bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and aetiologies of anaemia among first trimester pregnant women in Sri Lanka; the need for revisiting the current control strategies
Authors: Amarasinghe Gayani Shashikala , Agampodi Thilini Chanchala , Mendis Vasana , Malawanage Krishanthi , Kappagoda Chamila , Agampodi Suneth Buddhika
Published: January 2022

Background

The Sustainable development goals, which focus strongly on equity, aim to end all forms of malnutrition by 2030. However, a significant cause of intergenerational transfer of malnutrition, anaemia in pregnancy, is still a challenge. It is especially so in the low- and middle-income settings where possible context-specific aetiologies leading to anaemia have been poorly explored. This study explores the prevalence of etiological factors significantly contributing to anaemia in pregnancy in Sri Lanka, a lower-middle-income country with a high prevalence of malnutrition albeit robust public health infrastructure.

Methods

All first-trimester pregnant women registered in the public maternal care programme in the Anuradhapura district from July to September 2019 were invited to participate in Rajarata Pregnancy Cohort (RaPCo). After a full blood count analysis, high-performance liquid chromatography, peripheral blood film examination, serum B12 and folate levels were performed in anaemic participants, guided by an algorithm based on the red cell indices in the full blood count. In addition, serum ferritin was tested in a random subsample of 213 participants. Anaemic women in this subsample underwent B12 and folate testing.

Results

Among 3127 participants, 14.4% (95%CI 13.2–15.7,n = 451) were anaemic. Haemoglobin ranged between 7.4 to 19.6 g/dl. 331(10.6%) had mild anaemia. Haemoglobin ≥13 g/dl was observed in 39(12.7%). Microcytic, normochromic-normocytic, hypochromic-normocytic and macrocytic anaemia was observed in 243(54%), 114(25.3%), 80(17.8%) and two (0.4%) of full blood counts in anaemic women, respectively. Microcytic anaemia with a red cell count ≥5 * 106/μl demonstrated a 100% positive predictive value for minor haemoglobinopathies. Minor hemoglobinopathies were present in at least 23.3%(n = 105) of anaemic pregnant women. Prevalence of iron deficiency, B12 deficiency and Southeast Asian ovalocytosis among the anaemic was 41.9% (95%CI 26.4–59.2), 23.8% (95%CI 10.6–45.1) and 0.9% (95%CI 0.3–2.3%), respectively. Folate deficiency was not observed.

Conclusion

Even though iron deficiency remains the primary cause, minor hemoglobinopathies, B 12 deficiency and other aetiologies substantially contribute to anaemia in pregnancy in this study population. Public health interventions, including screening for minor hemoglobinopathies and multiple micronutrient supplementation in pregnancy, should be considered in the national programme for areas where these problems have been identified.
Factors associated with changes in adequate antenatal care visits among pregnant women aged 15-49 years in Tanzania from 2004 to 2016
Authors: Kasagama Elizabeth , Todd Jim , Renju Jenny
Published: January 2022

Background

Antenatal care (ANC) is crucial for the health of the mother and unborn child as it delivers highly effective health interventions that can prevent maternal and newborn morbidity and mortality. In 2002, the World Health Organization (WHO) recommended a minimum of four ANC visits for a pregnant woman with a positive pregnancy during the entire gestational period. Tanzania has sub-optimal adequate (four or more) ANC visits, and the trend has been fluctuating over time. An understanding of the factors that have been contributing to the fluctuating trend over years is pivotal in increasing the proportions of pregnant women attaining adequate ANC visits in Tanzania.

Methods

The study used secondary data from Tanzania Demographic Health Survey (TDHS) from 2004 to 2016. The study included 17976 women aged 15-49 years. Data were analyzed using Stata version 14. Categorical and continuous variables were summarized using descriptive statistics and weighted proportions. A Poisson regression analysis was done to determine factors associated with adequate ANC visits. To determine factors associated with changes in adequate ANC visits among pregnant women in Tanzania from 2004 to 2016, multivariable Poisson decomposition analysis was done.

Results

The overall proportion of women who had adequate ANC visits in 2004/05, 2010 and 2015/16 was 62, 43 and 51% respectively. The increase in the proportion of women attaining adequate ANC from 2010 to 2015/16 was mainly, 66.2% due to changes in population structure, thus an improvement in health behavior. While 33.8% was due to changes in the mother’s characteristics. Early initiation of first ANC visit had contributed 51% of the overall changes in adequate ANC attendance in TDHS 2015/16 survey.

Conclusion

Early ANC initiation has greatly contributed to the increased proportion of pregnant women who attain four or more ANC visits overtime. Interventions on initiating the first ANC visit within the first twelve weeks of pregnancy should be a priority to increase proportion of women with adequate ANC visit.
Prevalence and factors associated with unplanned pregnancy in The Gambia: findings from 2018 population-based survey
Authors: Barrow Amadou , Jobe Amienatta , Barrow Sulayman , Touray Ebrima , Ekholuenetale Michael
Published: January 2022

Background

Unplanned pregnancy is a public health issue that has detrimental implications for the mother and baby alike. However, few studies have been conducted in The Gambia on this subject. As a result, the prevalence of unplanned pregnancy among women of reproductive age in The Gambia was investigated, as well as the factors associated with it.

Methods

The Gambia's Multiple Indicators Cluster Survey (MICS) was used to evaluate the 2018 results. Data was obtained from 3790 women aged 15 to 49 who had also given birth. The univariate analysis was conducted using percentage. The adjusted odds ratios (AOR) were determined using a multivariable logistic regression model (with corresponding 95% confidence interval (CI)). The degree of statistical significance was set at 5%.

Results

Approximately 25.3% (95% CI: 23.1%-27.6%) of the women reported unplanned pregnancy. Women aged 30–34 years had 45% reduction in unplanned pregnancy, when compared with those aged 15–19 years (AOR = 0.55; 95% CI: 0.32–0.94). The Fula and non-Gambian women had 30% and 45% reduction in unplanned pregnancy respectively, when compared with Mandinka women. Those who had no functional difficulties had 47% reduction in unplanned pregnancy, when compared with women who had functional difficulties (AOR = 0.53; 95% CI: 0.30, 0.91). Respondents who had given births to 3–4 and 5 + children were 1.79 and 3.02 times as likely to have unplanned pregnancy, when compared with women who had given birth to 1–2 children. Single/unmarried women were 11.38 times as likely to have unplanned pregnancy, when compared with women currently married/in union (AOR = 11.38; 95% CI: 6.38, 20.29). Local Government Area of residence was significantly associated with unplanned pregnancy. Furthermore, women who were neither happy nor unhappy and 18 + at sexual debut were 1.39 and 1.34 times as likely to have unplanned pregnancy, when compared with the very happy women and those < 18 at sexual debut respectively.

Conclusion

The rate of unintended pregnancies was large (25.3%). Several causes have been linked to unplanned pregnancies. These results suggest that further efforts are required to enhance women's sex education, expand access to family planning services, and provide affordable health care to high-risk women in order to minimize unintended pregnancies.
Local detection of microvessels in IDH-wildtype glioblastoma using relative cerebral blood volume: an imaging marker useful for astrocytoma grade 4 classification
Authors: Álvarez-Torres María del Mar , Fuster-García Elies , Juan-Albarracín Javier , Reynés Gaspar , Aparici-Robles Fernando , Ferrer-Lozano Jaime , García-Gómez Juan Miguel
Published: January 2022

Background

The microvessels area (MVA), derived from microvascular proliferation, is a biomarker useful for high-grade glioma classification. Nevertheless, its measurement is costly, labor-intense, and invasive. Finding radiologic correlations with MVA could provide a complementary non-invasive approach without an extra cost and labor intensity and from the first stage. This study aims to correlate imaging markers, such as relative cerebral blood volume (rCBV), and local MVA in IDH-wildtype glioblastoma, and to propose this imaging marker as useful for astrocytoma grade 4 classification.

Methods

Data from 73 tissue blocks belonging to 17 IDH-wildtype glioblastomas and 7 blocks from 2 IDH-mutant astrocytomas were compiled from the Ivy GAP database. MRI processing and rCBV quantification were carried out using ONCOhabitats methodology. Histologic and MRI co-registration was done manually with experts’ supervision, achieving an accuracy of 88.8% of overlay. Spearman’s correlation was used to analyze the association between rCBV and microvessel area. Mann-Whitney test was used to study differences of rCBV between blocks with presence or absence of microvessels in IDH-wildtype glioblastoma, as well as to find differences with IDH-mutant astrocytoma samples.

Results

Significant positive correlations were found between rCBV and microvessel area in the IDH-wildtype blocks (p < 0.001), as well as significant differences in rCBV were found between blocks with microvascular proliferation and blocks without it (p < 0.0001). In addition, significant differences in rCBV were found between IDH-wildtype glioblastoma and IDH-mutant astrocytoma samples, being 2–2.5 times higher rCBV values in IDH-wildtype glioblastoma samples.

Conclusions

The proposed rCBV marker, calculated from diagnostic MRIs, can detect in IDH-wildtype glioblastoma those regions with microvessels from those without it, and it is significantly correlated with local microvessels area. In addition, the proposed rCBV marker can differentiate the IDH mutation status, providing a complementary non-invasive method for high-grade glioma classification.
Study protocol for reducing disparity in receipt of mother’s own milk in very low birth weight infants (ReDiMOM): a randomized trial to improve adherence to sustained maternal breast pump use
Authors: Johnson Tricia J. , Meier Paula P. , Schoeny Michael E. , Bucek Amelia , Janes Judy E. , Kwiek Jesse J. , Zupancic John A. F. , Keim Sarah A. , Patel Aloka L.
Published: January 2022

Background

Black very low birth weight (VLBW; < 1500 g birth weight) and very preterm (VP, < 32 weeks gestational age, inclusive of extremely preterm, < 28 weeks gestational age) infants are significantly less likely than other VLBW and VP infants to receive mother’s own milk (MOM) through to discharge from the neonatal intensive care unit (NICU). The costs associated with adhering to pumping maternal breast milk are borne by mothers and contribute to this disparity. This randomized controlled trial tests the effectiveness and cost-effectiveness of an intervention to offset maternal costs associated with pumping.

Methods

This randomized control trial will enroll 284 mothers and their VP infants to test an intervention (NICU acquires MOM) developed to facilitate maternal adherence to breast pump use by offsetting maternal costs that serve as barriers to sustaining MOM feedings and the receipt of MOM at NICU discharge. Compared to current standard of care (mother provides MOM), the intervention bundle includes three components: a) free hospital-grade electric breast pump, b) pickup of MOM, and c) payment for opportunity costs. The primary outcome is infant receipt of MOM at the time of NICU discharge, and secondary outcomes include infant receipt of any MOM during the NICU hospitalization, duration of MOM feedings (days), and cumulative dose of MOM feedings (total mL/kg of MOM) received by the infant during the NICU hospitalization; maternal duration of MOM pumping (days) and volume of MOM pumped (mLs); and total cost of NICU care. Additionally, we will compare the cost of the NICU acquiring MOM versus NICU acquiring donor human milk if MOM is not available and the cost-effectiveness of the intervention (NICU acquires MOM) versus standard of care (mother provides MOM).

Discussion

This trial will determine the effectiveness of an economic intervention that transfers the costs of feeding VLBWand VP infants from mothers to the NICU to address the disparity in the receipt of MOM feedings at NICU discharge by Black infants. The cost-effectiveness analysis will provide data that inform the adoption and scalability of this intervention.

Trial registration

ClinicalTrials.gov: NCT04540575, registered September 7, 2020.
Factors influencing medication adherence among patients with severe mental disorders from the perspective of mental health professionals
Authors: Deng Mengjie , Zhai Shuyi , Ouyang Xuan , Liu Zhening , Ross Brendan
Published: January 2022

Background

Medication adherence is a common issue influenced by various factors among patients with severe mental disorders worldwide. However, most literature to date has been primarily quantitative and has focused on medication adherence issue from the perspective of patients or their caregivers. Moreover, research focused on medication adherence issue in China is scarce. Present study aims to explore the influential factors of medication adherence among patients with severe mental disorders form the perspective of mental health professionals in Hunan Province, China.

Methods

A qualitative study was performed in Hunan Province, China with 31 mental health professionals recruited from October to November 2017. And semi-structured interviews or focus group interviews were conducted along with audio recordings of all interviews. Interview transcripts were then coded and analyzed in Nvivo software with standard qualitative approaches.

Results

Three major themes influencing medication adherence among patients with severe mental disorders were identified as: (1) attitudes towards mental disorder/treatment; (2) inadequate aftercare; (3) resource shortages.

Conclusions

This qualitative study identified the factors influencing medication adherence among patients with severe mental disorders in China. As a locally driven research study, it provides practical advice on medication adherence promotion for mental health workers and suggests culturally tailored models that improve the management of patients with severe mental disorders in order to reduce economic burden on individual and societal level.
All are equal, but some are more equal than others: social determinants of leisure time physical activity through the lens of intersectionality
Authors: Mielke Gregore I. , Malta Deborah C. , Nunes Bruno P. , Cairney John
Published: January 2022

Background

To date, no research has investigated social determinants of leisure time physical activity through the lens of intersectionality in a low- and middle-income country. Therefore, the aim of this study was to explore the intersectionality in leisure time physical activity in a nationwide sample of Brazilian adults.

Methods

Data from the Brazilian National Health Survey conducted in 2013 were analysed (N = 58,429). Prevalence of sufficient leisure time physical activity (150+ minutes per week in moderate-to-vigorous physical activity) was estimated according to gender, racial identity, education and income, and according to multiple combinations of these sociodemographic characteristics (i.e., multiple jeopardy index).

Results

The prevalence of sufficient leisure time physical activity was 22.9% (95%CI: 22.3 to 23.6). Overall, the prevalence of sufficient leisure time physical activity was highest among men, individuals with white skin colour, and among those in the highest group of education and income. Among men, white, with a university degree and in the highest quartile of income (3% of the population), the prevalence of sufficient leisure time physical activity was 48%. Among non-white women with low education and low income (8.1% of the population), the prevalence of sufficient leisure time physical activity was 9.8%.

Conclusion

Informed by the theory of intersectionality, findings of this study have shown that intersections of gender, racial identity and socioeconomic position of the Brazilian society strongly influence leisure time physical activity at the individual level. Targeted interventions to increase leisure time physical activity should address the complexities of social status intersections.
Investigating the disjoint between education and health policy for infant feeding among teenage mothers in South Africa: a case for intersectoral work
Authors: Hunter-Adams Jo , Strebel Anna , Corrigall Joanne , Zweigenthal Virginia
Published: January 2022

Background

Many low-and-middle-income countries, including South Africa, have high rates of teenage pregnancy. Following the World Health Organisation recommendations, South African health policy on infant feeding promotes exclusive breastfeeding until six months of age, with gradual weaning. At the same time, South Africa’s education department, in the interest of learners, promotes adolescents’ early return to school post-partum. Yet infant feeding at school is currently not perceived as a realistic option.

Methods

Recognising his this policy tension, we aimed to explore how policies are interpreted and implemented by the health and education sectors through interviews with key informants who produce, interpret and implement these policies. Using an interview guide developed for this study, we conducted in-depth interviews with 24 health policy makers, managers in both sectors, school principals and nursing staff who manage adolescent mothers (aged 16-19) and their babies. Data was analysed using thematic analysis.

Results

Informants from both sectors expressed discomfort at pregnant learners remaining in school late in pregnancy and were uncertain about policy regarding when to return to school and how long to breast-feed. Educators reported that new mothers typically returned to school within a fortnight after delivery and that breastfeeding was not common. While health professionals highlighted the benefits of extended breastfeeding for infants and mothers, they recognised the potential conflict between the need for the mother to return to school and the recommendation for longer breastfeeding. Additionally, the need for ongoing support of young mothers and their families was highlighted.

Conclusions

Our findings suggest educators should actively encourage school attendance in a healthy pregnant adolescent until delivery with later return to school, and health providers should focus attention on breastfeeding for the initial 4-6 weeks postpartum, followed by guided support of formula-feeding. We encourage the active engagement of adolescents’ mothers and extended families who are often involved in infant feeding and care decisions. Education and health departments must engage to facilitate the interests of both the mother and infant: some exclusive infant feeding together with a supported return to school for the adolescent mother.
Obesity as a mortality risk factor in the medical ward: a case control study
Authors: Soffer Shelly , Zimlichman Eyal , Glicksberg Benjamin S. , Efros Orly , Levin Matthew A. , Freeman Robert , Reich David L. , Klang Eyal
Published: January 2022

Background

Research regarding the association between severe obesity and in-hospital mortality is inconsistent. We evaluated the impact of body mass index (BMI) levels on mortality in the medical wards. The analysis was performed separately before and during the COVID-19 pandemic.

Methods

We retrospectively retrieved data of adult patients admitted to the medical wards at the Mount Sinai Health System in New York City. The study was conducted between January 1, 2011, to March 23, 2021. Patients were divided into two sub-cohorts: pre-COVID-19 and during-COVID-19. Patients were then clustered into groups based on BMI ranges. A multivariate logistic regression analysis compared the mortality rate among the BMI groups, before and during the pandemic.

Results

Overall, 179,288 patients were admitted to the medical wards and had a recorded BMI measurement. 149,098 were admitted before the COVID-19 pandemic and 30,190 during the pandemic. Pre-pandemic, multivariate analysis showed a “J curve” between BMI and mortality. Severe obesity (BMI > 40) had an aOR of 0.8 (95% CI:0.7–1.0,p = 0.018) compared to the normal BMI group. In contrast, during the pandemic, the analysis showed a “U curve” between BMI and mortality. Severe obesity had an aOR of 1.7 (95% CI:1.3–2.4,p < 0.001) compared to the normal BMI group.

Conclusions

Medical ward patients with severe obesity have a lower risk for mortality compared to patients with normal BMI. However, this does not apply during COVID-19, where obesity was a leading risk factor for mortality in the medical wards. It is important for the internal medicine physician to understand the intricacies of the association between obesity and medical ward mortality.
A phenomenological study on barriers of adherence to medical advice among type 2 diabetic patients
Authors: Davoodi Monire , Dindamal Behnaz , Dargahi Hossein , Faraji-Khiavi Farzad
Published: January 2022

Background

More than three decades of research and study for overcoming the problem of “non-acceptance/non-compliance” of patients has neither resolved nor reduced the severity of this problem. This phenomenological study aimed to identify barriers of adherence to medical advice among type 2 diabetic patients.

Methods

This study was a qualitative research using phenomenology approach, and the data were analyzed using content analysis approach. Participants were 69 type 2 diabetic patients covered by the diabetes unit of West and East Community Health Centers of Ahvaz, Iran. The views and attitudes of patients about the barriers of adherence to medical advice were elicited by conducting 20–45 min sessions of semi-structured interviews. Data analysis was performed following Colaizzi’s seven-step method.

Results

Barriers of adherence to medical advice were classified into systemic and individual barriers. Individual barriers included 11 codes and 5 categories, and systemic barriers contained within 5 codes and 3 categories. Physiologic and physical factors, financial problems, occupational factors, attitudinal problems and lack of knowledge, and social and family problems were identified as individual barriers. Systemic barriers included inadequate publicizing and limited notification, inadequate equipment and facilities, and poor inter-sectional coordination.

Conclusions

Generally, problems stated by diabetic patients at the individual level can partly be solved by training patients and the people around them. However, as for the systemic problems, it seems that solving the barriers of adherence to medical advice requires coordination with other organizations as well as intersection coordination. Overall, these problems require not only comprehensive health service efforts, but also the support of policymakers to resolve barriers at infrastructure level.
Evaluation of the antidiarrheal activity of 80% methanol extract and solvent fractions of the leaf of Bersama abyssinica fresen (Melianthaceae) in mice
Authors: Ayalew Mihret , Bekele Azmeraw , Mengistie Mestayet Geta , Atnafie Seyfe Asrade
Published: January 2022

Introduction

The use of traditional medicinal plants in the management of diarrhea has long been practiced in Ethiopia.B. abyssinicafresen is one of the plants traditionally used to treat diarrhea whereas an in vivo study had not yet been conducted. Thus, this study aimed to evaluate the antidiarrheal activity of crude extract and solvent fractions of the leaf ofB. abyssinicain mice.

Methods

Cold maceration within 80% methanol was used to extract the leaf powder and extract of the leaf was fractionated using n-hexane, chloroform, and distilled water. The in vivo antidiarrheal activity of crude extracts and solvent fractions were tested in experimental models of castor oil-induced diarrhea, enteropooling, and antimotility test. Five groups each with 6 mice were used under the three antidiarrheal models. Positive controls were treated with loperamide 3 mg/kg and atropine 5 mg/kg and 2% tween 80 was used in the treatment of negative controls. The extract and solvent fractions were administered at doses of 100, 200, and 400 mg/kg. Time of onset of diarrhea, number and weight of total and wet feces, the percent reduction in the number of wet feces, weight and volume of intestinal contents, and percent inhibition of intestinal motility were recorded. Data were analyzed using SPSS version 20.

Result

Defecation of castor oil-induced diarrheal or loose stools was inhibited (p < 0.01 top < 0.001) at 200 mg/kg and 400 mg/kg of crude extract and aqueous fraction. The crude extract and the aqueous fraction at three doses (p < 0.01 top < 0.001), the chloroform fraction at 200 mg/kg and 400 mg/kg (p < 0.01 top < 0.001), and the n-hexane fraction at 400 mg/kg (p < 0.05) reduced intraluminal fluid accumulation compared with the negative control. Castor oil-induced intestinal motility was significantly suppressed with the three-doses of aqueous fraction (p < 0.05 top < 0.001), 200 mg/kg and 400 mg/kg of crude extract (p < 0.05 top < 0.01), 400 mg/kg of chloroform and n-hexane (p < 0.01 top < 0.001) compared with negative control.

Conclusion

The crude extract, aqueous, and chloroform fractions ofB. abyyssinicaleaves have promising anti-diarrheal effects, supporting the plant's traditional use to treat diarrhea.
CRISPR/Cas9-mediated gene knockout and interallelic gene conversion in human induced pluripotent stem cells using non-integrative bacteriophage-chimeric retrovirus-like particles
Authors: Mianné Joffrey , Nasri Amel , Van Chloé Nguyen , Bourguignon Chloé , Fieldès Mathieu , Ahmed Engi , Duthoit Christine , Martin Nicolas , Parrinello Hugues , Louis Anaïs , Iché Alexandra , Gayon Régis , Samain Florine , Lamouroux Lucille , Bouillé Pascale , Bourdin Arnaud , Assou Said , De Vos John
Published: January 2022

Background

The application of CRISPR/Cas9 technology in human induced pluripotent stem cells (hiPSC) holds tremendous potential for basic research and cell-based gene therapy. However, the fulfillment of these promises relies on the capacity to efficiently deliver exogenous nucleic acids and harness the repair mechanisms induced by the nuclease activity in order to knock-out or repair targeted genes. Moreover, transient delivery should be preferred to avoid persistent nuclease activity and to decrease the risk of off-target events. We recently developed bacteriophage-chimeric retrovirus-like particles that exploit the properties of bacteriophage coat proteins to package exogenous RNA, and the benefits of lentiviral transduction to achieve highly efficient, non-integrative RNA delivery in human cells. Here, we investigated the potential of bacteriophage-chimeric retrovirus-like particles for the non-integrative delivery of RNA molecules in hiPSC for CRISPR/Cas9 applications.

Results

We found that these particles efficiently convey RNA molecules for transient expression in hiPSC, with minimal toxicity and without affecting the cell pluripotency and subsequent differentiation. We then used this system to transiently deliver in a single step the CRISPR-Cas9 components (Cas9 mRNA and sgRNA) to generate gene knockout with high indel rate (up to 85%) at multiple loci. Strikingly, when using an allele-specific sgRNA at a locus harboring compound heterozygous mutations, the targeted allele was not altered by NHEJ/MMEJ, but was repaired at high frequency using the homologous wild type allele, i.e., by interallelic gene conversion.

Conclusions

Our results highlight the potential of bacteriophage-chimeric retrovirus-like particles to efficiently and safely deliver RNA molecules in hiPSC, and describe for the first time genome engineering by gene conversion in hiPSC. Harnessing this DNA repair mechanism could facilitate the therapeutic correction of human genetic disorders in hiPSC.
Resveratrol and lycium barbarum polysaccharide improve Qinling giant panda (Ailuropoda melanoleuca Qinlingensis) sperm quality during cryopreservation
Authors: Zhang Ruixue , Dong Hemeng , Zhao Pengpeng , Shang Chunmei , Qi Hang , Ma Yongjie , Gao Chuxi , Zhang Danhui , Shen Jiena , Lei Yinghu , Jin Yaping , Lin Pengfei
Published: January 2022

Background

Semen cryopreservation has become an essential tool for conservation efforts of the giant panda (Ailuropoda melanoleuca); however, it is severely detrimental to sperm quality. Evidence has shown that antioxidants have the potential to reverse cryopreservation-induced damage in sperm. The purpose of this study was to screen effective antioxidants that could retain sperm quality during cryopreservation and to determine the optimal dose. Seven antioxidant groups, including resveratrol (RSV = 50 μM, RSV = 100 μM, RSV = 150 μM), lycium barbarum polysaccharide (LBP = 2 mg/mL, LBP = 4 mg/mL), laminaria japonica polysaccharides (LJP = 1 mg/mL) or combination (LBP = 2 mg/mL, LJP = 1 mg/mL and RSV = 100 μM) were assessed.

Results

RSV, LBP, LJP, or a combination of RSV, LBP, and LJP added to the freezing medium significantly improved sperm progressive motility, plasma membrane integrity, acrosome integrity, and mitochondrial activity during the cryopreservation process. Furthermore, the activities of glutathione peroxidase and superoxide dismutase were also improved. The levels of reactive oxygen species and malondialdehyde in semen were notably reduced. Hyaluronidase activity and acrosin activity were significantly increased in LBP-treated sperm. However, sperm total motility and DNA integrity were not significantly different between the groups.

Conclusions

RSV (50 μM) or LBP (2 mg/mL) are the best candidate antioxidants for inclusion in the freezing medium to improve the quality of giant panda spermatozoa during semen cryopreservation.
Persistent hypercobalaminemia three months after successful gradual attenuation of extrahepatic shunts in dogs: a prospective cohort study
Authors: Devriendt Nausikaa , Serrano Gonçalo , Paepe Dominique , Vandenabeele Sophie , Stock Emmelie , de Rooster Hilde
Published: January 2022

Background

Deficiencies in vitamin A and D and disorders in the vitamin B complex are often present in people with chronic liver diseases. So far, the serum concentrations of these vitamins have not yet been studied in dogs with congenital extrahepatic portosystemic shunts (EHPSS), who also have some degree of liver dysfunction. The objective was to assess serum vitamin concentrations in dogs with EHPSS from diagnosis to complete closure. A prospective cohort study was performed using ten client-owned dogs with EHPSS, closed after gradual surgical attenuation. Serum concentrations of vitamin A, 25-hydroxyvitamin D, folic acid, cobalamin and methylmalonic acid (MMA) were measured at diagnosis prior to institution of medical therapy, prior to surgery, and three months after gradual attenuation and complete closure of the EHPSS.

Results

At diagnosis, median serum concentrations of vitamin A, 25-hydroxyvitamin D and folic acid were 18.2 μg/dL (8.8 - 79.5 μg/dL), 51.8 ng/mL (19.4 - 109.0 ng/mL), and 8.1 μg/L (5.2 - 14.5 μg/L), respectively, which increased significantly postoperatively (88.3 μg/dL (51.6 - 182.2 μg/dL, P=0.005), 89.6 ng/mL (49.3 - >150.0 ng/mL, P =0.005), and 14.8 μg/L (11.5 - 17.7 μg/L, P <0.001), respectively). Median serum cobalamin concentrations were 735.5 ng/L (470 - 1388 ng/L) at diagnosis and did not significantly decrease postoperatively (P =0.122). Both at diagnosis and three months postoperatively 7/10 dogs had hypercobalaminemia.

Conclusions

Serum concentrations of vitamin A, 25-hydroxyvitamin D and folic acid significantly increase after surgical attenuation. Nevertheless, persistent hypercobalaminemia is suggestive of ongoing liver dysfunction, despite successful surgery.
Clinicopathological investigation of secretory carcinoma cases including a successful treatment outcome using entrectinib for high-grade transformation: a case report
Authors: Suzuki Kensuke , Harada Hiroshi , Takeda Masayuki , Ohe Chisato , Uemura Yoshiko , Kawahara Akihiko , Sawada Shunsuke , Kanda Akira , Sengupta Bhaswati , Iwai Hiroshi
Published: January 2022

Background

Secretory carcinoma (SC) of the salivary gland is a recently described malignant tumor harboring characteristic ETV6-NTRK3 gene fusion. SC generally has a favorable clinical course, and is currently regarded as a low-grade carcinoma. However, a small subset of SCs demonstrates aggressive clinical features with histologically high-grade transformed morphology, the molecular pathogenesis of which has not yet been elucidated. In this study, we performed a clinicopathological and molecular genetic study of patients with SC of the head and neck displaying various clinical characteristics to investigate the differences of pathological and molecular genetics between low-grade and high-grade components of SC.

Case presentation

Three cases with SC of the head and neck, including a conventional low-grade SC and two high-grade transformed SCs are described. High-grade transformed SCs with histological features such as nuclear polymorphism, distinctive nucleoli and increased mitotic activity developed locoregional recurrence and distant metastasis. Immunohistochemical analysis revealed that low- and high-grade components showed different expression patterns for S-100 protein and mammaglobin, whereas all examined components were positive for p-STAT5. p53-positive cell population was markedly higher in one case with high-grade transformed SC. The proliferative activity of high-grade components was markedly increased, with the Ki-67 labeling index ranging up to 30–32%. A fluorescence in situ hybridization study with an ETV6 (12p13) break apart probe revealed split signals in the nuclei in all 3 cases. A targeted next-generation sequencing-based fusion assay demonstrated that all 6 clinical samples from the 3 patients showed the presence of the ETV6-NTRK3 fusion transcripts. One patient with high-grade transformed SC showed a dramatic clinical response to the pan-TRK inhibitor, entrectinib, for the treatment of locoregional recurrence and pulmonary metastasis.

Conclusions

High-grade transformed SC showed aggressive clinical and pathological features with increased Ki-67 labeling index. Molecular genetic study of gene rearrangement appears to be beneficial treatment as the presence of ETV6-NTRK3 translocation may represent a therapeutic target in SC, particularly the high-grade transformed type.
Risk factors for the accuracy of the initial diagnosis of malaria cases in China: a decision-tree modelling approach
Authors: Li Gang , Zhang Donglan , Chen Zhuo , Feng Da , Cai Xinyan , Chen Xiaoyu , Tang Shangfeng , Feng Zhanchun
Published: January 2022

Background

Early accurate diagnosis and risk assessment for malaria are crucial for improving patients’ terminal prognosis and preventing them from progressing to a severe or critical stage. This study aims to describe the accuracy of the initial diagnosis of malaria cases with different characteristics and the factors that affect the accuracy in the context of the agenda for a world free of malaria.

Methods

A retrospective study was conducted on 494 patients admitted to hospitals with a diagnosis of malaria from January 2014 through December 2016. Descriptive statistics were calculated, and decision tree analysis was performed to predict the probability of patients who may be misdiagnosed.

Results

Of the 494 patients included in this study, the proportions of patients seeking care in county-level, prefecture-level and provincial-level hospitals were 27.5% (n = 136), 26.3% (n = 130) and 8.3% (n = 41), respectively; the proportions of patients seeking care in clinic, township health centre and Centres for Disease Control and Prevention were 25.9% (n = 128), 4.1% (n = 20), and 7.9% (n = 39), respectively. Nearly 60% of malaria patients were misdiagnosed on their first visit, and 18.8% had complications. The median time from onset to the first visit was 2 days (IQR: 0-3 days), and the median time from the first visit to diagnosis was 3 days (IQR: 0–4 days). The decision tree classification of malaria patients being misdiagnosed consisted of six categorical variables: healthcare facilities for the initial diagnosis, time interval between onset and initial diagnosis, region, residence type, insurance status, and age.

Conclusions

Insufficient diagnostic capacity of healthcare facilities with lower administrative levels for the first visit was the most important risk factor in misdiagnosing patients. To reduce diagnostic errors, clinicians, government decision-makers and communities should consider strengthening the primary care facilities, the time interval between onset and initial diagnosis, residence type, and health insurance status.
Impact of nutritional status on heart failure mortality: a retrospective cohort study
Authors: Abdoul Carime Nafiz , Cottenet Jonathan , Clerfond Guillaume , Eschalier Romain , Quilliot Didier , Eicher Jean-Christophe , Joly Bertrand , Quantin Catherine
Published: January 2022

Background

Chronic heart failure (CHF) is one of the most common causes of mortality in industrialized countries despite regular therapeutic advances. Numerous factors influence mortality in CHF patients, including nutritional status. It is known that malnutrition is a risk factor for mortality, whereas obesity may play a protective role, a phenomenon dubbed the “obesity paradox”. However, the effect of the obesity-malnutrition association on mortality has not been previously studied for CHF. Our aim was to study the effect of nutritional status on overall mortality in CHF patients.

Methods

This retrospective, multicenter study was based on a French nationwide database (PMSI). We included all CHF patients aged ≥18 years admitted to all public and private hospitals between 2012 and 2016 and performed a survival analysis over 1 to 4 years of follow-up.

Results

Malnutrition led to a significant decrease in life expectancy in CHF patients when compared with normal nutritional status (aHR=1.16 [1.14-1.18] at one year and aHR=1.04 [1.004-1.08] at four years), obese, and obese-malnutrition groups. In contrast, obesity led to a significant increase in life expectancy compared with normal nutritional status (aHR=0.75 [0.73-0.78] at one year and aHR=0.85 [0.81-0.90] at four years), malnutrition, and obese-malnutrition groups. The mortality rate was similar in patients presenting both malnutrition and obesity and patients with normal nutritional status.

Conclusions

Our results indicate that the protective effect on mortality observed in obese CHF patients seems to be linked to fat massincrease. Furthermore, malnourished obese and normal nutritional status patients had similar mortality rates. Further studies should be conducted to confirm our results and to explore the physiopathological mechanisms behind these effects.
New approach for genomic characterisation of equine sarcoid-derived BPV-1/-2 using nanopore-based sequencing
Authors: Gysens Lien , Vanmechelen Bert , Haspeslagh Maarten , Maes Piet , Martens Ann
Published: January 2022

Background

Bovine papillomavirus (BPV) types 1 and 2 play a central role in the etiology of the most common neoplasm in horses, the equine sarcoid. The unknown mechanism behind the unique variety in clinical presentation on the one hand and the host dependent clinical outcome of BPV-1 infection on the other hand indicate the involvement of additional factors. Earlier studies have reported the potential functional significance of intratypic sequence variants, along with the existence of sarcoid-sourced BPV variants. Therefore, intratypic sequence variation seems to be an important emerging viral factor. This study aimed to give a broad insight in sarcoid-sourced BPV variation and explore its potential association with disease presentation.

Methods

In order to do this, a nanopore sequencing approach was successfully optimized for screening a wide spectrum of clinical samples. Specimens of each tumour were initially screened for BPV-1/-2 by quantitative real-time PCR. A custom-designed primer set was used on BPV-positive samples to amplify the complete viral genome in two multiplex PCR reactions, resulting in a set of overlapping amplicons. For phylogenetic analysis, separate alignments were made of all available complete genome sequences for BPV-1/-2. The resulting alignments were used to infer Bayesian phylogenetic trees.

Results

We found substantial genetic variation among sarcoid-derived BPV-1, although this variation could not be linked to disease severity. Several of the BPV-1 genomes had multiple major deletions. Remarkably, the majority of them cluster within the region coding for late viral genes. Together with the extensiveness (up to 603 nucleotides) of the described deletions, this suggests an altered function of L1/L2 in disease pathogenesis.

Conclusions

By generating a significant amount of complete-length BPV genomes, we succeeded to introduce next-generation sequencing into veterinary research focusing on the equine sarcoid, thus facilitating the first report of both nanopore-based sequencing of complete sarcoid-sourced BPV-1/-2 and the simultaneous nanopore sequencing of multiple complete genomes originating from a single clinical sample.
Diagnostic accuracy of calprotectin in periprosthetic joint infection: a diagnostic meta-analysis
Authors: Xing Jisi , Li Jiahao , Yan Zijian , Li Yijin , Liu Xiaofang , He Lilei , Xu Ting , Wang Changbing , Zhao Lilian , Jie Ke
Published: January 2022

Background

Periprosthetic joint infection (PJI) is considered to be one of the most challenging complications of joint replacement, which remains unpredictable. As a simple and emerging biomarker, calprotectin (CLP) has been considered to be useful in ruling out PJI in recent years. The purpose of this study was to investigate the accuracy and sensitivity of CLP in the diagnosis of PJI.

Methods

We searched and screened the publications from PubMed, Web of Science, EMBASE, and Cochrane Library from database establishment to June 2021. Subsequently, Stata version 16.0 software was used to combine the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), operating characteristic curve, and area under the curve (AUC). Heterogeneity across articles was evaluated by the I2 statistics. Finally, sources of heterogeneity were detected by subgroup analysis based on study design, detection method, sample size, and cutoff values.

Results

A total of 7 studies were included in our study, comprising 525 patients. The pooled sensitivity, specificity, PLR, and NLR of CLP for PJI diagnosis were 0.94(95% CI 0.87–0.98), 0.93(95% CI 0.87–0.96), 13.65(95% CI 6.89–27.08), and 0.06(95% CI 0.02–0.15), respectively, while the DOR and AUC were 222.33(95% CI 52.52–941.11) and 0.98 (95% CI 0.96–0.99), respectively.

Conclusion

Synovial CLP is a reliable biomarker and can be used as a diagnostic criterion for PJI in the future. However, the uncertainty resulting from the poor study numbers and sample sizes limit our ability to definitely draw conclusions on the basis of our study.
Constitutively active SARM1 variants that induce neuropathy are enriched in ALS patients
Authors: Bloom A. Joseph , Mao Xianrong , Strickland Amy , Sasaki Yo , Milbrandt Jeffrey , DiAntonio Aaron
Published: January 2022

Background

In response to injury, neurons activate a program of organized axon self-destruction initiated by the NAD+ hydrolase, SARM1. In healthy neurons SARM1 is autoinhibited, but single amino acid changes can abolish autoinhibition leading to constitutively active SARM1 enzymes that promote degeneration when expressed in cultured neurons.

Methods

To investigate whether naturally occurring human variants might disrupt SARM1 autoinhibition and potentially contribute to risk for neurodegenerative disease, we assayed the enzymatic activity of all 42 rare SARM1 alleles identified among 8507 amyotrophic lateral sclerosis (ALS) patients and 9671 controls. We then intrathecally injected mice with virus expressing SARM1 constructs to test the capacity of an ALS-associated constitutively active SARM1 variant to promote neurodegeneration in vivo.

Results

Twelve out of 42 SARM1 missense variants or small in-frame deletions assayed exhibit constitutive NADase activity, including more than half of those that are unique to the ALS patients or that occur in multiple patients. There is a > 5-fold enrichment of constitutively active variants among patients compared to controls. Expression of constitutively active ALS-associated SARM1 alleles in cultured dorsal root ganglion (DRG) neurons is pro-degenerative and cytotoxic. Intrathecal injection of an AAV expressing the common SARM1 reference allele is innocuous to mice, but a construct harboring SARM1V184G, the constitutively active variant found most frequently among the ALS patients, causes axon loss, motor dysfunction, and sustained neuroinflammation.

Conclusions

These results implicate rare hypermorphic SARM1 alleles as candidate genetic risk factors for ALS and other neurodegenerative conditions.
Achieving robust somatic mutation detection with deep learning models derived from reference data sets of a cancer sample
Authors: Sahraeian Sayed Mohammad Ebrahim , Fang Li Tai , Karagiannis Konstantinos , Moos Malcolm , Smith Sean , Santana-Quintero Luis , Xiao Chunlin , Colgan Michael , Hong Huixiao , Mohiyuddin Marghoob , Xiao Wenming
Published: January 2022

Background

Accurate detection of somatic mutations is challenging but critical in understanding cancer formation, progression, and treatment. We recently proposed NeuSomatic, the first deep convolutional neural network-based somatic mutation detection approach, and demonstrated performance advantages on in silico data.

Results

In this study, we use the first comprehensive and well-characterized somatic reference data sets from the SEQC2 consortium to investigate best practices for using a deep learning framework in cancer mutation detection. Using the high-confidence somatic mutations established for a cancer cell line by the consortium, we identify the best strategy for building robust models on multiple data sets derived from samples representing real scenarios, for example, a model trained on a combination of real and spike-in mutations had the highest average performance.

Conclusions

The strategy identified in our study achieved high robustness across multiple sequencing technologies for fresh and FFPE DNA input, varying tumor/normal purities, and different coverages, with significant superiority over conventional detection approaches in general, as well as in challenging situations such as low coverage, low variant allele frequency, DNA damage, and difficult genomic regions