bluuebunny/crossref_metadata_2025 huggingface dataset:
A case–control study of agricultural and behavioral factors associated with leptospirosis in Vietnam
Authors: Dung Luu Phuong , Hai Pham Thanh , Hoa Luong Minh , Mai Tran Ngoc Phuong , Hanh Nguyen Thi My , Than Phan Dang , Tran Van Dinh , Quyet Nguyen Tu , Hai Hoang , Ngoc Do Bich , Thu Nguyen Thị , Mai Le Thi Phuong
Published: June 2022

Introduction

Leptospirosis is a neglected disease in Vietnam. Until now, there has been limited knowledge about risk factors of this disease in Vietnam. The study was carried out to identify agricultural and behavioral factors associated with the transmission of leptospirosis in Vietnam.

Methods

This matched retrospective hospital-community-based case–control study was conducted from 1 October 2018 to 31 October 2019. We recruited cases from 11 selected government hospitals in three provinces of Vietnam, while controls were selected from the same communes of cases and matched by age (± 2 years) and sex. Microscopic agglutination test (MAT) and enzyme-linked immunosorbent assay (ELISA) were applied to determine confirmed cases, while only MAT was used to identify controls with a single high MAT titer < 1:100.

Results

504 participants (252 cases and 252 controls) were identified. Cultivating (OR 2.83, CI 1.38–5.79), animal farming (OR 8.26, CI 2.24–30.52), pig owners (OR 10.48, CI 5.05–21.73), cat owners (OR 2.62, CI 1.49–4.61) and drinking unboiled water (OR 1.72, CI 1.14 –2.59, p = 0.010) were significantly associated with human leptospirosis in Vietnam. Hand washing after farming/ gardening (OR 0.57, CI 0.38–0.86, p = 0.007) and bathing after farming, gardening, contact with cattle and poultry (OR 0.33, CI 0.19–0.58, p = 0.000) were determined as protective factors for this disease.

Conclusions

In short, the case–control study has revealed the risks in agricultural and animal practices and protective behavioral factors related to human leptospirosis in Vietnam. The findings suggested promotion of communication and health education programs targeting health behaviors in daily life and agricultural practices. Using personal protective equipment such as gowns, gloves, and boots during agricultural practices, especially cultivating and animal farming, is most recommended.
Viral pathogens of acute gastroenteritis in Egyptian children: role of the parechovirus
Authors: Mashaly Mervat El-Sayed , Alkasaby Nashwa M. , Bakr Asmaa , Zaki Maysaa El Sayed , Montasser Karim
Published: June 2022

Background and aim

Human parechovirus (HPeV) has emerged as a pathogen associated with acute gastroenteritis (AGE).

Aim

To detect the presence of HPeV in the stool samples from Egyptian children with AGE seeking care and the possibility of its co-infection with other enteric viruses.

Methodology

One hundred stool samples were collected from children attending Mansoura University Children's Hospital with AGE. HPeV and astrovirus were detected by reverse transcriptase-polymerase chain reaction (RT-PCR). At the same time, detection of rotavirus antigen and norovirus was achieved by enzyme-linked immunosorbent assay and rapid immunochromatographic method, respectively.

Results

The most frequently detected virus was rotavirus (39%), followed by norovirus (27%), HPeV (19%), and astrovirus (12%). Interestingly, the single infection with HPeV was 5%. Among the 19 HPeV positive samples, the co-infection of HPeV with other enteric viruses was detected in 9(43.9%) for rotavirus, 7(36.8%) for norovirus, 2(10.5%) for astrovirus, in 3(15.8%) for rotavirus and norovirus and 1(5.3%) for norovirus and astrovirus. Regarding the clinical presentation, there was no significant difference between children infected with HPeV alone and those infected with viruses other than HPeV alone; fever (p = 0.3), vomiting (p = 0.12), abdominal pain (p = 0.12), and grades of severity (P = 0.82). HPeV alone infected children were of mild severity (60%), and their main presenting symptom was fever (60%).

Conclusions

Detection of HPeV as a single viral pathogen in the stool of some children with AGE showed that this virus could be a causative agent of AGE in Egyptian children. Therefore, HPeV could be included as one of the viruses screened for AGE diagnosis in children in Egypt.
A nomogram based on A-to-I RNA editing predicting overall survival of patients with lung squamous carcinoma
Authors: Liu Li , Liu Jun , Deng Xiaoliang , Tu Li , Zhao Zhuxiang , Xie Chenli , Yang Lei
Published: June 2022

Background

Adenosine-to-inosine RNA editing (ATIRE) is characterized as non-mutational epigenetic reprogramming hallmark of cancer, while little is known about its predictive role in cancer survival.

Methods

To explore survival-related ATIRE events in lung squamous cell carcinoma (LUSC), ATIRE profile, gene expression data, and corresponding clinical information of LUSC patients were downloaded from the TCGA database. Patients were randomly divided into a training (n = 134) and validation cohort (n = 94). Cox proportional hazards regression followed by least absolute shrinkage and selection operator algorithm were performed to identify survival-related ATIRE sites and to generate ATIRE risk score. Then a nomogram was constructed to predict overall survival (OS) of LUSC patients. The correlation of ATIRE level and host gene expression and ATIREs’ effect on transcriptome expression were analyzed.

Results

Seven ATIRE sites that were TMEM120B chr12:122215052A > I, HMOX2 chr16:4533713A > I, CALCOCO2 chr17:46941503A > I, LONP2 chr16:48388244A > I, ZNF440 chr19:11945758A > I, CLCC1 chr1:109474650A > I, and CHMP3 chr2:86754288A > I were identified to generate the risk score, of which high levers were significantly associated with worse OS and progression-free survival in both the training and validation sets. High risk-score was also associated with advanced T stages and worse clinical stages. The nomogram performed well in predicting OS probability of LUSC. Moreover, the editing of ATIRE sites exerted a significant association with expression of host genes and affected several cancer-related pathways.

Conclusions

This is the first comprehensive study to analyze the role of ATIRE events in predicting LUSC survival. The AITRE-based model might serve as a novel tool for LUSC survival prediction.
Evaluating patient data quality in South Africa’s National Health Laboratory Service Data Warehouse, 2017-2020: implications for monitoring child health programmes
Authors: Radebe Lebohang , Haeri Mazanderani Ahmad , Sherman Gayle G.
Published: June 2022

Background

South Africa’s National Health Laboratory Service (NHLS), the only clinical laboratory service in the country’s public health sector, is an important resource for monitoring public health programmes.

Objectives

We describe NHLS data quality, particularly patient demographics among infants, and the effect this has on linking multiple test results to a single patient.

Methods

Retrospective descriptive analysis of NHLS data from 1st January 2017—1st September 2020 was performed. A validated probabilistic record-linking algorithm linked multiple results to individual patients in lieu of a unique patient identifier. Paediatric HIV PCR data was used to illustrate the effect on monitoring and evaluating a public health programme. Descriptive statistics including medians, proportions and inter quartile ranges are reported, with Chi-square univariate tests for independence used to determine association between variables.

Results

During the period analysed, 485 300 007 tests, 98 217 642 encounters and 35 771 846 patients met criteria for analysis. Overall, 15.80% (n = 15 515 380) of all encounters had a registered national identity (ID) number, 2.11% (n = 2 069 785) were registered without a given name, 63.15% (n = 62 020 107) were registered to women and 32.89% (n = 32 304 329) of all folder numbers were listed as either the patient’s date of birth or unknown. For infants tested at < 7 days of age (n = 2 565 329), 0.099% (n = 2 534) had an associated ID number and 48.87% (n = 1 253 620) were registered without a given name. Encounters with a given name were linked to a subsequent encounter 40.78% (n = 14 180 409 of 34 775 617) of the time, significantly more often than the 21.85% (n = 217 660 of 996 229) of encounters registered with a baby-derivative name (p-value < 0.001).

Conclusion

Unavailability and poor capturing of patient demographics, especially among infants and children, affects the ability to accurately monitor routine health programmes. A unique national patient identifier, other than the national ID number, is urgently required and must be available at birth if South Africa is to accurately monitor programmes such as the Prevention of Mother-to-Child Transmission of HIV.
The cascade of hypertension care in Cambodia: evidence from a cross-sectional population-based survey
Authors: Chham Savina , Buffel Veerle , Van Olmen Josefien , Chhim Srean , Ir Por , Wouters Edwin
Published: June 2022

Background

Hypertension (HTN) is a leading cause of cardiovascular diseases and deaths globally. To respond to the high HTN prevalence (23.5% among adults aged 40–69 years in 2016) in Cambodia, the government (and donors) established innovative interventions to improve access to screening, care, and treatment at different public health system and community levels. We assessed the effectiveness of these interventions and resulting health outcomes through a cascade of HTN care and explored key determinants.

Methods

We performed a population-based survey among 5070 individuals aged ≥ 40 years to generate a cascade of HTN care in Cambodia. The cascade, built with conditional approach, shows the patients’ flow in the health system and where they are lost (dropped out) along the steps: (i) prevalence, (ii) screening, (iii) diagnosis, (iv) treatment in the last twelve months, (v) treatment in the last three months, and (vi) HTN being under control. The profile of people dropping out from each bar of the cascade was determined by multivariate logistic regression.

Results

The prevalence of HTN (i) among study participants was 35.2%, of which 81.91% had their blood pressure (BP) measured in the last three years (ii). Over 63.72% of those screened were diagnosed by healthcare professionals as hypertensive patients (iii). Among these, 56.19% received treatment in the last twelve months (iv) and 54.26% received follow-up treatment in the last three months (v). Only 35.8% of treated people had their BP under control (vi). Males, those aged ≥ 40 years, and from poorer households had lower odds to receive screening, diagnosis, and treatment. Lower odds to have their BP under-control were found in males, those from poor and rich quintiles, having HTN < five years, and receiving treatment at a private facility.

Conclusions

Overall, people with HTN are lost along the cascade, suggesting limited access to appropriate screening, diagnosis, and treatment and resulting poor health outcomes, especially among those who are male, aged 40–49 years, from poorer households, and visiting a private facility. Efforts to improve the quality of facility-based and community-based interventions are needed to prevent inequitable drops along the cascade of care.
Dynamic rewiring of biological activity across genotype and lineage revealed by context-dependent functional interactions
Authors: Kim Eiru , Novak Lance C. , Lin Chenchu , Colic Medina , Bertolet Lori L. , Gheorghe Veronica , Bristow Christopher A. , Hart Traver
Published: June 2022

Background

Coessentiality networks derived from CRISPR screens in cell lines provide a powerful framework for identifying functional modules in the cell and for inferring the roles of uncharacterized genes. However, these networks integrate signal across all underlying data and can mask strong interactions that occur in only a subset of the cell lines analyzed.

Results

Here, we decipher dynamic functional interactions by identifying significant cellular contexts, primarily by oncogenic mutation, lineage, and tumor type, and discovering coessentiality relationships that depend on these contexts. We recapitulate well-known gene-context interactions such as oncogene-mutation, paralog buffering, and tissue-specific essential genes, show how mutation rewires known signal transduction pathways, including RAS/RAF and IGF1R-PIK3CA, and illustrate the implications for drug targeting. We further demonstrate how context-dependent functional interactions can elucidate lineage-specific gene function, as illustrated by the maturation of proreceptors IGF1R and MET by proteases FURIN and CPD.

Conclusions

This approach advances our understanding of context-dependent interactions and how they can be gleaned from these data. We provide an online resource to explore these context-dependent interactions at diffnet.hart-lab.org.
Mantle cell lymphoma negative for t(11,14) involving the kidneys: a case report
Authors: Nassereldine Hasan , Mohty Razan , Awada Hussein , Abou Dalle Iman , El-Cheikh Jean , Bazarbachi Ali
Published: June 2022

Background

Mantle cell lymphoma is the rarest subtype of non-Hodgkin’s lymphoma. It can exhibit diverse extranodal manifestations. However, renal involvement is uncommon, and if it occurs, it usually only gets detected postmortem. There are several mechanisms by which mantle cell lymphoma can damage the kidneys. Renal failure is a potential complication, and prompt evaluation and diagnosis are critical steps to prevent long-term complications.

Case presentation

We present the case of a 75-year-old non-Hispanic White male with past medical history significant for hypertension and dyslipidemia, presenting with fever, weight loss, and night sweats. Work-up showed markedly elevated white blood cells, multiple enlarged lymph nodes, and a kidney mass. The patient was diagnosed with mantle cell lymphoma with kidney involvement confirmed with a kidney biopsy. His disease was positive for cyclin D1 overexpression despite t(11; 14) absence. The patient received six cycles of alternating vincristine, rituximab, cyclophosphamide, doxorubicin, and prednisone then dexamethasone, high-dose cytarabine, and oxaliplatin, after which he was maintained on ibrutinib and rituximab, with resolution of symptoms and disease regression.

Conclusion

We present a case of a rare presentation of Mantle cell lymphoma while describing the clinical presentation and diagnostic and treatment approaches. This case report can assist physicians in the clinical work-up and treatment of patients with similar diagnosis or presentation.
Exploring the roles of information search and information evaluation literacy and pre-service teachers’ ICT self-efficacy in teaching
Authors: Peciuliauskiene Palmira , Tamoliune Giedre , Trepule Elena
Published: June 2022

This study analyzes the relationship between pre-service teachers’ information search and information evaluation literacy and their information and communication technology (ICT) self-efficacy in teaching. Theoretical analysis confirmed a direct relation between information literacy and pre-service teachers’ ICT self-efficacy in teaching. However, there is insufficient understanding regarding the effect that specific components of information literacy, i.e., information search and evaluation, have on teachers’ ICT self-efficacy in teaching. Data were collected using an online survey of students in teacher training programs who were engaged as research participants. The analysis disclosed that perceived information evaluation literacy has a more strongly expressed indirect impact on teachers’ ICT self-efficacy than a direct impact, while perceived information search literacy has a stronger direct impact on teachers’ ICT self-efficacy in teaching. Therefore, for teacher educators, it is important to develop a sufficient level of information literacy and ensure a positive experience with information search and evaluation, which are related to higher pre-service teachers’ ICT self-efficacy in teaching. This finding may help support calls for teacher training and/or professional development programs with a focus on information literacy, which might increase teachers’ ICT self-efficacy in teaching and improve ICT use in teaching.
Green synthesis, characterization and antibacterial, antifungal, larvicidal and anti-termite activities of copper nanoparticles derived from Grewia asiatica L.
Authors: Tahir Arifa , Quispe Cristina , Herrera-Bravo Jesús , Iqbal Hafsa , ul Haq Zia , Anum Faiza , Javed Zeeshan , Sehar Anam , Sharifi-Rad Javad
Published: June 2022

Background

The current study was conducted to find out an eco-friendly and cost-efficient way to prepare copper nanoparticles (CuNPs) by utilizing Grewia asiatica L. leaf extract, which was found to be a very effective antimicrobial and larvicidal chemical.

Methods

Characterization of nanoparticles was also carried out by utilizing Fourier transform infrared spectroscopy (FTIR) analysis, scanning electron microscope along with X-ray diffraction analysis (XRD). The artificially prepared nanoparticles in the laboratory were approximately in the range of 2 µm in size and crystalline in nature. The CuNPs were tested for their antimicrobial activity against different types of fungi and bacteria, also some mosquito and termite. All the results and observations were tested with a one-way analysis of variance keeping the probability level at < 0.0001.

Results

The copper nanoparticles exhibit significant antibacterial and antifungal activities and are also found lethal for many mosquito and termite species. Antibacterial activity was checked against Escherichia coli and Bacillus subtilis, their zone of inhibition was 17 nm and 20 nm, respectively. The antifungal potential was checked against Aspergillus niger and Aspergillus oryzae and the zone of inhibition was recorded at 20 mm and 23 mm, respectively. CuNPs were also found lethal for many mosquitoes and maximum efficacy of CuNPs against Aedes aegypti larva was observed at 100 mg/ml after 24 h. Termite species such as Heterotermes indicola were exposed to CuNPs and the highest mortality rate in termites was seen at 100 ppm concentration of CuNPs. Current research provides the first investigation of CuNPs of G. asiatica as a larvicidal and as an anti-termite. G. asiatica garden-fresh leaves were collected from Railway colony Mughalpura.

Conclusions

This study proves that CuNPs have a toxic effect on insects and can also be utilized as a biological control of insects. By using such a scientific approach, the scientists can lower the costs of chemical usage and a biodegradable alternative could be provided.
Toxicological exposure to phthalates mixtures and human health risk assessment of drinking water and fruit drinks packaged in plastics and tetra pak cartons
Authors: Adegunwa Abiodun Odunlami , Adegunwa Aderibigbe Kola , Oyatoyinbo Rokeebat Motunrayo
Published: June 2022

Background

This study estimates the migration and levels of phthalate esters in drinking water and fruit drinks packed in plastics and tetra pak cartons that are regularly available for consumption in Nigeria. The probable human health risk from the long-term consistent ingestion of the drinking water and fruit drinks products were also investigated.

Results

Nine (9) phthalates were detected in the analyzed samples and they all showed varying concentrations. The results showed that the total mean concentration of the analyzed phthalates in the drinking water and fruit drinks packed in plastic container were found with the range of 1740–2370 µg/L and 1340–2220 µg/L respectively while fruit drinks packed in tetra pak container showed comparatively low concentration range of 385–450 µg/L. Also, the health hazard (HQ) values for the exposure via oral ingestion by adults were recorded at 505.974, 390.353 and 64.161 respectively for water and, fruit drinks packed in plastics and tetra pak containers. Correspondingly, very high values of HQ were observed in children (2529.80, 2187.39 and 355.92). The overall carcinogenic risks estimated owing to oral ingestion in adults were 0.01, 0.02 and 3.3 × 10–4 for drinking water and fruit drinks packaged with plastics and tetra pak container respectively while higher carcinogenic (CR) values of 0.04, 0.08 and 0.02 were observed in children.

Conclusions

The result obtained showed comparatively low concentrations of phthalates in fruits drinks packaged in Tetra Pak cartons than drinking water and fruit drinks in plastics containers. The high values of hazard index (HI) and CR observed in drinking water and fruit drink packaged in plastics is an indication of future health challenges relating to carcinogenic effects on the favorite consumer of the drinks in which children are more vulnerable. In view of this, packages like tetra pak product and less toxic materials could be adopted for packing drinking water and fruit drinks to avoid exposing consumers to phthalates present in plastics containers which have attendant negative health effect.
Cataloging targetable dependencies of head and neck cancer cell lines in the DepMap CRISPR screens.
Authors: Basu Devraj , Cao Austin , Raghav Lovely , Rajagopalan Pavithra , Brody Robert , Gimotty Phyllis A.
Published: June 2022

6056

Background: The DepMap genome-wide loss of function CRISPR screens offer new insight into gene dependencies in HPV(-) head and neck squamous cell carcinoma (HNSCC) cell lines. We aimed to leverage this data to guide preclinical studies by cataloging targetable dependencies and identifying ones predicted to offer a therapeutic window. We also aimed to identify targets representing potential synthetic lethalities by testing for associations between genetic alterations and dependency profile. Methods: DepMap was queried for gene probability and effect scores in cell lines from 77 tumors, including 62 HPV(-) HNSCCs plus 15 ESCCs, which have comparable etiology, genetic features, and tissue of origin. A probability score of ≥ 0.5 was used as the threshold for essentiality. Essential genes were selected for analysis by 3 criteria: (1) presence in ≥10% cell lines, (2) lack of dependency in CRISPR screens of normal human cell lineages, and (3) designation as druggable by the Drug-Gene Interaction Database. Gene set enrichment analysis was performed using the Hallmark Gene Sets. DepMap gene effect scores were used to prioritize targets likely to have a useful therapeutic window based on median scores greater than for EGFR (0.676), a target with established albeit modest utility for HNSCC. The Open Targets platform was used to identify targets with inhibitors used in trials for other cancers and/or nonmalignant diseases. Associations between dependencies and genetic alterations were defined using two-sample t-tests, with filter conditions of p < 0.05 and effect size ≥1. Results: The 231 genes meeting selection criteria had a median gene effect score of 0.56. The criteria captured targets of standard therapeutic agents including TYMS (5-FU), tubulin genes (paclitaxel), EGFR (cetuximab), plus known oncogenes like PIK3CA. GSEA showed enrichment of known oncogenic signaling pathways including PI3K/AKT and JAK/STAT, as well as hallmark cancer processes like DNA repair and apoptosis. 90% were not known oncogenes cataloged in the OncoKB Database. 45 genes had a median gene effect score between that of EGFR and the median for common essential genes, including 7 without known cancer-promoting roles: OTOP1, DHRSX, UTP11, MBTPS1, SLC25A3, PPIAL4G, and RBM10. 17% had inhibitors that reached a non-HNSCC phase II trial, including 10 targets not previously tested in cancer. Novel associations between dependencies and genetic alterations included DDX3X with NOTCH1mut, ITGB1 with CDKN2Amut, and ATP1A1 with HRASmut. Conclusions: We catalog targetable dependencies in cell line models of HNSCC. While well-studied targets were captured, many genes lacked known roles in malignancy. Targets of inhibitors tested in other diseases provide new tools to guide preclinical studies. Association of some dependencies with known molecular subgroups in HNSCC may enhance use of cell line models to personalize therapy.
Nivolumab-based induction chemoimmunotherapy and PD-L1 expression in locoregionally advanced HPV-associated oropharyngeal squamous cell carcinoma.
Authors: Rosenberg Ari , Pearson Alexander T. , Agrawal Nishant , Juloori Aditya , Seiwert Tanguy Y. , Gooi Zhen , Blair Elizabeth A. , Izumchenko Evgeny , Chin Jeffrey , Ginat Daniel , Lingen Mark , Haraf Daniel J. , Vokes Everett E.
Published: June 2022

6075

Background: Blockade of the PD-1/PD-L1 immune checkpoint improves survival in recurrent/metastatic head and neck cancer. PD-L1 expression is a biomarker that enriches for clinical benefit with anti-PD-1 therapy alone or in combination with chemotherapy in this setting. The role of PD-L1 expression as a predictive biomarker in locoregional human papillomavirus associated (HPV+) head and neck cancer (HNC) treated with induction nivolumab-based chemoimmunotherapy is unknown. We evaluate PD-L1 expression and response to induction chemoimmunotherapy in the context of an investigator initiated trial, OPTIMA II. Methods: Patients with locoregionally advanced HPV+ HNC were enrolled to the prospective OPTIMA II study evaluating induction chemoimmunotherapy followed by response adaptive de-escalated locoregional therapy. Induction therapy consisted of nivolumab, nab-paclitaxel, and carboplatin, for three cycles. Anatomic imaging of the head and neck with either CT or MRI was obtained at baseline and following induction therapy. Expression of PD-L1 was assessed by immunohistochemistry on baseline biopsies and calculation of tumor proportion score (TPS) and combined positive score (CPS) was performed. Response is defined as percentage of tumor shrinkage per RECIST 1.1 criteria. Deep response rate is defined as the proportion of patients with > = 50% tumor shrinkage. Kruskal-Wallis and Mann-Whitney tests were used for analysis. Results: Twenty-nine patients (pts) underwent evaluation of PD-L1 expression and started treatment with induction chemoimmunotherapy. Median age 61 (range 37-81), smoker > 20 pack years in 24%, tonsil primary in 79%, and HPV16 subtype in 97%. The median response following induction was 63% (range 29% to 100%). PD-L1 TPS scores were < 1, 1-19, and > = 20 in 28%, 34%, and 38% respectively. PD-L1 CPS scores were < 20 and > = 20 in 55% and 45% respectively. Median response among PD-L1 TPS of < 1, 1-19, and > = 20 was 49%, 59%, and 66% respectively (p = 0.16). Among PD-L1 CPS of < 20 and > = 20, median response was 57% and 69% respectively (p = 0.11). The deep response rate among PD-L1 CPS < 20 and > = 20 was 69% and 77% respectively. Conclusions: Deep responses were observed following induction chemoimmunotherapy in locoregionally advanced HPV+ HNC. There was a non-significant increase in median response and deep response rate with higher expression of PD-L1. Evaluation of PD-L1 expression as a biomarker for response with induction chemoimmunotherapy is worthy of further investigation in locoregional HPV+ disease. Clinical trial information: NCT03107182.
Circulating tumor DNA profiling and serial analysis in salivary gland carcinomas reveal unique mutational subsets and actionable alterations.
Authors: Russell Jeffery Scott , Kerrigan Kathleen Claire , Yang Dong
Published: June 2022

6097

Background: Salivary gland carcinoma is a rare head and neck malignancy without any FDA approved treatment options. ctDNA profiling has been shown to be a valuable tool in identifying novel targets and expanding potential therapeutic options. Here, we report the landscape of ctDNA in a large dataset of salivary gland carcinomas. Methods: Analysis of genomic results from blood samples with a diagnosis of salivary gland carcinoma that were prospectively collected between January 2017 to December 2021 for clinical Guardant360 testing. Histologic subtype was documented by ordering providers as available. Serial tests were defined as having Guardant360 analysis performed on more than one sample collected at more than one timepoint. Results: Among 222 patients tested with Guardant360, 59.5% were male and the median age was 64 years (range 22-93 years). Of reported diagnoses, 137 (61.7%) patients had salivary gland carcinoma NOS. The remaining samples were designated by specific salivary histology: 13 (5.9%) salivary gland mucoepidermoid carcinoma (SGMC), 19 (8.6%) salivary gland adenocarcinoma (SGA), 37 (16.7%) salivary gland adenoid cystic carcinoma (SGACC), and 16 (72%) salivary duct carcinoma (SDC). ctDNA genomic alterations (GAs) were identified in 205 (81.3%) of 252 samples. The median variant allele fraction was 0.6% (range 0.01%-46.4%). TMB was evaluated in 45 samples of which 33 were evaluable and the median and 80th percentile of TMB was 8.44 and 11.81 mut/Mb. MSI-H was not detected in any of the 181 samples tested for MSI. The most commonly altered genes were TP53, PIK3CA, ERBB2, ATM, EGFR and HRAS across all collected salivary samples. Further analysis stratified genetic alterations by tissue subtype. Other than TP53, common mutations by salivary gland carcinoma subtype included: PI3KCA (SGACC/SDC), ERBB2 (SGA), and EGFR (SGMC). In regards to serial analysis, 16 patients had at least 2 serial tests. When comparing the subsequent testing within the same patient, 3 patients had potentially new actionable GAs (including BRAF, KRAS mutations and EGFR amplification) on the subsequent test that were not identified on the original test. Conclusions: Blood-based liquid biopsy can be applied in salivary gland tumors to detect genomic alterations in ctDNA which may provide opportunities for therapeutic intervention in a cancer with limited treatment options. Additionally, ctDNA testing may be used to identify resistant alterations to potential therapy. Finally, longitudinal assessment of ctDNA may shed light on tumor evolution and additional therapeutic targets may be found. Further assessment of serial ctDNA analysis and the potential impact on patient clinical outcomes needs to be elucidated.
Variants of SLC2A10 may be Linked to Poor Response to Metformin
Authors: Paz-Pacheco Elizabeth , Nevado Jose B , Cutiongco-de la Paz Eva Maria C , Jasul Gabriel V , Aman Aimee Yvonne Criselle L , Ribaya Elizabeth Laurize A , Francisco Mark David G , Guanzon Ma Luz Vicenta V , Uyking-Naranjo May L , Añonuevo-Cruz Ma Cecille S , Maningat Maria Patricia Deanna D , Jaring Cristina V , Nacpil-Dominguez Paulette D , Pala-Mohamad Aniza B , Canto Abigail U , Quisumbing John Paul M , Lat Annabelle Marie M , Bernardo Diane Carla C , Mansibang Noemie Marie M , Calpito Karell Jo Angelique C , Ribaya Vincent Sean D , Ferrer Julius Patrick Y , Biwang Jessica H , Melegrito Jodelyn B , Deguit Christian Deo T , Panerio Carlos Emmanuel G
Published: June 2022

Purpose

A study among Filipinos revealed that only 15% of patients with diabetes achieved glycemic control, and poor response to metformin could be one of the possible reasons. Recent studies demonstrate how genetic variations influence response to metformin. Hence, the present study aimed to determine genetic variants associated with poor response to metformin.

Methods

Using a candidate variant approach, 195 adult Filipino participants with newly diagnosed type 2 diabetes mellitus (T2DM) were enrolled in a case-control study. Genomic DNA from blood samples were collected. Allelic and genotypic associations of variants with poor response to metformin were determined using exact statistical methods.

Results

Several polymorphisms were nominally associated with poor response to metformin (Puncorr < 0.05). The most notable is the association of multiple variants in the SLC2A10 gene—rs2425911, rs3092412, and rs2425904—with common additive genetic mode of inheritance. Other variants that have possible associations with poor drug response include rs340874 (PROX-AS1), rs815815 (CALM2), rs1333049 (CDKN2B-AS1), rs2010963 (VEGFA), rs1535435 and rs9494266 (AHI1), rs11128347 (PDZRN3), rs1805081 (NPC1), and rs13266634 (SLC30A8).

Conclusion

In Filipinos, a trend for the association for several variants was noted, with further observation that several mechanisms may be involved. The results may serve as pilot data for further validation of candidate variants for T2DM pharmacotherapy.
Investigating the Effect of Estradiol Levels on the Risk of Breast, Endometrial, and Ovarian Cancer
Authors: Johansson Åsa , Schmitz Daniel , Höglund Julia , Hadizadeh Fatemeh , Karlsson Torgny , Ek Weronica E
Published: June 2022

Background

High levels of estrogen are associated with increased risk of breast and endometrial cancer and have been suggested to also play a role in the development of ovarian cancer. Cancerogenic effects of estradiol, the most prominent form of estrogen, have been highlighted as a side effect of estrogen-only menopausal hormone therapy. However, whether high levels of endogenous estrogens, produced within the body, promote cancer development, has not been fully established.

Objective

We aimed to examine causal effects of estradiol on breast, endometrial, and ovarian cancer.

Methods

Here we performed a two-sample Mendelian randomization (MR) to estimate the effect of endogenous estradiol on the risk of developing breast, endometrial, and ovarian cancer, using the UK Biobank as well as 3 independent cancer cohorts.

Results

Using 3 independent instrumental variables, we showed that higher estradiol levels significantly increase the risk for ovarian cancer (OR = 3.18 [95% CI, 1.47-6.87], P = 0.003). We also identified a nominally significant effect for ER-positive breast cancer (OR = 2.16 [95% CI, 1.09-4.26], P = 0.027). However, we could not establish a clear link to the risk of endometrial cancer (OR = 1.93 [95% CI, 0.77-4.80], P = 0.160).

Conclusion

Our results suggest that high estradiol levels promote the development of ovarian and ER-positive breast cancer.
Severe Cholestatic Jaundice (Stauffer Syndrome) as a Rare Paraneoplastic Manifestation in Adrenocortical Carcinoma
Authors: Murvelashvili Natia , Polanco Patricio M , Khorsand Sarah M , Marrero Jorge A , Jia Liwei , Mirfakhraee Sasan , Else Tobias , Habra Mouhammed Amir , Cole Suzanne , Hamidi Oksana
Published: June 2022

Background

Adrenocortical carcinoma (ACC) is a rare malignancy arising from the adrenal cortex. While ACC can be associated with adrenal hormone excess syndromes, classic paraneoplastic syndromes are rarely seen. Stauffer syndrome, a paraneoplastic phenomenon characterized by reversible cholestasis in the absence of liver metastases, has been described with renal carcinoma and other malignancies but has not been previously reported in ACC.

Case Presentation

A 38-year-old man presented with emesis, painless jaundice, pruritus, and weight loss. Laboratory evaluation demonstrated elevated total bilirubin of 8.7 mg/dL (N < 1.3 mg/dL). Computed tomography revealed a 20.4-cm left adrenal mass without evidence of liver metastases. The patient’s condition deteriorated rapidly with progressive renal failure and worsening hyperbilirubinemia. The patient underwent left adrenalectomy, nephrectomy, ureterolysis, and wedge liver biopsy. Histopathology showed necrotic ACC with tumor invasion into the adrenal capsule, no lymphovascular invasion, uninvolved margins, and Ki-67 of 40%. Kidney parenchyma exhibited diffuse pigment casts. The liver specimen contained diffuse bile deposits and minimal chronic inflammation in the portal tracts. He tested positive for the pathogenic variant of folliculin (FLCN) gene consistent with Birt-Hogg-Dube syndrome. Renal function recovered after surgery, and bilirubin level normalized after several weeks. Based on clinical presentation and absence of other etiologies, reversible cholestatic jaundice was attributed to Stauffer syndrome.

Conclusion

This is the first report of a unique presentation of paraneoplastic-related hyperbilirubinemia in the setting of ACC. While extremely rare, Stauffer syndrome should still be considered in differential diagnosis in patients with ACC with liver dysfunction and jaundice without evidence of liver metastases.
Involvement of the liver-gut peripheral neural axis in nonalcoholic fatty liver disease pathologies via hepatic HTR2A
Authors: Owaki Takashi , Kamimura Kenya , Ko Masayoshi , Nagayama Itsuo , Nagoya Takuro , Shibata Osamu , Oda Chiyumi , Morita Shinichi , Kimura Atsushi , Sato Takeki , Setsu Toru , Sakamaki Akira , Kamimura Hiroteru , Yokoo Takeshi , Terai Shuji
Published: June 2022

Serotonin (5-HT) is one of the key bioamines of nonalcoholic fatty liver disease (NAFLD). Its mechanism of action in autonomic neural signal pathways remains unexplained; hence, we evaluated the involvement of 5-HT and related signaling pathways via autonomic nerves in NAFLD. Diet-induced NAFLD animal models were developed using wild-type and melanocortin 4 receptor (MC4R) knockout (MC4RKO) mice, and the effects of the autonomic neural axis on NAFLD physiology, 5-HT and its receptors (HTRs), and lipid metabolism-related genes were assessed by applying hepatic nerve blockade. Hepatic neural blockade retarded the progression of NAFLD by reducing 5-HT in the small intestine, hepatic HTR2A and hepatic lipogenic gene expression, and treatment with an HTR2A antagonist reproduced these effects. The effects were milder in MC4RKO mice, and brain 5-HT and HTR2C expression did not correlate with peripheral neural blockade. Our study demonstrates that the autonomic liver-gut neural axis is involved in the etiology of diet-induced NAFLD and that 5-HT and HTR2A are key factors, implying that the modulation of the axis and use of HTR2A antagonists are potentially novel therapeutic strategies for NAFLD treatment.

This article has an associated First Person interview with the first author of the paper.
A Macroeconomic Perspective on Brazilian FX Swaps
Authors: Da Costa Filho Adonias Evaristo
Published: June 2022

This paper takes a macroeconomic perspective on Brazilian foreignexchange swaps. It was found that foreign exchange swap shocks lowerination, ease nancial conditions by reducing the risk premium, areassociated with temporarily higher economic activity and lower interestrates in the medium run. After a swap shock, the impact on theexchange rate is at best short-lived. A counterfactual exchange ratewithout the contribution of swap shocks shows periods when the Realwould be almost 4 percent weaker.
Trading off static efficiency and dynamic incentives in apprenticeship relations
Authors: Bitencourt Melgare Pedro
Published: June 2022

In this paper, we study a model of on-the-job training in a monopsonic environment with no enforceability and with imperfect credit markets. A market equilibrium is a relational contract which specifies a sequence of wages, a sequence of productivities for the worker and a termination date which satisfy the worker's and the firm's incentive constraint and maximize profits. We show that no self-enforceable contract can end in a period in which total surplus from employment is negative. If the surplus of employment is always positive, equilibrium contracts are perpetual and involve no wage payment before the worker is fully trained. The worker's expected productivity in an alternative employment grows exactly at the interest rate. For the particular case of a Cobb-Douglas production function for the agent, we show that training is slower for higher productivity coefficient and output elasticity. The effect of the discount rate is ambiguous.
Tail risk exposures of hedge funds: Evidence from unique Brazilian data
Authors: Almeida Caio , Fernandes Marcelo , Valente Joao Paulo
Published: June 2022

This paper examines tail risk in the Brazilian hedge fund industry. We rely on a unique data set of daily returns for every hedge fund in Brazil, dead or alive. By employing the universe of hedge funds, we ensure the absence of selection, survivorship, and instant history biases. We estimate tail risk measures based on the cross-section of both equity and hedge-fund returns. In particular, we rely on the expected shortfall of the cross-section distribution both under the physical and risk-neutral measures. We find that tail risk estimates are very different not only across asset classes (equity vs hedge fund), but also across probability measures (physical vs risk neutral). We also show that, although hedge funds in Brazil seem to exhibit more contemporaneous exposure to equity tail risk, which also partially explains the cross-section of their expected returns, hedge fund tail risk entails higher predictive ability to performance over time.
Favorable outcomes within a comprehensive therapeutic rehabilitative program in a complex case of severe polytrauma
Authors: Andone Ioana , Elisei Ioana , Daia Cristina , Popescu Cristina , Spînu Aura , Bichir Aurelia , Brumă Elena , Onose Gelu
Published: June 2022

A polytrauma patient after a car accident represents a challenge for the health care system due to the multiple traumatic injuries, at least one of them potentially being life threatening. Many of these injuries require intense nursing and rehabilitation treatment, because some of them can cause permanent disability, affecting the patient’s future quality of life. Materials and methods: With the permission of the THEBA Ethics Committee (no 24389 / 28.06.2021), this paper presents a case of a 37-year-old patient with a severe polytrauma due to a car accident (driver), occurred on October 18, 2020. The patient was hospitalized in the Intensive Care Unit of the Emergency County Hospital of Targoviste, in a severe condition, being orotracheal intubated and having a thoracic polytrauma (multiple bilateral costal fractures, anterior-superior flail chest with acute respiratory failure) and mandible fracture. After clinical and hemodynamic stabilization, he was transferred to Bucharest Emergency University Hospital and after specific paraclinical investigations, he was surgically treated with thoracic fixation with metal plates, sternal fixation with plate and screws, thoraco-abdominal skin grafting and mandibular stabilization. Afterwards he was transferred to THEBA at the Plastic Surgery Clinic Department for lumbar-sacral pressure sore, where he suffered multiple surgical interventions. In our Neuromuscular Rehabilitation Department, the patient was admitted in 16.02.2021 with pain and severe functional impairments in the right elbow and the right knee, surgically treated sacral pressure sore still in the process of healing and having a severe deficiency of self-care and locomotion. He initially followed a rehabilitative nursing program and continued with a recovery therapy according to clinical stages. The patient was functionally assessed using the following scales: Medical Research Council (MRC) Scale for Muscle Strength, Functional Independence Measure (FIM), Life Quality Assessment (QOL), FAC International Scale and Independence Assessment Scale in Daily Activities (ADL/IADL). Results: Although the patient's evolution was slow, he had favorable outcomes with an increase in the scores of the evaluated scales at discharge. He benefited from specific surgical care of the pressure sores and a complex neuro-muscular rehabilitative program. The patient’s final performance in our clinic was walking on medium distances with support from another person. Conclusion: The multidisciplinary team approach with the addition of complex nursing measures and a personalized rehabilitative program for a young patient with polytrauma caused by a car accident established neuro-locomotor improvements which led to an increase in patient’s quality of life.
Keywords: neuro-muscular rehabilitation, polytrauma
Kinesiotherapy and physical activity in COPD and Asthma
Patients – A Review
Authors: Teoibas-Serban Doroteea , Blendea Corneliu-Dan , Mihaltan Florin
Published: June 2022

Background: Obstructive chronic diseases are a continuous challenge for healthcare perfusionists all over the world. Asthma and Chronic Obstructive Pulmonary Disease (COPD) are the most frequent of these diseases. Respiratory or pulmonary rehabilitation started to gain momentum and it is more frequently used to improve muscle strength, cardiac and respiratory endurance and joint flexibility. The objective of this paper is to establish the current programs of physical activity or kinesiotherapy used in the past year and to reveal if there are any gaps or mismatches in the development of the program or in the instruments used to quantify the results of the rehabilitation programs. Materials and methods: We reviewed a total number of 12 articles, randomized control trials using the search words kinesiotherapy, physical therapy, COPD and asthma from the last year on PubMed.gov, from 11 different countries in order to establish which have similar types of exercises, parameters used in order to compare results and which were the outcomes. Results: The final results are positive, although it is hard to determine a unity because there were so many different parameters used to monitor the patients. The most frequent parameter was the 6MWT used to compare the effectiveness of the physical program in 6 studies. Discussion and conclusions: This review had its limitation in comparing the 12 articles researched because of the different number of patients, the various physical activity and rehabilitation exercises used, but especially because of the many varieties of scales and scores used to monitor the effectiveness of the treatment. In order to successfully compare such papers, an international guideline is necessary to relay specific rehabilitation programs for every type of respiratory pathology and also which are the most recommended scales or scores or parameters in general to asses such rehabilitation programs.
Keywords: kinesiotherapy; physical activity; physical therapy; COPD, asthma
Ο τόπος παροχής
Authors: Καράμπελα Ναταλία
Published: June 2022

Ο τόπος είναι στοιχείο της παροχής και προσδιορίζει γεωγραφικά τον τόπο συμπεριφοράς του οφειλέτη. Συνιστά τον τόπο στον οποίο υποχρεούται σε εκπλήρωση ο οφειλέτης και αντίστοιχα ο δανειστής να αποδεχθεί. Εντάσσεται συστηματικά στο Γενικό Ενοχικό Δίκαιο και αφορά την φυσιολογία της ενοχής, ενώ σχετίζεται με την ομαλή εξέλιξη της ενοχής και την απόσβεση. Σκοπός της παρούσας εργασίας είναι να αναδειχθεί το ερμηνευτικό περιεχόμενο του τόπου παροχής, η έννοια του τόπου και πώς προσαρμόζεται στην σύγχρονη συναλλακτική πρακτική δεδομένου, ότι οι ρυθμίσεις του Αστικού Κώδικα για τον τόπο παροχής αντανακλούν το πλαίσιο μίας παραδοσιακής οικονομίας. Εξετάζεται συνεπώς κατά πόσον η έννοια του τόπου της παροχής προσδιορίζεται, διαμορφώνεται και προσαρμόζεται ανάλογα με την εκάστοτε έννομη σχέση και την φύση των συναλλαγών ως παραδοσιακών ή σύγχρονων.Η εργασία χωρίζεται σε εννέα κεφάλαια, εκκινώντας από το ρυθμιστικό πλαίσιο για τον τόπο παροχής, την ιστορική και συγκριτική επισκόπηση. Ακολουθεί ο αρχικός προσδιορισμός του τόπου παροχής ανάλογα με την φύση του χρέους ως χρηματικού και μη και ο προσδιορισμός του τόπου των συνεχόμενων με την κύρια λοιπών παροχών. Περαιτέρω, εξετάζεται ο προσδιορισμός του τόπου στο δίκαιο της πώλησης, οι επερχόμενες έννομες συνέπειες και η αναφορά του τόπου παροχής ως βάσεως δωσιδικίας. Τέλος, επιχειρείται ο προσδιορισμός του τόπου της παροχής σε ατοπικό περιβάλλον, όπως το διαδίκτυο.
Modern approaches to revealing hidden information
Authors: Aref'eva Oksana
Published: June 2022

the article is devoted to an urgent problem - the identification of hidden information. Many scientific studies of domestic and foreign authors reveal this topic in order to provide practical assistance in the framework of crime detection and personnel selection of candidates for service. However, research in this area is still ongoing, since a universal method has not yet been found that takes into account all kinds of informative sources of information received. The topic of detecting lies in statements during investigative activities, personnel selection of candidates for service remains not fully disclosed and requires further research. The article analyzes the existing modern methods of lie recognition, both instrumental and without the use of special equipment, and compares the reliability of the information received. Based on the study and generalization of existing modern methods, the author comes to the conclusion that combined methods of diagnosing false information are most effective when the equipment is auxiliary, complementing the main method and serves to fix the processes taking place