor with plans for treatment with two cycles of highly emetogenic chemotherapy were included in this single-arm, observational prospective study. A noninvasive motion-capture system quantified patient movement from chair to table and during the get-up-and-walk test. Activity levels were recorded using a wearable sensor over a 2-month period. Changes in kinematics from two motion-capture data points pre- and post-treatment were tested for correlation with unexpected hospitalizations and physical activity levels as measured by a wearable activity sensor.

RESULTS

Among 38 patients (mean age, 48.3 years; 53% female), kinematic features from chair to table were the best predictors for unexpected health care encounters (area under the curve, 0.775 ± 0.029) and physical activity (area under the curve, 0.830 ± 0.080). Chair-to-table acceleration of the nonpivoting knee ( t = 3.39; P = .002) was most correlated with unexpected health care encounters. Get-up-and-walk kinematics were most correlated with physical activity, particularly the right knee acceleration ( t = −2.95; P = .006) and left arm angular velocity ( t = −2.4; P = .025).

CONCLUSION

Chair-to-table kinematics are good predictors of unexpected hospitalizations, whereas the get-up-and-walk kinematics are good predictors of low physical activity.
The Affordable Care Act's Missing Consensus: Values, Attitudes, and Experiences Associated with Competing Health Reform Preferences
Authors: McIntyre Adrianna , Blendon Robert J. , Benson John M. , Findling Mary G. , Schneider Eric C.
Published: June 2020

Ten years after its enactment, public support for the Affordable Care Act (ACA) still only reaches a scant majority. Candidates for the presidency—and the sitting president—have endorsed health reforms that would radically transition US health care away from the current system upon which the ACA was built. Few opinion surveys to date have captured dominant preferences among alternative health reform policies or characterized attitudes and experiences that might be associated with policy preferences. Using a 2019 nationally representative telephone survey, this article considers how variations in political values, attitudes toward government, and experiences with the health care system relate to competing health reform preferences. Differences between those who favor Medicare for All over building on the ACA largely reflect different levels of satisfaction with the status quo and views of private health insurance. By contrast, differences between ACA supporters and those who would favor replacing it with a state-based alternative reflect sharply different political values and attitudes. Key differences remain significant after controlling for demographic, health, and political characteristics. Overwhelming public support still eludes the ACA, and reaching consensus on future directions for health reform will remain challenging given differences in underlying beliefs.
Patient-Reported Outcome Measures for Post-mastectomy Breast Reconstruction: A Systematic Review of Development and Measurement Properties
Authors: Davies C. F. , Macefield R. , Avery K. , Blazeby J. M. , Potter S.
Published: June 2020

Background

Breast reconstruction (BR) is performed to improve outcomes for patients undergoing mastectomy. A recently developed core outcome set for BR includes six patient-reported outcomes that should be measured and reported in all future studies. It is vital that any instrument used to measure these outcomes as part of a core measurement set be robustly developed and validated so data are reliable and accurate. The aim of this systematic review is to evaluate the development and measurement properties of existing BR patient-reported outcome measures (PROMs) to inform instrument selection for future studies.

Methods

A PRISMA-compliant systematic review of development and validation studies of BR PROMs was conducted to assess their measurement properties. PROMs with adequate content validity were assessed using three steps: (1) the methodological quality of each identified study was assessed using the COSMIN Risk of Bias checklist; (2) criteria were applied for assessing good measurement properties; and (3) evidence was summarized and the quality of evidence assessed using a modified GRADE approach.

Results

Fourteen articles reported the development and measurement properties of six PROMs. Of these, only three (BREAST-Q, BRECON-31, and EORTC QLQ-BRECON-23) were considered to have adequate content validity and proceeded to full evaluation. This showed that all three PROMs had been robustly developed and validated and demonstrated adequate quality.

Conclusions

BREAST-Q, BRECON-31, and EORTC QLQ-BRECON-23 have been well-developed and demonstrate adequate measurement properties. Work with key stakeholders is now needed to generate consensus regarding which PROM should be recommended for inclusion in a core measurement set.
Land Reform and Productivity: A Quantitative Analysis with Micro Data
Authors: Adamopoulos Tasso , Restuccia Diego
Published: June 2020

We assess the effects of a major land policy change on farm size and agricultural productivity using a quantitative model and micro-level data. We study the 1988 land reform in the Philippines that imposed a ceiling on land holdings, redistributed above-ceiling lands to landless and smallholder households, and severely restricted the transferability of the redistributed farmlands. We study this reform in the context of an industry model of agriculture with a nondegenerate distribution of farm sizes featuring an occupation decision and a technology choice of farm operators. In this model, the land reform can reduce agricultural productivity not only by misallocating resources across farmers but also by distorting farmers’ occupation and technology decisions. The model, calibrated to prereform farm-level data in the Philippines, implies that on impact, the land reform reduces average farm size by 34 percent and agricultural productivity by 17 percent. The government assignment of land and the ban on its transfer are key for the magnitude of the results since a market allocation of the above-ceiling land produces about one-third of the size and productivity effects. These results emphasize the potential role of land market efficiency for misallocation and productivity in the agricultural sector. (JEL D24, O11, O13, Q12, Q15, Q18, Q24, Q28)
Liquidity and Consumption: Evidence from Three Post-Earthquake Reconstruction Programs in Italy
Authors: Acconcia Antonio , Corsetti Giancarlo , Simonelli Saverio
Published: June 2020

In Italian regions hit by earthquakes, homeowners typically receive public funds to finance reconstruction. While these funds are strictly tied to reconstruction work, they are in part disbursed up front, leading to significant variation in cash on hand. We exploit this variation to study the effects of liquidity on relatively wealthy households’ consumption. We find a large and significant response in the first year that homeowners receive the cash and provide evidence that this response is driven by illiquid households with bank debt. Instead, we find no evidence that consumption responds to funds paid directly to firms, thus leaving households’ liquidity unaffected. (JEL E21, G51, H76, Q54, R31)