bluuebunny/crossref_metadata_2025 huggingface dataset:
Primary colonic melanoma: a rare entity
Authors: Xie Junhua , Dai Gang , Wu Yuhao
Published: August 2022

Gastrointestinal melanoma is usually metastatic in origin, and primary melanoma within the gastrointestinal tract is rarely reported. Colon is considered to be an extremely uncommon site for primary melanomas. Herein, we report the first case of a large primary melanoma within the transverse colon with gastric involvement. CT scan found a mass within the colon, which seemed to connect to the gastric antrum. Esophagogastroscopy showed an ulcerated lesion in the greater curvature of the stomach. Subsequent colonoscopy identified a large ulcerated lesion rendering significant stenosis of the transverse colon. Biopsy following colonoscopy indicated a diagnosis of colonic melanoma based on pathological findings, which identified submucosal malignant melanoma cells with epithelioid and spindle features. Immunohistochemical stains were positive for S-100, HMB-45, Vimentin, and Melan-A. A series of clinical and imaging examinations revealed no suspicious primary cutaneous or ocular lesions. The diagnosis of primary colonic melanoma was considered. A radical transverse colectomy with subtotal gastrectomy were conducted subsequently. Definite diagnosis of primary colonic melanoma can be established after ruling out the possibility of being a metastasis from other more common primary sites. Primary colonic melanomas are a challenge to diagnose and often need a multidisciplinary treatment approach, including surgery, BRAF-targeted therapy, and immunotherapy.
The role of macrophages phenotypes in the activation of resolution pathways within human granulosa cells
Authors: Martins Thaise S. , Fonseca Bruno M. , Rebelo Irene
Published: August 2022

Background

Inflammatory state within the ovaries can disrupt normal follicular dynamics, leading to reduced oocyte quality and infertility. How the production of inflammatory mediators generated by macrophages with different gene expression profile (M1 and M2) might activate inflammatory pathways, such as cyclooxygenase-2 (COX-2) and 5-, 12-, and 15-lipoxygenase (LOX), in human granulosa cells (hGCs) remains unclear.

Methods

In this study, we evaluated how M1 and M2 macrophages found in the ovaries affect the functions of hGCs isolated from women undergoing assisted reproductive technology (ART) and human ovarian granulosa COV434 cells. For this purpose, a model of interaction between hGCs and COV434 cells and conditioned media (CMs) obtained from culture of M0, M1 and M2 macrophages was established. We used real-time PCR and western blotting to detect the expression of COX-2 and 5-, 12-, and 15-LOX as biomarkers of oocyte competence.

Results

Our data showed that M2 macrophages with anti-inflammatory characteristics were able to significantly increase the expression of COX-2 in hGCs. We also demonstrated that M1 macrophages with pro-inflammatory characteristics were able to significantly increase the expression of 12-LOX in hGCs. However, there was no observed expression of 5-LOX and no significant alteration in the expression of 15-LOX in hGCs. Regarding COV434 cells, we found that CM from M2 macrophage resulted in an increase in COX-2, 5-LOX and 15-LOX mRNA and protein levels. No expression of 12-LOX by COV434 cells was observed when exposed to CMs from M1 and M2 macrophages.

Conclusions

Our research indicated that the production of pro-resolving mediators by hGCs can, at least in part, reverse the physiological inflammation present in the ovaries.
Androgen receptor variant-7 regulation by tenascin-c induced src activation
Authors: Thomas Rintu , Jerome John Michael , Dang Truong D. , Souto Eric P. , Mallam Joshua N. , Rowley David R.
Published: August 2022

Background

Bone metastatic prostate cancer does not completely respond to androgen-targeted therapy and generally evolves into lethal castration resistant prostate cancer (CRPC). Expression of AR-V7- a constitutively active, ligand independent splice variant of AR is one of the critical resistant mechanisms regulating metastatic CRPC. TNC is an extracellular matrix glycoprotein, crucial for prostate cancer progression, and associated with prostate cancer bone metastases. In this study, we investigated the mechanisms that regulate AR-V7 expression in prostate cancer cells interacting with osteogenic microenvironment including TNC.

Methods

Prostate cancer/preosteoblast heterotypical organoids were evaluated via immunofluorescence imaging and gene expression analysis using RT-qPCR to assess cellular compartmentalization, TNC localization, and to investigate regulation of AR-V7 in prostate cancer cells by preosteoblasts and hormone or antiandrogen action. Prostate cancer cells cultured on TNC were assessed using RT-qPCR, Western blotting, cycloheximide chase assay, and immunofluorescence imaging to evaluate (1) regulation of AR-V7, and (2) signaling pathways activated by TNC. Identified signaling pathway induced by TNC was targeted using siRNA and a small molecular inhibitor to investigate the role of TNC-induced signaling activation in regulation of AR-V7. Both AR-V7- and TNC-induced signaling effectors were targeted using siRNA, and TNC expression assessed to evaluate potential feedback regulation.

Results

Utilizing heterotypical organoids, we show that TNC is an integral component of prostate cancer interaction with preosteoblasts. Interaction with preosteoblasts upregulated both TNC and AR-V7 expression in prostate cancer cells which was suppressed by testosterone but elevated by antiandrogen enzalutamide. Interestingly, the results demonstrate that TNC-induced Src activation regulated AR-V7 expression, post-translational stability, and nuclear localization in prostate cancer cells. Treatment with TNC neutralizing antibody, Src knockdown, and inhibition of Src kinase activity repressed AR-V7 transcript and protein. Reciprocally, both activated Src and AR-V7 were observed to upregulate autocrine TNC gene expression in prostate cancer cells.

Conclusion

Overall, the findings reveal that prostate cancer cell interactions with the cellular and ECM components in the osteogenic microenvironment plays critical role in regulating AR-V7 associated with metastatic CRPC.
CRISPR/Cas9 genome editing to create nonhuman primate models for studying stem cell therapies for HIV infection
Authors: Schmidt Jenna Kropp , Reynolds Matthew R. , Golos Thaddeus G. , Slukvin Igor I.
Published: August 2022

Nonhuman primates (NHPs) are well-established basic and translational research models for human immunodeficiency virus (HIV) infections and pathophysiology, hematopoietic stem cell (HSC) transplantation, and assisted reproductive technologies. Recent advances in CRISPR/Cas9 gene editing technologies present opportunities to refine NHP HIV models for investigating genetic factors that affect HIV replication and designing cellular therapies that exploit genetic barriers to HIV infections, including engineering mutations into CCR5 and conferring resistance to HIV/simian immunodeficiency virus (SIV) infections. In this report, we provide an overview of recent advances and challenges in gene editing NHP embryos and discuss the value of genetically engineered animal models for developing novel stem cell-based therapies for curing HIV.
Upper limb soft robotic wearable devices: a systematic review
Authors: Bardi Elena , Gandolla Marta , Braghin Francesco , Resta Ferruccio , Pedrocchi Alessandra L. G. , Ambrosini Emilia
Published: August 2022

Introduction

Soft robotic wearable devices, referred to as exosuits, can be a valid alternative to rigid exoskeletons when it comes to daily upper limb support. Indeed, their inherent flexibility improves comfort, usability, and portability while not constraining the user’s natural degrees of freedom. This review is meant to guide the reader in understanding the current approaches across all design and production steps that might be exploited when developing an upper limb robotic exosuit.

Methods

The literature research regarding such devices was conducted in PubMed, Scopus, and Web of Science. The investigated features are the intended scenario, type of actuation, supported degrees of freedom, low-level control, high-level control with a focus on intention detection, technology readiness level, and type of experiments conducted to evaluate the device.

Results

A total of 105 articles were collected, describing 69 different devices. Devices were grouped according to their actuation type. More than 80% of devices are meant either for rehabilitation, assistance, or both. The most exploited actuation types are pneumatic (52%) and DC motors with cable transmission (29%). Most devices actuate 1 (56%) or 2 (28%) degrees of freedom, and the most targeted joints are the elbow and the shoulder. Intention detection strategies are implemented in 33% of the suits and include the use of switches and buttons, IMUs, stretch and bending sensors, EMG and EEG measurements. Most devices (75%) score a technology readiness level of 4 or 5.

Conclusion

Although few devices can be considered ready to reach the market, exosuits show very high potential for the assistance of daily activities. Clinical trials exploiting shared evaluation metrics are needed to assess the effectiveness of upper limb exosuits on target users.
No travel worsens depression: reciprocal relationship between travel and depression among older adults
Authors: Hyun Seungjae , Lee Yeonjin , Park Sangshin
Published: August 2022

Background

The aim of this study was to examine the bidirectional relationship between depression and travel.

Method

We analyzed 8524 participants’ data obtained from the 2008 to 2016 waves of the Korean Longitudinal Study of Ageing, a prospective cohort study. Depression was diagnosed using the Center for Epidemiological Studies Depression Scale: 10-Items (CES-D10), with scores of 4 or higher indicating depression. We used a generalized estimating equation and a cross-lagged panel model for statistical analysis.

Results

Participants who had not traveled for one year had a 71% higher risk of suffering from depression in the following year than did those who had traveled [relative risk (RR) = 1.71, P < 0.001], and participants with depression had more than double the increased risk of not traveling than did those not currently suffering from depression (RR = 2.08, P < 0.001). The cross-lagged panel model confirmed the vicious cycle involving the amount of travel and score on the CES-D10; individuals who traveled more frequently were more likely to have lower scores on the CES-D10 (coefficient = − 0.04 to − 0.03, Ps < 0.01), and individuals with higher scores were less likely to travel (coefficient = − 0.06 to − 0.03, Ps < 0.01).

Conclusions

The risk of depression increases for people who do not travel, and a reciprocal relationship exists between travel and depression.
Aboriginal medicinal plants of Queensland: ethnopharmacological uses, species diversity, and biodiscovery pathways
Authors: Turpin Gerry , Ritmejerytė Edita , Jamie Joanne , Crayn Darren , Wangchuk Phurpa
Published: August 2022

Background

Aboriginal peoples have occupied the island continent of Australia for millennia. Over 500 different clan groups or nations with distinctive cultures, beliefs, and languages have learnt to live sustainably and harmoniously with nature. They have developed an intimate and profound relationship with the environment, and their use of native plants in food and medicine is largely determined by the environment they lived in. Over 1511 plant species have been recorded as having been used medicinally in Australia. Most of these medicinal plants were recorded from the Aboriginal communities in Northern Territory, New South Wales, South Australia, and Western Australia. Not much has yet been reported on Aboriginal medicinal plants of Queensland. Therefore, the main aim of this review is to collect the literature on the medicinal plants used by Aboriginal peoples of Queensland and critically assess their ethnopharmacological uses.

Methods

The information used in this review was collected from archival material and uploaded into the Tropical Indigenous Ethnobotany Centre (TIEC) database. Archival material included botanist’s journals/books and old hard copy books. Scientific names of the medicinal plant species were matched against the ‘World Flora Online Plant List’, and ‘Australian Plant Census’ for currently accepted species names to avoid repetition. An oral traditional medical knowledge obtained through interviewing traditional knowledge holders (entered in the TIEC database) has not been captured in this review to protect their knowledge.

Results

This review identified 135 species of Queensland Aboriginal medicinal plants, which belong to 103 genera from 53 families, with Myrtaceae being the highest represented plant family. While trees represented the biggest habit, leaves were the most commonly used plant parts. Of 62 different diseases treated by the medicinal plants, highest number of plants are used for treating skin sores and infections. Few plants identified through this review can be found in other tropical countries but many of these medicinal plants are native to Australia. Many of these medicinal plants are also used as bush food by Aboriginal peoples.

Conclusion

Through extensive literature review, we found that 135 medicinal plants native to Queensland are used for treating 62 different diseases, especially skin infections. Since these medicinal plants are also used as bush food and are rarely studied using the Western scientific protocols, there is a huge potential for bioprospecting and bush food industry.
CDK7 inhibition augments response to multidrug chemotherapy in pancreatic cancer
Authors: Zeng Siyuan , Lan Bin , Ren Xiaofan , Zhang Shuman , Schreyer Daniel , Eckstein Markus , Yang Hai , Britzen-Laurent Nathalie , Dahl Andreas , Mukhopadhyay Debabrata , Chang David , Kutschick Isabella , Pfeffer Susanne , Bailey Peter , Biankin Andrew , Grützmann Robert , Pilarsky Christian
Published: August 2022

Background

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with a dismal prognosis. Although combined treatment with gemcitabine and albumin-bound paclitaxel has improved the prognosis of PDAC, both intrinsic and acquired chemoresistance remain as severe hurtles towards improved prognosis. Thus, new therapeutic targets and innovative strategies are urgently needed.

Methods

In this study, we used the KPC mouse model-derived PDAC cell line TB32047 to perform kinome-wide CRISPR-Cas9 loss-of-function screening. Next-generation sequencing and MAGeCK-VISPR analysis were performed to identify candidate genes. We then conducted cell viability, clonogenic, and apoptosis assays and evaluated the synergistic therapeutic effects of cyclin-dependent kinase 7 (CDK7) depletion or inhibition with gemcitabine (GEM) and paclitaxel (PTX) in a murine orthotopic pancreatic cancer model. For mechanistic studies, we performed genome enrichment analysis (GSEA) and Western blotting to identify and verify the pathways that render PDAC sensitive to GEM/PTX therapy.

Results

We identified several cell cycle checkpoint kinases and DNA damage-related kinases as targets for overcoming chemoresistance. Among them, CDK7 ranked highly in both screenings. We demonstrated that both gene knockout and pharmacological inhibition of CDK7 by THZ1 result in cell cycle arrest, apoptosis induction, and DNA damage at least predominantly through the STAT3-MCL1-CHK1 axis. Furthermore, THZ1 synergized with GEM and PTX in vitro and in vivo, resulting in enhanced antitumor effects.

Conclusions

Our findings support the application of CRISPR-Cas9 screening in identifying novel therapeutic targets and suggest new strategies for overcoming chemoresistance in pancreatic cancer.
Flow cytometry-based viability staining: an at-line tool for bioprocess monitoring of Sulfolobus acidocaldarius
Authors: Rastädter Kerstin , Tramontano Andrea , Wurm David J. , Spadiut Oliver , Quehenberger Julian
Published: August 2022

Determination of the viability, ratio of dead and live cell populations, of Sulfolobus acidocaldarius is still being done by tedious and material-intensive plating assays that can only provide time-lagged results. Although S. acidocaldarius, an extremophilic Archaeon thriving at 75 °C and pH 3.0, and related species harbor great potential for the exploitation as production hosts and biocatalysts in biotechnological applications, no industrial processes have been established yet. One hindrance is that during development and scaling of industrial bioprocesses timely monitoring of the impact of process parameters on the cultivated organism is crucial—a task that cannot be fulfilled by traditional plating assays. As alternative, flow cytometry (FCM) promises a fast and reliable method for viability assessment via the use of fluorescent dyes. In this study, commercially available fluorescent dyes applicable in S. acidocaldarius were identified. The dyes, fluorescein diacetate and concanavalin A conjugated with rhodamine, were discovered to be suitable for viability determination via FCM. For showing the applicability of the developed at-line tool for bioprocess monitoring, a chemostat cultivation on a defined growth medium at 75 °C, pH 3.0 was conducted. Over the timeframe of 800 h, this developed FCM method was compared to the plating assay by monitoring the change in viability upon controlled pH shifts. Both methods detected an impact on the viability at pH values of 2.0 and 1.5 when compared to pH 3.0. A logarithmic relationship between the viability observed via plating assay and via FCM was observed.
Changes of the liver metabolome following an intravenous lipopolysaccharide injection in Holstein cows supplemented with dietary carnitine
Authors: Xu Wei , Grindler Sandra , Kenéz Ákos , Dänicke Sven , Frahm Jana , Huber Korinna
Published: August 2022

Background

Carnitine facilitates the flux of long-chain fatty acids for hepatic mitochondrial beta-oxidation, which acts to ameliorate the negative energy balance commonly affecting high-yielding dairy cows. Inflammation triggered by lipopolysaccharide (LPS) load can however pose a challenge to the metabolic integrity via the expression of pro-inflammatory mediators, leading to immune system activation and respective metabolic alterations. The effect of enhanced carnitine availability on hepatic metabolome profiles during an inflammatory challenge has not yet been determined in dairy cows. Herein, Holstein cows were supplemented with 25 g/d rumen-protected carnitine from 42 d prepartum until 126 d postpartum (n = 16) or assigned to the control group with no supplementation during the same period (n = 14). We biopsied the liver of the cows before (100 d postpartum) and after (112 d postpartum) an intravenous injection of 0.5 µg/kg LPS. Liver samples were subjected to a targeted metabolomics analysis using the AbsoluteIDQ p180 Kit (Biocrates Life Sciences AG, Innsbruck, Austria). 

Results

Multivariate statistical analyses revealed that hepatic metabolome profiles changed in relation to both the carnitine supplementation and the LPS challenge. Comparing the metabolite profiles on 100 d, carnitine increased the concentration of short- and long-chain acyl-carnitines, which may be explained by an enhanced mitochondrial fatty acid shuttle and hence greater energy availability. The LPS injection affected hepatic metabolite profiles only in the carnitine supplemented group, particularly altering the concentration of biogenic amines.

Conclusions

Our results point to interactions between an acute hepatic inflammatory response and biogenic amine metabolism, depending on energy availability.
Wearable reproductive trackers: quantifying a key life history event remotely
Authors: Ozsanlav-Harris Luke , Griffin Larry R. , Weegman Mitch D. , Cao Lei , Hilton Geoff M. , Bearhop Stuart
Published: August 2022

Advancements in biologging technology allow terabytes of data to be collected that record the location of individuals but also their direction, speed and acceleration. These multi-stream data sets allow researchers to infer movement and behavioural patterns at high spatiotemporal resolutions and in turn quantify fine-scale changes in state along with likely ecological causes and consequences. The scope offered by such data sets is increasing and there is potential to gain unique insights into a suite of ecological and life history phenomena. We use multi-stream data from global positioning system (GPS) and accelerometer (ACC) devices to quantify breeding events remotely in an Arctic breeding goose. From a training set of known breeders we determine the movement and overall dynamic body acceleration patterns indicative of incubation and use these to classify breeding events in individuals with unknown reproductive status. Given that researchers are often constrained by the amount of biologging data they can collect due to device weights, we carry out a sensitivity analysis. Here we explore the relative merits of GPS vs ACC data and how varying the temporal resolution of the data affects the accuracy of classifying incubation for birds. Classifier accuracy deteriorates as the temporal resolution of GPS and ACC are reduced but the reduction in precision (false positive rate) is larger in comparison to recall (false negative rate). Precision fell to 94.5%, whereas recall didn’t fall below 98% over all sampling schedules tested. Our data set could have been reduced by c.95% while maintaining precision and recall > 98%. The GPS-only classifier generally outperformed the ACC-only classifier across all accuracy metrics but both performed worse than the combined GPS and ACC classifier. GPS and ACC data can be used to reconstruct breeding events remotely, allowing unbiased, 24-h monitoring of individuals. Our resampling-based sensitivity analysis of classifier accuracy has important implications with regards to both device design and sampling schedules for study systems, where device size is constrained. It will allow researchers with similar aims to optimize device battery, memory usage and lifespan to maximise the ability to correctly quantify life history events.
Pharmacovigilance of cutaneous adverse drug reactions in associations with drugs and medical conditions: a retrospective study of hospitalized patients
Authors: Zheng Lei , Jin Hao-bin , Guan Yu-yao , Yang Jing
Published: August 2022

Background

Cutaneous adverse drug reaction (CADR) is a common problem in clinical medication. This study aimed to investigate the correlation between clinical drug application and CADR occurrence as evidence for preventive strategies and rational clinical drug use.

Methods

We analyzed the characteristics of CADRs of 858 patients admitted to Shandong Provincial Third Hospital from March 2007 to December 2018. The most significant drugs concerning the common skin symptoms and their significance to CADR were investigated by case-non-case and multiple logistic regression analyses.

Results

A total of 266 drugs were involved in 858 cases of CADR. Among the ten most relevant medications, primarily antibiotics and herbal injections, and nutritional support drugs, potassium sodium dehydroandrographolide succinate injection, and cefoperazone sodium and sulbactam sodium injection were found to be 2.1 and 1.45 times statistically more prone to CADRs than to other adverse drug reactions (ADRs), respectively. The main route of administration was intravenous (63.16%), with oral administration accounting for 25.19%. There were 747 cases of ADR, 71 of severe ADR, 2 of new and severe ADRs, and 38 cases of new ADR. Overall, 100 cases of CADR exhibited abnormal alanine aminotransferase, aspartate aminotransferase, and serum creatinine levels. The predictive factors for severe CADR occurrence included allergy and smoking histories, cefoperazone sodium, sulbactam sodium injection, levofloxacin lactate and sodium chloride injection.

Conclusions

Drug-induced CADR symptoms are commonly associated with other ARDs, predominantly rashes and pruritus, and are often accompanied by some medical conditions, especially liver and kidney damage. Detailed attention to a patient’s primary diseases, allergy history, and drug safety profile could help prevent or reverse CADR in most patients.
HIV, tuberculosis, diabetes mellitus and hypertension admissions and premature mortality among adults in Uganda from 2011 to 2019: is the tide turning?
Authors: Kazibwe Andrew , Bisaso Kuteesa Ronald , Kyazze Andrew Peter , Ninsiima Sandra , Ssekamatte Phillip , Bongomin Felix , Baluku Joseph Baruch , Kibirige Davis , Akabwai George Patrick , Kamya Moses R. , Mayanja-Kizza Harriet , Byakika-Kibwika Pauline , Kagimu Magid , Kalyesubula Robert , Andia-Biraro Irene
Published: August 2022

Background

The growing burden of diabetes mellitus (DM) and hypertension (HTN) on the background of endemic Human Immuno-deficiency Virus (HIV) and tuberculosis (TB) is a concern in low- and middle-income countries. We aimed to describe annual trends in admissions, mortality rates and premature mortality (years of potential life lost—YPLLs) due to HIV, tuberculosis (TB), diabetes mellitus (DM) and hypertension (HTN) in Uganda.

Methods

We conducted a retrospective cohort study, retrieving electronic records of adults admitted to Mulago and Kiruddu national referral hospitals medical wards between 1st January 2011 and 31st December 2019. We used STATA BE 17.0 and GraphPad Prism 8.0.2 to compute total admissions, inpatient crude mortality rates, and YPLLs; and demonstrate trends using Mann–Kendall test.

Results

Of 108,357 admissions, 55,620 (51.3%) were female, 15,300 (14.1%) were recorded in 2012, and 22,997 (21.2%) were aged 21–30 years. HIV, TB, DM and HTN accounted for 26,021 (24.0%); 9537 (8.8%); 13,708 (12.7) and 13,252 (12.2%) of all admissions, respectively. Overall inpatient mortality was 16.7% (18,099/108,357), 53.5% (9674/18,099) were male, 21.5% (3898) were aged 31–40 years and 2597 (14.4%) were registered in 2013. HIV, TB, DM and HTN accounted for 35.6% (6444), 14.6% (2646), 9.1% (1648) and 11.8% (2142) of all deaths, respectively. Total admissions (Kendall’s tau-B = − 0.833, p < 0.001) and deaths declined (Kendall’s tau-B = − 0.611, p = 0.029). A total of 355,514 (mean = 20.8 years, SD 30.0) YPLLs were recorded, of which 54.6% (191,869) were in males; 36.2% (128,755) were among those aged 21–30 years and were recorded in 2012 (54,717; 15.4%). HIV, TB, DM and HTN accounted for 46.5% (165,352); 19.5% (69,347); 4.8% (16,991) and 4.5% (16,167) of YPLLs, respectively. Proportionate contribution of HIV to deaths and YPLLs declined, remained stagnant for TB; and increased for both DM and HTN.

Conclusion

TB and HIV account for higher though declining, while DM and HTN account for lower albeit rising morbidity and premature mortality among adult medical patients in Uganda. TB prevention and treatment; and DM/HTN service integration in HIV care should be optimized and scaled up.
Identification of some native entomopathogenic fungal species and their pathogenicity against Apple Blossom Beetle, Tropinota (Epicometis) hirta (Poda, 1761) (Coleoptera: Cetoniidae) adults
Authors: Uçar Seher , Atay Turgut , Yanar Yusuf
Published: August 2022

Background

Entomopathogenic fungi (EPFs) have more important role in biological control of the important insect pests. In the present study 15 EPF isolates, selected from the EPF culture collection, were identified using molecular methods and their effectiveness against adults of Apple Blossom Beetle (ABB) [Tropinota (= Epicometis) hirta (Poda, 1761) (Coleoptera: Cetoniidae)] was investigated. To determine virulence of isolates against ABB adults, primarily a single-concentration trial was conducted at 1 × 107 conidia ml−1. Furthermore, concentration-mortality trials were conducted with some isolates that were determined to have a high effect, employing concentrations of 1 × 106, 1 × 108, and 1 × 109 conidia ml−1. For isolates tested in concentration-mortality trials, LT30, LT50 and LT90 values at a concentration of 1 × 108 conidia ml−1 were calculated using probit analysis.

Results

Molecular diagnostic tests revealed that the 13 isolates were Beauveria bassiana, 1 isolate was Clonostachys rosea, and 1 isolate was Purpureocillium lilacinum. According to the single- concentration trial data, some isolates with high efficacy were selected (GN16, GN22-1, GN29-1, HP3-1 and HP33-1) and concentration-mortality trials were established with these isolates using 1 × 106, 1 × 108 and 1 × 109 conidia ml−1 concentrations. According to the results of the concentration-mortality trials, all isolates used in 1 × 108 and 1 × 109 conidia ml−1 concentrations started to show a significant effect from the 11th day, and at the end of the 17th day, the effect in all concentrations was over 90% (except 1 × 106 conidia ml−1 concentration of GN22-1).

Conclusions

According to the data obtained, all isolates used in concentration-mortality trials were effective against ABB adults. With these isolates, more detailed studies should be conducted under orchard conditions.
Comparison of psychiatric disorders in addicted patients treated with buprenorphine, methadone, and opium tincture in Iran
Authors: Bahadori Zahra , Safaie Nilufar , Mirmohammadkhani Majid
Published: August 2022

Background

The aim of this study was to comparing the complications (depression, anxiety, sleep disorders and sexual dysfunction) of buprenorphine, methadone and opium tincture as an alternative drug treatment in patients referred to the National Center for Addiction Studies of Tehran during 2020–2021. This cross-sectional study was concocted on 197 patients referred to the National Center for Addiction Studies of Tehran who were treated with one of the alternative treatments of opioids buprenorphine (n = 24), methadone (n = 116), and opium tincture (n = 57) during 2020–2021. Three questionnaires were used to assess the side effects of drugs including Anxiety and Depression Hospital Scales (HADS), AIS (Athens insomnia scale) and the International Index of Erectile Function (IIEF). Data were analyzed using Stata 14.0. The multinomial logistic regression model was used in order to compare complications in the three groups and adjusted odds ratio (OR) with 95% confidence interval (CI) were estimated.

Results

The mean age in the buprenorphine, methadone and opium tincture groups were 46.80 ± 9.90, 48.31 ± 13.33 and 55.30 ± 10.34 years, respectively. The numbers of men were 17 (70.80), 90 (77.60), and 50 (78.70); respectively. Multinomial logistic regression model showed OR = 0.73 (95% CI 0.61–0.88) for anxiety in the methadone group in compared to buprenorphine. Likewise, OR = 1.22 (95% CI 1.001–1.48) and OR = 1.34 (95% CI 1.10–1.63) was observed for sleep disorder in the methadone and opium tincture groups in compared to buprenorphine; respectively.

Conclusions

Sleep disturbance in buprenorphine group is less than opium tincture and methadone. Also, anxiety in the methadone group was lower than the buprenorphine, however, there was no significant difference between the three groups in term of sexual function and depression. In addition to control measures for sleep disorders in receiving methadone and buprenorphine, the cohort studies with a higher sample size are recommended.
Ripretinib Versus Sunitinib in Patients With Advanced Gastrointestinal Stromal Tumor After Treatment With Imatinib (INTRIGUE): A Randomized, Open-Label, Phase III Trial
Authors: Bauer Sebastian , Jones Robin L. , Blay Jean-Yves , Gelderblom Hans , George Suzanne , Schöffski Patrick , von Mehren Margaret , Zalcberg John R. , Kang Yoon-Koo , Razak Albiruni Abdul , Trent Jonathan , Attia Steven , Le Cesne Axel , Su Ying , Meade Julie , Wang Tao , Sherman Matthew L. , Ruiz-Soto Rodrigo , Heinrich Michael C.
Published: August 2022

PURPOSE

Sunitinib, a multitargeted tyrosine kinase inhibitor (TKI), is approved for advanced gastrointestinal stromal tumor (GIST) after imatinib failure. Ripretinib is a switch-control TKI approved for advanced GIST after prior treatment with three or more TKIs, including imatinib. We compared efficacy and safety of ripretinib versus sunitinib in patients with advanced GIST who were previously treated with imatinib (INTRIGUE, ClinicalTrials.gov identifier: NCT03673501 ).

PATIENTS AND METHODS

Random assignment was 1:1 to once-daily ripretinib 150 mg or once-daily sunitinib 50 mg (4 weeks on/2 weeks off) and stratified by KIT/ platelet-derived growth factor α mutation and imatinib intolerance. The primary end point was progression-free survival (PFS) by independent radiologic review using modified Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end points included objective response rate by independent radiologic review, safety, and patient-reported outcome measures.

RESULTS

Overall, 453 patients were randomly assigned to ripretinib (intention-to-treat [ITT], n = 226; KIT exon 11 ITT, n = 163) or sunitinib (ITT, n = 227; KIT exon 11 ITT, n = 164). Median PFS for ripretinib and sunitinib ( KIT exon 11 ITT) was 8.3 and 7.0 months, respectively (hazard ratio, 0.88; 95% CI, 0.66 to 1.16; P = .36); median PFS (ITT) was 8.0 and 8.3 months, respectively (hazard ratio, 1.05; 95% CI, 0.82 to 1.33; nominal P = .72). Neither was statistically significant. Objective response rate was higher for ripretinib versus sunitinib in the KIT exon 11 ITT population (23.9% v 14.6%, nominal P = .03). Ripretinib was associated with a more favorable safety profile, fewer grade 3/4 treatment-emergent adverse events (41.3% v 65.6%, nominal P < .0001), and better scores on patient-reported outcome measures of tolerability.

CONCLUSION

Ripretinib was not superior to sunitinib in terms of PFS. However, meaningful clinical activity, fewer grade 3/4 treatment-emergent adverse events, and improved tolerability were observed with ripretinib.
Elusive anomalies
Authors: Bonora L.
Published: August 2022

Usually, in order to compute an anomaly (be it chiral or trace) with a perturbative method, the lowest significant order is sufficient. With the help of gauge or diffeomorphism invariance it uniquely identifies the anomaly. This note is a short review of the ambiguities that arise in the calculation of trace anomalies, and is meant, in particular, to signal cases in which the lowest perturbative order is not enough to unambiguously identify a trace anomaly. This may shed light on some recent contradictory results.
Prevalence of Subclinical Papillary Thyroid Cancer by Age: Meta-analysis of Autopsy Studies
Authors: Arroyo Natalia , Bell Katy J L , Hsiao Vivian , Fernandes-Taylor Sara , Alagoz Oguzhan , Zhang Yichi , Davies Louise , Francis David O
Published: August 2022

Context

It is not known how underlying subclinical papillary thyroid cancer (PTC) differs by age. This meta-analysis of autopsy studies investigates how subclinical PTC prevalence changes over the lifetime.

Methods

We searched PubMed, Embase, and Web of Science databases from inception to May 2021 for studies that reported the prevalence of PTC found at autopsy. Two investigators extracted the number of subclinical PTCs detected in selected age groups and extent of examination. A quality assessment tool was used to assess bias. Logistic regression models with random intercepts were used to pool the age-specific subclinical PTC prevalence estimates.

Results

Of 1773 studies screened, 16 studies with age-specific data met the inclusion criteria (n = 6286 autopsies). The pooled subclinical PTC prevalence was 12.9% (95% CI 7.8-16.8) in whole gland and 4.6% (2.5- 6.6) in partial gland examination. Age-specific prevalence estimates were ≤40 years, 11.5% (6.8-16.1); 41-60 years, 12.1% (7.6-16.5); 61-80 years, 12.7% (8-17.5); and 81+ years, 13.4% (7.9-18.9). Sex did not affect age-specific prevalence and there was no difference in prevalence between men and women in any age group. In the regression model, the OR of prevalence increasing by age group was 1.06 (0.92-1.2, P = .37).

Conclusion

This meta-analysis shows the prevalence of subclinical PTC is stable across the lifespan. There is not a higher subclinical PTC prevalence in middle age, in contrast to higher observed incidence rates in this age group. These findings offer unique insights into the prevalence of subclinical PTC and its relationship to age.
History of Adrenal Research: From Ancient Anatomy to Contemporary Molecular Biology
Authors: Miller Walter L , White Perrin C
Published: August 2022

The adrenal is a small, anatomically unimposing structure that escaped scientific notice until 1564 and whose existence was doubted by many until the 18th century. Adrenal functions were inferred from the adrenal insufficiency syndrome described by Addison and from the obesity and virilization that accompanied many adrenal malignancies, but early physiologists sometimes confused the roles of the cortex and medulla. Medullary epinephrine was the first hormone to be isolated (in 1901), and numerous cortical steroids were isolated between 1930 and 1949. The treatment of arthritis, Addison’s disease, and congenital adrenal hyperplasia (CAH) with cortisone in the 1950s revolutionized clinical endocrinology and steroid research. Cases of CAH had been reported in the 19th century, but a defect in 21-hydroxylation in CAH was not identified until 1957. Other forms of CAH, including deficiencies of 3β-hydroxysteroid dehydrogenase, 11β-hydroxylase, and 17α-hydroxylase were defined hormonally in the 1960s. Cytochrome P450 enzymes were described in 1962-1964, and steroid 21-hydroxylation was the first biosynthetic activity associated with a P450. Understanding of the genetic and biochemical bases of these disorders advanced rapidly from 1984 to 2004. The cloning of genes for steroidogenic enzymes and related factors revealed many mutations causing known diseases and facilitated the discovery of new disorders. Genetics and cell biology have replaced steroid chemistry as the key disciplines for understanding and teaching steroidogenesis and its disorders.
A phenotypic rescue approach identifies lineage regionalization defects in a mouse model of DiGeorge syndrome
Authors: Lania Gabriella , Franzese Monica , Adachi Noritaka , Bilio Marchesa , Flore Gemma , Russo Annalaura , D'Agostino Erika , Angelini Claudia , Kelly Robert G. , Baldini Antonio
Published: August 2022

TBX1 is a key regulator of pharyngeal apparatus (PhAp) development. Vitamin B12 (vB12) treatment partially rescues aortic arch patterning defects of Tbx1+/− embryos. Here, we show that it also improves cardiac outflow tract septation and branchiomeric muscle anomalies of Tbx1 hypomorphic mutants. At the molecular level, in vivo vB12 treatment enabled us to identify genes that were dysregulated by Tbx1 haploinsufficiency and rescued by treatment. We found that SNAI2, also known as SLUG, encoded by the rescued gene Snai2, identified a population of mesodermal cells that was partially overlapping with, but distinct from, ISL1+ and TBX1+ populations. In addition, SNAI2+ cells were mislocalized and had a greater tendency to aggregate in Tbx1+/− and Tbx1−/− embryos, and vB12 treatment restored cellular distribution. Adjacent neural crest-derived mesenchymal cells, which do not express TBX1, were also affected, showing enhanced segregation from cardiopharyngeal mesodermal cells. We propose that TBX1 regulates cell distribution in the core mesoderm and the arrangement of multiple lineages within the PhAp.
Sherlock: an open-source data platform to store, analyze and integrate Big Data for computational biologists
Authors: Bohar Balazs , Fazekas David , Madgwick Matthew , Csabai Luca , Olbei Marton , Korcsmáros Tamás , Szalay-Beko Mate
Published: August 2022

In the era of Big Data, data collection underpins biological research more than ever before. In many cases, this can be as time-consuming as the analysis itself. It requires downloading multiple public databases with various data structures, and in general, spending days preparing the data before answering any biological questions. Here, we introduce Sherlock, an open-source, cloud-based big data platform (https://earlham-sherlock.github.io/) to solve this problem. Sherlock provides a gap-filling way for computational biologists to store, convert, query, share and generate biology data while ultimately streamlining bioinformatics data management. The Sherlock platform offers a simple interface to leverage big data technologies, such as Docker and PrestoDB. Sherlock is designed to enable users to analyze, process, query and extract information from extremely complex and large data sets. Furthermore, Sherlock can handle different structured data (interaction, localization, or genomic sequence) from several sources and convert them to a common optimized storage format, for example, the Optimized Row Columnar (ORC). This format facilitates Sherlock’s ability to quickly and efficiently execute distributed analytical queries on extremely large data files and share datasets between teams. The Sherlock platform is freely available on GitHub, and contains specific loader scripts for structured data sources of genomics, interaction and expression databases. With these loader scripts, users can easily and quickly create and work with specific file formats, such as JavaScript Object Notation (JSON) or ORC. For computational biology and large-scale bioinformatics projects, Sherlock provides an open-source platform empowering data management, analytics, integration and collaboration through modern big data technologies.
Communicative Strategy of Self-Presentation in Russian Business Discourse
Authors: Ageeva Yu.
Published: August 2022

The paper analyzes verbal patterns of communicants in the discourse of recruitment. The need to examine patterns and rules of communicative behavior of job applicants highlights the relevance of the study. Its results will enable predicting the success of communication during a job interview and, as a result, in employment. The purpose of the author is to identify and analyze the main and unique verbal tactics of interviewees implemented within the self-presentation as a basic strategy of job candidates. This strategy is represented by a scheme that includes a list of direct and indirect self-presenting actions.

The basic method of the study is an integrative discourse analysis undertaken as part of linguistic pragmatics. The goal of the study, characteristics of its object and subject justify the selection of this approach. The outlined indirect self-presenting actions of the job candidate include the request for communicatively meaningful information and productive self-criticism by which the applicant can demonstrate professionalism and interest in obtaining a position.

The prevalence of indirect self-presenting tactics in the Russian-language recruitment discourse demonstrated for the first time by the study, is linked primarily to the specifics of the Russian mentality and business environment. The materials and findings of the study may be utilized in further linguistic studies and are important for recruiters and all potential applicants.
High Throughput Image Analytics Using Hough Transformation for Wheat Phenotyping
Authors: Kim James Y. , Shin Myung-Na , Lee Ji-Hyun , Jeon Weon-Tai , Cho Seungho
Published: August 2022

Highlights

RGB-based vegetation and leaf area indexes using a smartphone camera.

Geo-rectification of skewed images via row detection using Hough Transformation.

Open-source software to automate the image stitching and plot-level phenotypic metrics extraction.

Abstract. An agricultural field is not always accessible for plant phenotyping with existing mobile platforms due to the limited space and regulated aviation area. Smartphone-triggered ground images were collected on a wheat field that has a limited access to monitor growth conditions of four wheat varieties: Shinyoung (SY), Joseong (JS), Taewoo (TW), and Cheongwoo (CW). For field mapping during the growing season, six sets of the raw images were acquired by a smartphone in an oblique view angle and processed to transform into nadir view images. Algorithms were developed to process the raw tile images for geometric rectification via row detection using Hough Transformation. Stitching software was developed to automate the high throughput image analytics of the skewed tile images into a stitched field image through deskewing, row alignment, overlap trimming, and resizing. Plot-level metrics were extracted to analyze plant growth of the wheat varieties using a gridding method for vegetation and leaf area indexes. The processed images resulted in the successful transformation and consistency of algorithms on image alignment and stitching. Plot-level analysis indicated that SY variety performed superior to the other varieties in both vegetation and leaf area indexes and was significantly different in the canopy coverage from the least performed TW variety. The image analytic methods developed in the study offer a flexible solution to stitch and align tile images by a hand-held camera in both oblique and nadir view via user-friendly interface software for high through plant phenotyping and can be adapted to other stationary or mobile imaging platforms in greenhouse and fields. Keywords: Calibration, Image processing, Phenotyping, Python, Software, Stitching.
Choice of Pipe Material Influences Drain Spacing and System Cost in Subsurface Drainage Design
Authors: Ghane Ehsan
Published: August 2022

Highlights

For 3- or 4-row regular-perforated pipes, the effective radius ranged from 0.3 to 0.9 cm (average 0.6 cm).

For 8-row regular-perforated pipes, the effective radius was 1.9 cm.

The effective radius of sock-wrapped pipes ranged from 5.7 to 6.0 cm (average 5.9 cm).

The 8-row sand-slot pipes had a lower initial system cost than the sock-wrapped pipes.

The 8-row regular-perforated pipes had a lower initial system cost than the 4-row regular-perforated pipes.

Abstract. Knitted-sock envelopes are applied in agricultural subsurface drainage to prevent sediment clogging of the drain pipes. In the United States and Canada, sand-slot pipes are sometimes used as a cheaper alternative to sock-wrapped pipes. However, their initial system cost has not been compared. The main objective of this study was to evaluate the effect of pipe material on drain spacing and initial system cost. First, the theoretical effective radius of each pipe material was estimated. Then, the drain spacing was calculated for each pipe material in a drainage design, such that each pipe would provide the same design drainage rate (i.e., same water removal rate). The results showed that the effective radius of sock-wrapped pipes (average 5.9 cm) was much greater than that of 4-row (average 0.4 cm) and 8-row perforated sand-slot pipes (average 1.6 cm). Rows refer to number of longitudinal rows of perforations. The sock-wrapped pipes considerably increased the effective radius of the pipe by reducing the entrance head loss. Furthermore, the sock-wrapped pipes allowed for a wider drain spacing (ranging from 0.8 to 5.4 m wider) in soil with risk of drain sedimentation, thereby reducing the total length of the lateral drain pipe needed for drainage design compared to both 4- and 8-row sand-slot pipes. The 8-row regular-perforated pipes allowed for a wider optimum drain spacing, thereby reducing the initial system cost in soil without a drain sedimentation issue compared to 4-row regular-perforated pipes. In conclusion, even though the sock-wrapped pipe reduced the total length of the lateral drain pipe, the 8-row sand-slot pipe had a lower initial system cost compared to the sock-wrapped pipe, when designed at the same design drainage rate and drain depth. Keywords: Drain spacing, Effective radius, Entrance resistance, Geotextile, Knitted sock, Perforation.