bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between intravenous iron therapy and short-term mortality risk in older patients undergoing hip fracture surgery: an observational study
Authors: Clemmensen Silas Zacharias , Kragholm Kristian H. , Melgaard Dorte , Hansen Lene T. , Riis Johannes , Cavallius Christian , Mørch Marianne M. , Krogager Maria Lukács
Published: May 2021

Background

Anemia is common among ortho-geriatric hip fracture patients and is associated with prolonged recovery and increased postoperative mortality rate. Intravenous iron seems to increase hemoglobin recovery and reduce the mortality rate in patients undergoing orthopedic surgeries. This study investigated the association between short-term mortality risk and intravenous iron therapy in older patients undergoing hip fracture surgery.

Methods

This observational study included 210 patients undergoing hip fracture surgery from July 2018 to May 2020. These 210 patients were alive and had a hemoglobin ≤ 6.5 mmol/L on the 3rd postoperative day. In May 2019, a local intravenous iron therapy protocol was implemented and recommended intravenous iron (Monofer©) if hemoglobin on the 3rd postoperative day was ≤ 6.5 mmol/L. According to the treatment of postoperative anemia between the 1st and 3rd day post-surgery, the patients were divided into four groups: no treatment (n=52), blood transfusion (n=38), IV Monofer (n=80), and blood transfusion and IV Monofer (n=40). Primary outcome was 30-day mortality post-surgery. The secondary outcome was the impact on hemoglobin level 14–30 days postoperatively. Multivariable Cox regression was used to estimate the 30-day mortality standardized for covariates.

Results

Of 210 patients, 17 (8.1%) died within 30 days after surgery. There was a significantly lower mortality among the patients who received IV Monofer compared to those who received no treatment (HR 0.17, 95% CI [0.03–0.93],P= 0.041). Among the 86 patients with available hemoglobin measurements within 14 to 30 days post-surgery, there was no significant difference in hemoglobin level between the various treatment groups (mean 6.6 mmol/L,P= 0.1165).

Conclusion

IV Monofer on the 3rd postoperative day in older hip fracture patients seemed to reduce 30-day mortality compared with no treatment. No significant differences in hemoglobin levels between 14 and 30 days post-surgery across treatment groups were found, although this was assessed in a subset of patients with available hemoglobin levels warranting further study.
Mosaic duplication of 8q24.1q24.3 detected by chromosomal microarray but not karyotyping in two unrelated fetuses with cardiac defects
Authors: Lin Shaobin , Huang Shufang , Ou Xueling , Gu Heng , Wang Yonghua , Li Ping , Zhou Yi
Published: May 2021

Background

Discordance between traditional cytogenetic and molecular cytogenetic tests is rare but not uncommon. The explanation of discordance between two genetic methods is difficult but especially important for genetic counseling, particularly for prenatal genetic diagnosis.

Case presentation

Two unrelated fetuses were diagnosed with cardiac defects by prenatal ultrasound examination, and invasive cordocentesis was performed to obtain cord blood samples for prenatal genetic diagnosis. For both fetuses, chromosomal microarray analysis (CMA) detected a novel approximately 27-Mb mosaic duplication with a high copy number of approximately six to seven copies on chromosome 8q24.1q24.3 that was not identified by karyotyping. To exclude artificial errors and validate laboratory detection results, multiple procedures including copy number variation sequencing, fluorescence in situ hybridization, and short tandem repeat and single-nucleotide polymorphism genotype comparison were performed, confirming the discordant results between CMA and karyotyping. The potential causes of discordance between CMA and karyotyping using fetal blood lymphocytes are discussed; we suggest that extrachromosomal DNA or cell-free DNA fragmentation originating from certain tumor tissues with 8q24.1q24.3 duplication might deserve further investigation.

Conclusions

This study may be helpful for prenatal evaluation and genetic counseling for subsequent patients with similar mosaic 8q24.1q24.3 duplications. Additionally, more cases and further research are needed to understand whether mosaic 8q24.1q24.3 duplication is associated with certain genetic disorders and to investigate the causes of discordance between molecular and morphological methods.
Advances in drug development for hepatocellular carcinoma: clinical trials and potential therapeutic targets
Authors: Luo Xiang-Yuan , Wu Kong-Ming , He Xing-Xing
Published: May 2021

Although hepatocellular carcinoma (HCC) is one of the deadliest health burdens worldwide, few drugs are available for its clinical treatment. However, in recent years, major breakthroughs have been made in the development of new drugs due to intensive fundamental research and numerous clinical trials in HCC. Traditional systemic therapy schemes and emerging immunotherapy strategies have both advanced. Between 2017 and 2020, the United States Food and Drug Administration (FDA) approved a variety of drugs for the treatment of HCC, including multikinase inhibitors (regorafenib, lenvatinib, cabozantinib, and ramucirumab), immune checkpoint inhibitors (nivolumab and pembrolizumab), and bevacizumab combined with atezolizumab. Currently, there are more than 1000 ongoing clinical trials involving HCC, which represents a vibrant atmosphere in the HCC drug research and development field. Additionally, traditional Chinese medicine approaches are being gradually optimized. This review summarizes FDA-approved agents for HCC, elucidates promising agents evaluated in clinical phase I/II/III trials and identifies emerging targets for HCC treatment. In addition, we introduce the development of HCC drugs in China. Finally, we discuss potential problems in HCC drug therapy and possible future solutions and indicate future directions for the development of drugs for HCC treatment.
Optimizing Nanopore sequencing-based detection of structural variants enables individualized circulating tumor DNA-based disease monitoring in cancer patients
Authors: Valle-Inclan Jose Espejo , Stangl Christina , de Jong Anouk C. , van Dessel Lisanne F. , van Roosmalen Markus J. , Helmijr Jean C. A. , Renkens Ivo , Janssen Roel , de Blank Sam , de Witte Chris J. , Martens John W. M. , Jansen Maurice P. H. M. , Lolkema Martijn P. , Kloosterman Wigard P.
Published: May 2021

Here, we describe a novel approach for rapid discovery of a set of tumor-specific genomic structural variants (SVs), based on a combination of low coverage cancer genome sequencing using Oxford Nanopore with an SV calling and filtering pipeline. We applied the method to tumor samples of high-grade ovarian and prostate cancer patients and validated on average ten somatic SVs per patient with breakpoint-spanning PCR mini-amplicons. These SVs could be quantified in ctDNA samples of patients with metastatic prostate cancer using a digital PCR assay. The results suggest that SV dynamics correlate with and may improve existing treatment-response biomarkers such as PSA.

https://github.com/UMCUGenetics/SHARC.
Pancytopenia as an initial manifestation of prostate cancer: a case report
Authors: da Silva Marcos Antonio Custódio Neto , Manhães Vitor Pimentel Rodrigues , Gasparotto Júnior Luadir , Tsukumo Daniela Miti Lemos , Lalli Cristina Alba
Published: May 2021

Background

Prostate adenocarcinoma is the most frequent cancer type among men, followed by skin cancer. Patients with prostate cancer usually present lower urinary tract symptoms due to tumor involvement. Bone marrow invasion is associated with prostate cancer metastasis and is common if blastic lesions in bones are present but is very rare without a large bone involvement and uncommon as initial presentation.

Case presentation

We present a case of an 86-year-old Caucasian man with bone marrow invasion of prostate cancer without urological or bone-related symptoms and without prostate nodules. His findings were dyspnea, fatigue, and tachycardia. We detail the complete investigation of the case until we found the accurate diagnosis. The patient started treatment, but he had no response and so the oncology team started palliative care.

Conclusion

Bone marrow invasion as an initial manifestation of prostate cancer is not common, especially if no prostatic lesions are found. This report is important to provide additional information about prostate cancer management.
Elective laparoscopic colectomy in a patient 3 weeks after coronavirus disease 2019 infection: a case report
Authors: Tateno Yuki , Harada Kimito , Okamoto Fumiki , Katsuragawa Hideo
Published: May 2021

Background

According to previous reports, surgery is not recommended until at least 4 weeks after the symptoms of coronavirus disease 2019 resolve. However, strong evidence has not been established regarding the optimal timing and preoperative examination for elective laparoscopic colectomy for colorectal cancer in individuals with a previous coronavirus disease 2019 infection.

Case presentation

A 63-year-old Asian man underwent elective laparoscopic colectomy for sigmoid colon cancer 3 weeks after asymptomatic coronavirus disease 2019. The postoperative course was good, and none of the surgical staff was infected with coronavirus disease 2019.

Conclusion

In this patient infected with coronavirus disease 2019 within 4 weeks of surgery, preoperative venous ultrasound of the lower extremities and a chest computed tomography scan were useful examinations for ensuring a safe surgical procedure for the patient and the staff. Surgery within 4 weeks may be possible with careful selection of cases based on thorough preoperative examination. This report may contribute to the development of a consensus on performing safe elective colectomy for colon cancer in persons previously infected with coronavirus disease 2019.
Tetracycline-resistant bacteria and ribosomal protection protein genes in soils from selected agricultural fields and livestock farms
Authors: Nogrado Kathyleen , Unno Tatsuya , Hur Hor-Gil , Lee Ji-Hoon
Published: May 2021

Antibiotic resistance in soil environment has eminently been compared and studied between agricultural and pristine soils, and the role of concentrated animal feeding operations has markedly been recognized as one of the major sources of antibiotic resistance. This study described the tetracycline resistance in small-scale farms in pursuit of presenting its possible role and contribution to the persistence of antibiotic resistance in the environment. Results of the study would render additional information on the occurrence of the ribosomal protection protein (RPP) tet genes among the isolated bacteria from the selected agricultural soils. Four tetracycline resistance and RPP genes were determined in two different agricultural soil settings. Both the culture and molecular method were used to determine and measure tetracycline resistance in soils from arable land and animal house. Results revealed a significantly higher number of culturable antibiotic-resistant bacteria in animal houses than arable lands which was suggestive of higher antibiotic resistance in areas where there was direct administration of the antibiotics. However, quantification of the gene copy numbers in the agricultural soils indicated a different result. Higher gene copy number of tetO was determined in one animal house (IAH-3), while the two other tet genes tetQ and tetW were found to be higher in arable lands. Of the total 110 bacterial isolates, tetW gene was frequently detected, while tetO gene was absent in any of the culturable bacterial isolates. Principal component analysis of occurrence and gene copy number of RPP tet genes tetO, tetQ, and tetW also revealed highest abundance of RPP tet genes in the manure and arable soils. Another important highlight of this study was the similarity of the RPP tet genes detected in the isolated bacteria from the agricultural soils to the identified RPP tet genes among pathogenic bacteria. Some of the tetracycline-resistant bacterial isolates were also multidrug resistant as it displayed resistance to tetracycline, erythromycin, and streptomycin using disk diffusion testing.
The acceptability of yellow mealworm as chicken feed: a case study of small-scale farmers in South Africa
Authors: Selaledi Letlhogonolo , Maake Matome , Mabelebele Monnye
Published: May 2021

Background

Small-scale poultry farming plays a major role as a source of income for farmers through the sale of birds and eggs. Furthermore, in households’ poultry products are a valuable source of protein in the diet—especially in low-income communities. However, these farmers are facing a challenge with the rising cost of conventional feed. Climate change and global warming play a role in changing farming activities and affecting household food security. Therefore, replacing traditional ingredients with insects in chicken diets is gaining popularity worldwide. The purpose of this study was to assess the willingness of small-scale poultry farmers to adopt the use of yellow mealworm in diets for chickens. A total number of 107 farmers in the City of Tshwane Metropolitan Municipality were selected using snowball sampling and were interviewed face to face using a semi-structured questionnaire.

Results

Descriptive statistics and binary logistic regression were used to analyse the data. The results of the study showed that 72% of respondents, the majority of whom were male, were willing to adopt mealworm as poultry feed. About 51% of the participants were willing to eat chicken that was reared using mealworms, even though 85% had not seen mealworms before. Furthermore, it was found that farmers who used mixed corn and who had secondary education were more willing to adopt mealworms as an alternative protein source in chicken feed.

Conclusion

Small-scale poultry farmers in Tshwane accept the use of mealworm as chicken feed. It is recommended that the early adopters of mealworms as poultry feed be profiled so that communication strategies can be developed to deal with the fears and attitudes of farmers who are not willing to adopt mealworms as poultry feed. Since the majority of the farmers who are willing to adopt mealworm had secondary education, it would be beneficial if small-scale poultry farmers are educated about the benefits of using yellow mealworm as a substitute in poultry feed.
Identifying biases and their potential solutions in human microbiome studies
Authors: Nearing Jacob T. , Comeau André M. , Langille Morgan G. I.
Published: May 2021

Advances in DNA sequencing technology have vastly improved the ability of researchers to explore the microbial inhabitants of the human body. Unfortunately, while these studies have uncovered the importance of these microbial communities to our health, they often do not result in similar findings. One possible reason for the disagreement in these results is due to the multitude of systemic biases that are introduced during sequence-based microbiome studies. These biases begin with sample collection and continue to be introduced throughout the entire experiment leading to an observed community that is significantly altered from the true underlying microbial composition. In this review, we will highlight the various steps in typical sequence-based human microbiome studies where significant bias can be introduced, and we will review the current efforts within the field that aim to reduce the impact of these biases.
The microbiome and mosquito vectorial capacity: rich potential for discovery and translation
Authors: Cansado-Utrilla Cintia , Zhao Serena Y. , McCall Philip J. , Coon Kerri L. , Hughes Grant L.
Published: May 2021

Microbiome research has gained considerable interest due to the emerging evidence of its impact on human and animal health. As in other animals, the gut-associated microbiota of mosquitoes affect host fitness and other phenotypes. It is now well established that microbes can alter pathogen transmission in mosquitoes, either positively or negatively, and avenues are being explored to exploit microbes for vector control. However, less attention has been paid to how microbiota affect phenotypes that impact vectorial capacity. Several mosquito and pathogen components, such as vector density, biting rate, survival, vector competence, and the pathogen extrinsic incubation period all influence pathogen transmission. Recent studies also indicate that mosquito gut-associated microbes can impact each of these components, and therefore ultimately modulate vectorial capacity. Promisingly, this expands the options available to exploit microbes for vector control by also targeting parameters that affect vectorial capacity. However, there are still many knowledge gaps regarding  mosquito–microbe interactions  that need to be addressed in order to exploit them efficiently. Here, we review current evidence of impacts of the microbiome on aspects of vectorial capacity, and we highlight likely opportunities for novel vector control strategies and areas where further studies are required.
The effectiveness of E-learning in continuing medical education for tuberculosis health workers: a quasi-experiment from China
Authors: Wang Zi-Yue , Zhang Li-Jie , Liu Yu-Hong , Jiang Wei-Xi , Jia Jing-Yun , Tang Sheng-Lan , Liu Xiao-Yun
Published: May 2021

Background

Given the context of rapid technological change and COIVD-19 pandemics, E-learning may provide a unique opportunity for addressing the challenges in traditional face-to-face continuing medical education (CME). However, the effectiveness of E-learning in CME interventions remains unclear. This study aims to evaluate whether E-learning training program can improve TB health personnel’s knowledge and behaviour in China.

Methods

This study used a convergent mixed method research design to evaluate the impact of E-learning programs for tuberculosis (TB) health workers in terms of knowledge improvement and behaviour change during the China-Gates TB Project (add the time span). Quantitative data was collected by staff surveys (baseline n = 555; final n = 757) and management information systems to measure the demographic characteristics, training participation, and TB knowledge. Difference-in-difference (DID) and multiple linear regression models were employed to capture the effectiveness of knowledge improvement. Qualitative data was collected by interviews (n = 30) and focus group discussions (n = 44) with managers, teachers, and learners to explore their learning experience.

Results

Synchronous E-learning improved the knowledge of TB clinicians (average treatment effect, ATE: 7.3 scores/100, P = 0.026). Asynchronous E-learning has a significant impact on knowledge among primary care workers (ATE: 10.9/100, P < 0.001), but not in clinicians or public health physicians. Traditional face-to-face training has no significant impact on all medical staff. Most of the learners (57.3%) agreed that they could apply what they learned to their practice. Qualitative data revealed that high quality content is the key facilitator of the behaviour change, while of learning content difficulty, relevancy, and hardware constraints are key barriers.

Conclusions

The effectiveness of E-learning in CME varies across different types of training formats, organizational environment, and target audience. Although clinicians and primary care workers improved their knowledge by E-learning activities, public health physicians didn’t benefit from the interventions.
Early life predictors of positive change during the coronavirus disease pandemic
Authors: Bleil Maria E. , Appelhans Bradley M. , Thomas Alexis S. , Gregorich Steven E. , Marquez Neal , Roisman Glenn I. , Booth-LaForce Cathryn , Crowder Kyle
Published: May 2021

Background

The COVID-19 pandemic is a crisis unprecedented in its size and scope. Yet studies of resilience suggest most individuals will successfully negotiate this challenge and some may even experience growth and positive change. Some evidence suggests that the capacity to enact positive change in the face of adversity may be shaped by early life experiences.

Methods

In a subset of 374 participants (57% female, mean age = 29 years) in the Study of Early Child Care and Youth Development (SECCYD), a longitudinal, birth cohort, prospective models were tested to determine whether early life adversities in family and neighborhood contexts predict positive change events in response to the COVID-19 pandemic. Childhood family and neighborhood contexts were assessed using a combination of self-report questionnaires and US Census data. Adulthood positive change events (e.g., becoming more appreciative of things usually taken for granted) were assessed using the Epidemic-Pandemic Impacts Inventory (EPII).

Results

In regression analyses, neighborhood disadvantage in childhood, measured both by objective and subjective assessments, predicted a higher number of positive change events in response to the COVID-19 pandemic (β = .18, p = .004 and β = .15, p = .006, respectively). Examination of the positive change event subscales showed neighborhood disadvantage in childhood predicted increases in events related to ‘perspective taking and charitable giving’ (β = .20, p = .022 and β = .17, p = .002, respectively) and improved ‘social relationships’ (β = .18, p = .004 and β = .13, p = .020, respectively), but not to positive ‘health behaviors’ (ps > .05). All associations were independent of sociodemographic factors and childhood family dysfunction.

Conclusions

Findings suggest that neighborhood disadvantage in childhood may shape prosocial responses to stress in adulthood, potentially through early life adaptions to stress that are protective when facing adversity. There are several notable implications of the study findings. Although adversity in early life has clear negative impacts, it is possible that adversity experiences may also provide opportunities to develop adaptive strategies that foster resilience and growth when facing stress. Intervention efforts should consider leveraging such stress-adapted strengths to reduce the many negative impacts of early life adversity.
Extract of white sweet potato tuber against TNF-α-induced insulin resistance by activating the PI3K/Akt pathway in C2C12 myotubes
Authors: Shyur Lie-Fen , Varga Viola , Chen Chiao-Ming , Mu Shu-Chi , Chang Yu-Chih , Li Sing-Chung
Published: May 2021

Background

White sweet potato (WSP; Ipomoea batatas L. Simon No. 1) has many potential beneficial effects on metabolic control and diabetes-related insulin resistance. The improvement of insulin resistance by WSP tuber extracts on glucose uptake were not investigated in C2C12 myoblast cells.

Results

WSP tuberous ethanol extract (WSP-E) was partitioned with ethyl-acetate and water to obtain ethyl-acetate layer (WSP-EA) and water layer (WSP-EW). The WSP-EA shows the highest total phenolic contents and highest antioxidant activity by Folin-Ciocalteu and (2,2-diphenyl-1-picryl-hydrazyl-hydrate, DPPH) assay, respectively. After low concentration horse serum on differentiation inducement of C2C12 myoblasts into mature myotubes, the cells were treated with TNF-α to induce insulin resistance. WSP-EA and WSP-EW extracts increased the uptake of fluorescence glucose analogue (2-[N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino]-2-deoxy-d-glucose, 2-NBDG) in a dose-dependent manner as examined by flow cytometry. The WSP-EA enhanced glucose uptake by activation of phosphorylation of IR (pIR), IRS-1 (pIRS-1) and Akt (pAkt) involved in PI3K (phosphatidylinositol 3-kinase)/protein kinase B (Akt) pathway, also upregulated glucose transporter 4 (GLUT4) expression in myotubes.

Conclusions

WSP-EA enhanced the glucose uptake in C2C12 myotubes through upregulating the PI3K/Akt pathway. The in vitro data reveal that WSP tuber extracts has potential applications to improve insulin resistance in diabetes.
Predictive modelling for COVID-19 outbreak control: lessons from the navy cluster in Sri Lanka
Authors: Wijesekara N. W. A. N. Y. , Herath Nayomi , Kodituwakku K. A. L. C. , Herath H. D. B. , Ginige Samitha , Ruwanpathirana Thilanga , Kariyawasam Manjula , Samaraweera Sudath , Herath Anuruddha , Jayawardena Senarupa , Gamge Deepa
Published: May 2021

In response to an outbreak of coronavirus disease 2019 (COVID-19) within a cluster of Navy personnel in Sri Lanka commencing from 22nd April 2020, an aggressive outbreak management program was launched by the Epidemiology Unit of the Ministry of Health. To predict the possible number of cases within the susceptible population under four social distancing scenarios, the COVID-19 Hospital Impact Model for Epidemics (CHIME) was used. With increasing social distancing, the epidemiological curve flattened, and its peak shifted to the right. The observed or actually reported number of cases was above the projected number of cases at the onset; however, subsequently, it fell below all predicted trends. Predictive modelling is a useful tool for the control of outbreaks such as COVID-19 in a closed community.
Gut microbiota of frugo-folivorous sifakas across environments
Authors: Greene Lydia K. , Blanco Marina B. , Rambeloson Elodi , Graubics Karlis , Fanelli Brian , Colwell Rita R. , Drea Christine M.
Published: May 2021

Background

Captive animals, compared to their wild counterparts, generally harbor imbalanced gut microbiota owing, in part, to their altered diets. This imbalance is particularly striking for folivores that fundamentally rely on gut microbiota for digestion, yet rarely receive sufficient dietary fiber in captivity. We examine the critically endangered Coquerel’s sifaka (Propithecus coquereli), an anatomically specialized, rather than facultative, folivore that consumes a seasonal frugo-folivorous diet in the wild, but is provisioned predominantly with seasonal foliage and orchard vegetables in captivity. Using amplicon and metagenomic sequencing applied to fecal samples collected from two wild and one captive population (each comprising multiple groups), we clarify how dietary variation underlies the perturbational effect of captivity on the structure and function of this species’ gut microbiota.

Results

The gut microbiota of wild sifakas varied by study population, most notably in community evenness and in the abundance of diet-associated microbes fromPrevotellaeceaeandLachnospiraceae. Nevertheless, the differences among wild subjects were minor compared to those evident between wild and captive sifakas: Unusually, the consortia of captive sifakas were the most diverse, but lacked representation of endemicBacteroidetesand metagenomic capacity for essential amino-acid biosynthesis. Instead, they were enriched for complex fiber metabolizers from theFirmicutesphylum, for archaeal methanogens, and for several metabolic pathways putatively linked to plant fiber and secondary compound metabolism.

Conclusions

The relatively minor differences in gut microbial structure and function between wild sifaka populations likely reflect regional and/or temporal environmental variability, whereas the major differences observed in captive conspecifics, including the loss of endemic microbes, but gain in low-abundance taxa, likely reflect imbalanced or unstable consortia. Indeed, community perturbation may not necessarily entail decreased community diversity. Moreover, signatures of greater fiber degradation indicate that captive sifakas consume a more fibrous diet compared to their wild counterparts. These results do not mirror those typically reported for folivores and herbivores, suggesting that the direction and strength of captivity-induced ‘dysbiosis’ may not be universal across species with similar feeding strategies. We propose that tailored, species-specific dietary interventions in captivity, aimed at better approximating naturally foraged diets, could functionally ‘rewild’ gut microbiota and facilitate successful management of diverse species.
Predictive factors of ovarian response to GnRH antagonist stimulation protocol: AMH and age are potential candidates
Authors: Laqqan Mohammed M. , Yassin Maged M.
Published: May 2021

Background

Prediction of ovarian response prior to the ovarian stimulation cycle is useful in determining the optimal starting dose of recombinant follicle-stimulating hormone (r-FSH). This study was designed to (I) evaluate which of the following parameters (age, AMH, and FSH) can be used as a predictor of ovarian response to GnRH antagonist stimulation protocol, (II) determine the cutoff value of AMH and age for predicting poor and high ovarian response, and (III) investigate the relationship between age, AMH level, and other clinical parameters. It is a retrospective study. A total of 318 women with a mean age of 28.2 ± 5.9 years old were included in this study. Hormone levels (FSH, LH, PRL, E2, and AMH) and the number of collected oocytes were determined. Based on the number of retrieved oocytes, the participants were divided into three groups: poor response (oocytes < 4, n= 51), normal response (oocytes 4–14, n= 192), and high response (oocytes > 14, n= 75).

Results

A significant increase has been found in AMH level and number of retrieved oocytes and mature oocytes from low to normal and high ovarian response group (P < 0.001). Also, the age in the poor ovarian response group was significantly greater than normal and high ovarian response groups (P < 0.001). A significant positive correlation has been found between the number of retrieved oocytes and mature oocytes and level of AMH (P < 0.001). The receiver operating characteristic (ROC) curves showed that both AMH and age had the highest accuracy in the prediction of poor ovarian response with a cutoff value < 1.45 and > 31.5 years, respectively. Additionally, the ROC analysis has shown that the AMH had the highest accuracy, followed by age in the prediction of high ovarian response with a cutoff value > 3.55 and < 27.5 years, respectively.

Conclusions

This study demonstrates that AMH level and women’s age may be used as potential predictors of ovarian response to GnRH antagonist stimulation protocol.
Direct Comparison of the Prediction of the Unbound Brain-to-Plasma Partitioning Utilizing Machine Learning Approach and Mechanistic Neuropharmacokinetic Model
Authors: Kosugi Yohei , Mizuno Kunihiko , Santos Cipriano , Sato Sho , Hosea Natalie , Zientek Michael
Published: May 2021

The mechanistic neuropharmacokinetic (neuroPK) model was established to predict unbound brain-to-plasma partitioning (Kp,uu,brain) by considering in vitro efflux activities of multiple drug resistance 1 (MDR1) and breast cancer resistance protein (BCRP). Herein, we directly compare this model to a computational machine learning approach utilizing physicochemical descriptors and efflux ratios of MDR1 and BCRP-expressing cells for predicting Kp,uu,brain in rats. Two different types of machine learning techniques, Gaussian processes (GP) and random forest regression (RF), were assessed by the time and cluster-split validation methods using 640 internal compounds. The predictivity of machine learning models based on only molecular descriptors in the time-split dataset performed worse than the cluster-split dataset, whereas the models incorporating MDR1 and BCRP efflux ratios showed similar predictivity between time and cluster-split datasets. The GP incorporating MDR1 and BCRP in the time-split dataset achieved the highest correlation (R2 = 0.602). These results suggested that incorporation of MDR1 and BCRP in machine learning is beneficial for robust and accurate prediction. Kp,uu,brain prediction utilizing the neuroPK model was significantly worse compared to machine learning approaches for the same dataset. We also investigated the predictivity of Kp,uu,brain using an external independent test set of 34 marketed drugs. Compared to machine learning models, the neuroPK model showed better predictive performance with R2 of 0.577. This work demonstrates that the machine learning model for Kp,uu,brain achieves maximum predictive performance within the chemical applicability domain, whereas the neuroPK model is applicable more widely beyond the chemical space covered in the training dataset.
Cherry River
Authors: Strom Mary Ellen , Doyle Shane
Published: May 2021

The multimedia exhibition Cherry River, Where the Rivers Mix was presented to audiences in August 2018 at the Missouri Headwaters State Park in Three Forks, Montana. Long before the European invasion across the Atlantic, the headwaters, or the confluence of three forks of the Missouri River, was a crossroads for Northern Plains Indians. The place-based project, Cherry River, created by artist Mary Ellen Strom and Native American researcher Shane Doyle, was produced by Mountain Time Arts, a collaborative arts and culture organization in southwestern Montana. In an effort to analyze the site, Mountain Time Arts convened a diverse group of participants. Their research question became, What does it take to change the name of a river? After six months of research, the project centered on the act of changing the name of the East Gallatin River back to the Indigenous Crow name Cherry River. The name Cherry River honors and describes the numerous chokecherry trees growing on the river’s banks that provide sustenance for wildlife and venerates Indigenous history, the ecology of running water, and riparian systems in the Northwest. The rise of interest in the rights of Indigenous people in North America aligns with many of Okwui Enwezor’s groundbreaking initiatives around the world. This assemblage of images, poetry, and first-person narratives is an example of the kind of practice in dialogue with the legacy of Enwezor’s decolonial actions and innovative use of curatorial strategies in several groundbreaking exhibitions to confront the “complex predicaments of contemporary art in a time of profound historical change and global transformation.” While Enwezor was neither an explicit source of inspiration nor invoked for the Cherry River project, the futures of Enwezor are palpable in this anticolonial project restoring the past to reimagine the present.
Overlap of vitamin A and vitamin D target genes with CAKUT-related processes
Authors: Ozisik Ozan , Ehrhart Friederike , Evelo Chris T. , Mantovani Alberto , Baudot Anaı̈s
Published: May 2021

Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) are a group of abnormalities affecting the kidneys and their outflow tracts, which include the ureters, the bladder, and the urethra. CAKUT patients display a large clinical variability as well as a complex aetiology, as only 5% to 20% of the cases have a monogenic origin. It is thereby suspected that interactions of both genetic and environmental factors contribute to the disease. Vitamins are among the environmental factors that are considered for CAKUT aetiology. In this study, we collected vitamin A and vitamin D target genes and computed their overlap with CAKUT-related gene sets. We observed significant overlaps between vitamin A target genes and CAKUT causal genes, or with genes involved in renal system development, which indicates that an excess or deficiency of vitamin A might be relevant to a broad range of urogenital abnormalities.
Scientific research and innovation response to the COVID-19 pandemic in Peru
Authors: Moya-Salazar Jeel , Gomez-Saenz Lucia , Cañari Betsy , Contreras-Pulache Hans
Published: May 2021

Background: COVID-19 has shaken countries at all levels, putting public health at risk. Global efforts have allocated funding for the development of research for the development of vaccines, digital tools, epidemiologic, social, and economic studies. Although these efforts have been developed worldwide, not all countries have prioritized the same topics, and may have a different impact on solving problems and containing the spread of COVID-19.

Methods: A descriptive study was conducted with secondary data of "Special Projects COVID-19” in order to analyze the prioritization of proposals and projects to Peruvian needs in the face of pandemic. Two calls were made by the Peruvian research council (CONCyTec); the first with five areas and second with seven. The global amounts financed by each call were 342,857 USD (1,200,000 soles) and 700,000 USD (1,750,000 soles), respectively.

Results: A total of 1,101 research projects were presented, 600 (54.5%) in the first call. In this call, 176 (29.3%) projects were from the technological development and innovation and 29 were winners (with a global budget of 1,711,907.25 USD /6,077,270.75 soles). In the second call, 120 (23.9%) projects were from the area of Social and economic research and 21 were winners (global budget of 1,284,002.25 USD/558,208.55 soles) (p=0.043). The largest proportion of winning projects in both calls was 12 (41.4%) in Technological developments and innovation, then five (17.2%) each in telehealth and mobile health, and epidemiological and social studies. Across both calls, 214 (55.8%) and 160 (51.9%) projects were of private organizations and universities, respectively.

Conclusions: This research shows ~2% of rapid response "Special Projects COVID-19” were financed by the CONCyTec call with over a million dollars of funds. Although the main topics were technological innovation, detection systems, and vaccines, these priorities have not had a global impact on the epidemiological development of the pandemic in Peru.
Isolation of active Averrhoa bilimbi phytocompounds corresponding to brown adipocytes stimulation
Authors: Hamzah Mohamad Faiz , Amanah Azimah , Lau Wai Kwan
Published: May 2021

Averrhoa bilimbi is a fast-growing tree widely found in countries of tropical Asia. Due to easy accessibility and traditional knowledge, various parts of this plant are adopted as folk medicine and a natural health remedy. Recently, beneficial effects of bilimbi in combating obesity including its potential antihyperlipidemic and hypoglycemic activities have been discovered. This paper reports the successive isolation and purification of bioactive compounds from the leaf of bilimbi that corresponds to brown adipocyte activation. Bilimbi ethanolic extract underwent bioassay-guided partitioning and fractionation. The n-hexane partition exhibited highest brown adipogenesis potential via adipomyocytes differentiation. Further isolation of this active partition yielded 10 fractions. Active fractions with the highest brown adipogenesis potential were further evaluated via the adipomyocytes assay. Chemical structures of the constituents were elucidated by gas chromatography-mass spectrometry (GC-MS). Major phytocomponents in the n-hexane partition include hexadecanoic acid, phytol, 9-Octadecenoic acid (Z)- and squalene.
Case Report: SARS-CoV-2 as an unexpected causal agent of isolated febrile hepatitis
Authors: Filippidis Paraskevas , van Ouwenaller Francois , Cerutti Alberto , Geiger-Jacquod Anaïs , Sempoux Christine , Pantaleo Giuseppe , Moradpour Darius , Lamoth Frederic
Published: May 2021

Background: Respiratory symptoms and pneumonia are the predominant features of Coronavirus disease 2019 (COVID-19) due to emerging SARS-CoV-2 virus, but extrapulmonary manifestations are also observed. For instance, some degree of liver injury has been described among patients requiring hospital admission for severe COVID-19. However, acute febrile hepatitis as an initial or predominant manifestation of COVID-19 has been rarely reported.

Case presentation: A 34-year-old man without underlying medical conditions presented with fever of unknown origin for two weeks in the absence of respiratory symptoms or other complaints. Laboratory testing revealed isolated acute hepatitis, for which an extensive microbiological work-up did not reveal identification of the causal agent. PCR testing for SARS-CoV-2 on a nasopharyngeal swab was negative on two occasions and initial serology for SARS-CoV-2 (at 15 days from symptoms onset) was also negative. However, repeated SARS-CoV-2 serological testing at 30 days demonstrated seroconversion leading to the diagnosis of COVID-19-related hepatitis. The patient's condition progressively improved, while transaminases steadily declined and eventually returned back to normal within 30 days.

Conclusions: We describe here a unique case of SARS-CoV-2 isolated febrile hepatitis in a young and previously healthy man, which was diagnosed by demonstration of seroconversion, while PCR screening was negative. This case report highlights the role of repeated serological testing for the diagnosis of extrapulmonary manifestations of COVID-19.
The impact of COVID-19 on clinical research: the PIPPRA and MEDRA experience
Authors: Larkin Louise , Raad Tala , Moses Anusha , Fraser Alexander , Gallagher Stephen , Appel Esbensen Bente , Glynn Liam , Griffin Anne , Tierney Audrey C , Kennedy Norelee
Published: May 2021

Background: Coronavirus disease 2019 (COVID-19) has had a significant impact on clinical research. This paper aims to provide an insight into how the COVID-19 pandemic, associated public health restrictions and international guidance on the conduct of clinical research impacted two clinical rheumatology research trials - the Physiotherapist-led Intervention to Promote Physical Activity in Rheumatoid Arthritis (PIPPRA) and the MEDiterranean diet in Rheumatoid Arthritis (MEDRA) projects.

Methods: The March 2019 public health restrictions imposed to mitigate the risk of COVID-19 occurred at a time when PIPPRA was in the process of delivering assessment and intervention on a face-to-face basis (n=48) and MEDRA had commenced recruitment. Participants in PIPPRA and MEDRA had a diagnosis of rheumatoid arthritis, with some being immunosuppressed and thus at a higher risk for COVID-19. The decision-making processes of both trials is outlined to demonstrate the required amendments to continue in the context of the COVID-19 pandemic.

Results: Amendments to PIPPRA and MEDRA trial protocols were agreed and received ethical and funder approval. Both trials switched from a face-to-face delivery to a telehealth using online platforms. The PIPPRA study was paused for five months (April-August 2020), resulting in n=33 (60%) deviations from assessment protocol. MEDRA switched from face-to-face to online recruitment with 20% (n=35/44) deviation in recruitment. Of the n=18 participants who consented to participating in a face-to-face trial, just n=2 (11%) opted to engage with telehealth delivery of the intervention. MEDRA assessment and intervention deviations were 100% as no sessions were completed as planned in 2020.

Conclusions: The COVID-19 pandemic has severely impacted the PIPPRA and MEDRA clinical trials. Moving face-to-face clinical research to telehealth delivery may not be the panacea it is purported to be. Our experiences may be of benefit to researchers, clinicians, and funders in seeking to continue clinical research during a global pandemic.
Feasibility and validation of trans-valvular flow derived by four-dimensional flow cardiovascular magnetic resonance imaging in patients with atrial fibrillation
Authors: Mills Mark T , Grafton-Clarke Ciaran , Williams Gareth , Gosling Rebecca C , Al Baraikan Abdulaziz , Kyriacou Andreas L , Morris Paul D , Gunn Julian P , Swoboda Peter P , Levelt Eylem , Tsampasian Vasiliki , van der Geest Rob J , Swift Andrew J , Greenwood John P , Plein Sven , Vassiliou Vass , Garg Pankaj
Published: May 2021

Background: Four-dimensional (4D) flow cardiovascular magnetic resonance imaging (MRI) is an emerging technique used for intra-cardiac blood flow assessment. The role of 4D flow cardiovascular MRI in the assessment of trans-valvular flow in patients with atrial fibrillation (AF) has not previously been assessed. The purpose of this study was to assess the feasibility, image quality, and internal validity of 4D flow cardiovascular MRI in the quantification of trans-valvular flow in patients with AF.

Methods: Patients with AF and healthy controls in sinus rhythm underwent cardiovascular MRI, including 4D flow studies. Quality assurance checks were done on the raw data and streamlines. Consistency was investigated by trans-valvular flow assessment between the mitral valve (MV) and the aortic valve (AV).

Results: Eight patients with AF (88% male, mean age 62±13 years, mean heart rate (HR) 83±16 beats per minute (bpm)) were included and compared with ten healthy controls (70% male, mean age 41±20 years, mean HR 68.5±9 bpm). All scans were of either good quality with minimal blurring artefacts, or excellent quality with no artefacts. No significant bias was observed between the AV and MV stroke volumes in either healthy controls (–4.8, 95% CI –15.64 to 6.04; P=0.34) or in patients with AF (1.64, 95% CI –4.7 to 7.94; P=0.56). A significant correlation was demonstrated between MV and AV stroke volumes in both healthy controls (r=0.87, 95% CI 0.52 to 0.97; P=0.001) and in AF patients (r=0.82, 95% CI 0.26 to 0.97; P=0.01).

Conclusions: In patients with AF, 4D flow cardiovascular MRI is feasible with good image quality, allowing for quantification of trans-valvular flow.
The genome sequence of the Norway rat, Rattus norvegicus Berkenhout 1769
Authors: Howe Kerstin , Dwinell Melinda , Shimoyama Mary , Corton Craig , Betteridge Emma , Dove Alexander , Quail Michael A. , Smith Michelle , Saba Laura , Williams Robert W. , Chen Hao , Kwitek Anne E. , McCarthy Shane A. , Uliano-Silva Marcela , Chow William , Tracey Alan , Torrance James , Sims Ying , Challis Richard , Threlfall Jonathan , Blaxter Mark
Published: May 2021

We present a genome assembly from an individual male Rattus norvegicus (the Norway rat; Chordata; Mammalia; Rodentia; Muridae). The genome sequence is 2.44 gigabases in span. The majority of the assembly is scaffolded into 20 chromosomal pseudomolecules, with both X and Y sex chromosomes assembled. This genome assembly, mRatBN7.2, represents the new reference genome for R. norvegicus and has been adopted by the Genome Reference Consortium.
Recommendations on Occupational Risk Assessment Matrix Development
Authors: Chernyy K. , Belokrylova Ekaterina
Published: May 2021

The matrix method is often used for occupational risk assessment. In this paper have been considered the matrix method’s use features, as well as have been highlighted its advantages and disadvantages. Have been presented recommendations on the risk matrix development, and criteria for categorization of occupational risk’s attributes – the effect consequences severity of hazard and its feasibility.

The proposed approach to consequences severity categorization is accorded with rules and regulations regarding the severity of harm to human health, which in return facilitates mitigation the degree of uncertainty and subjectivity of the assessment results.

The grading of categories for hazard feasibility is based on well-known scientific and practical approaches. Has been performed the generalization of scientific data on the hazard feasibility categorization, and have been proposed universal criteria descriptors, which allow assess the considered hazard objectively and all round, and determine the necessary category for this hazard feasibility. It has been pointed to subjective perception of categories names in final estimating of occupational risk levels, and has been proposed to use the concepts of occupational risk levels, which based on the priority relating to risk respond measures.

The proposed approaches facilitate increase of quality and effectiveness of matrix method use in estimating of occupational risk levels.
Building general practice teams
Authors: Hancock Dave
Published: May 2021

There are many sources of team-building advice, but the latest contribution from The King's Fund stands out as a well researched and authoritative guide. Dave Hancock highlights a few key points