bluuebunny/crossref_metadata_2025 huggingface dataset:
Variants associated with Bedaquiline (BDQ) resistance identified in Rv0678 and efflux pump genes in Mycobacterium tuberculosis isolates from BDQ naïve TB patients in Pakistan
Authors: Saeed Dania Khalid , Shakoor Sadia , Razzak Safina Abdul , Hasan Zahra , Sabzwari Saba Faraz , Azizullah Zahida , Kanji Akbar , Nasir Asghar , Shafiq Samreen , Ghanchi Najia Karim , Hasan Rumina
Published: February 2022

Background

Mutations in theRv0678,pepQandatpEgenes ofMycobacterium tuberculosis(MTB) have been reported to be associated with reduced antimycobacterial susceptibility to bedaquiline (BDQ). Resistance conferring mutations in treatment naïve MTB strains is likely to have implications for BDQ based new drug regimen that aim to shorten treatment duration. We therefore investigated the genetic basis of resistance to BDQ in MTB clinical isolates from BDQ naïve TB patients from Pakistan. In addition, mutations in genes associated with efflux pumps were investigated as an alternate mechanism of resistance.

Methods

Based on convenience sampling, we studied 48 MTB clinical isolates from BDQ naïve TB patients. These isolates (from our strain bank) included 38 MDR/pre-XDR/XDR (10 BDQ resistant, 8 BDQ intermediate and 20 BDQ susceptible) and 10 pan drug susceptible MTB isolates. All strains were subjected to whole genome sequencing and genomes were analysed to identify variants inRv0678, pepQ,atpE, Rv1979c, mmpLS and mmpL5and drug resistance associated efflux pump genes.

Results

Of the BDQ resistant and intermediate strains 44% (8/18) had variants inRv0678including; two reported mutations S63R/G, six previously unreported variants; L40F, R50Q and R107C and three frameshift mutations; G25fs, D64fs and D109fs.

Variants in efflux pumps;Rv1273c(G462K),Rv0507c(R426H) andRv1634c(E198R) were found to be present in drug resistant isolates including BDQ resistant and intermediate isolates. E198R in efflux pump geneRv1634cwas the most frequently occurring variant in BDQ resistant and intermediate isolates (n = 10).

Conclusion

We found RAVs inRv0678to be commonly associated with BDQ resistance. Further confirmation of the role of variants in efflux pump genes in resistance is required so that they may be incorporated in genome-based diagnostics for drug resistant MTB.
Complete sputum smear monitoring among adults with pulmonary tuberculosis in central Uganda: evidence from a retrospective cohort study
Authors: Nsubuga Ronald , Adrawa Norbert , Okoboi Stephen , Komuhangi Alimah , Izudi Jonathan
Published: February 2022

Background

People with bacteriologically confirmed pulmonary tuberculosis require sputum smear monitoring at 2, 5, and 6 months to establish treatment outcomes. However, there is limited information about sputum smear monitoring in Uganda, similar to other developing countries. We examined factors associated with complete sputum smear monitoring among persons with bacteriologically confirmed pulmonary TB aged ≥ 15 years in central Uganda.

Methods

We retrospectively reviewed and abstracted data for persons with bacteriologically confirmed pulmonary TB initiated on treatment between January 2017 and December 2019 across 11 large TB units in Masaka district in central Uganda. Complete sputum smear monitoring was measured as the receipt of three sputum smear microscopy tests at 2, 5, and 6 months of TB treatment. The data were summarized descriptively and the differences in the outcome with independent variables were examined using tests of statistical significance, namely the Chi-square or Fisher’s exact test and the student’s t-test. The factors independently associated with the outcome were established using the modified Poisson regression analysis with robust standard errors, reported as adjusted risk ratio (aRR) along with the 95% confidence interval (CI).

Results

A total of 416 participants were enrolled, with a mean age of 37.3 ± 12.9 years. Of the participants, 290 (69.7) were males, 269 (64.7) were rural residents, and 128 (30.8%) had complete sputum smear monitoring. Urban residence (aRR, 1.45; 95% CI 1.12–1.90) and treatment under the community-based directly observed therapy short-course strategy (DOTS) (aRR, 1.91; 95% CI 1.25–2.92) were associated with a higher likelihood of complete sputum smear monitoring while TB and human immunodeficiency virus (TB/HIV) comorbidity (aRR 0.45, 95% CI 0.30–0.68) was associated with a lower likelihood of complete sputum smear monitoring.

Conclusions

We found a low magnitude of complete sputum smear monitoring among persons with bacteriologically confirmed pulmonary TB aged ≥ 15 years in central Uganda. Strategies to enhance the performance of sputum smear monitoring should target rural health facilities, strengthen TB/HIV collaboration and the implementation of community-based DOTS.
Applying reflective multicriteria decision analysis to understand the value of therapeutic alternatives in the management of gestational and peripartum anaemia in Spain
Authors: Casellas Caro Manel , Hidalgo María Jesús Cancelo , García-Erce José Antonio , Baquero Úbeda José Luis , Torras Boatella Maria Glòria , Gredilla Díaz Elena , Ruano Encinar Margarita , Martín Bayón Israel , Nicolás Picó Jordi , Arjona Berral José Eduardo , Muñoz Solano Alberto , Jiménez Merino Silvia , Cerezales Mónica , Cuervo Jesús
Published: February 2022

Background

The objective of the FeminFER project was to assess the value of ferric carboxymaltose following a multicriteria decision analysis in obstetrics and gynaecology in Spain.

Methods

Ferric carboxymaltose (FCM) and ferrous sulphate were evaluated using the EVIDEM framework. Ten stakeholders participated to collect different perspectives. The framework was adapted considering evidence retrieved with a PICO-S search strategy and grey literature. Criteria/subcriteria were weighted by level of relevance and an evidence-based decision-making exercise was developed in each criterion; weights and scores were combined to obtain the value of intervention relative to each criterion/subcriterion, that were further combined into the Modulated Relative Benefit-Risk Balance (MRBRB).

Results

The most important criterion favouring FCM was Compared Efficacy/Effectiveness (0.183 ± 0.07), followed by Patient Preferences (0.059 ± 0.10). Only Direct medical costs criterion favoured FS (-0.003 ± 0.03). MRBRB favoured FCM; 0.45 ± 0.19; in a scale from -1 to + 1.

Conclusions

In conclusion, considering the several criteria involved in the decision-making process, participants agreed with the use of FCM according to its MRBRB.
Patient-centred consent in women’s health: does it really work in antenatal and intra-partum care?
Authors: Nicholls Jacqueline , David Anna L , Iskaros Joseph , Lanceley Anne
Published: February 2022

Background

Legal and social changes mean that information sharing and consent in antenatal and intrapartum settings is contentious, poorly understood and uncertain for healthcare professionals. This study aimed to investigate healthcare professionals’ views and experiences of the consent process in antenatal and intrapartum care.

Methods

Qualitative research performed in a large urban teaching hospital in London. Fifteen healthcare professionals (obstetricians and midwives) participated in semi-structured in-depth interviews. Data were collectively analysed to identify themes in the experiences of the consent process.

Results

Three themes were identified: (1) Shared decision-making and shared responsibility –engaging women in dialogue is often difficult and, even when achieved, women are not always able or do not wish to share responsibility for decisions (2) Second-guessing women – assessing what is important to a woman is inherently difficult so healthcare professionals sometimes feel forced to anticipate a woman’s views (3) Challenging professional contexts – healthcare professionals are disquieted by consent practice in the Labour ward setting which is often at odds with legal and professional guidance.

Conclusions

Results suggest that there is a mismatch between what is required of healthcare professionals to effect an antenatal or intrapartum consent process concordant with current legal and professional guidance and what can be achieved in practice. If consent, as currently articulated, is to remain the barometer for current practice, healthcare professionals need more support in ways of enabling women to make decisions which healthcare professionals feel confident are autonomous whatever the circumstances of the consultation.
Prevalence of specific and recurrent/founder pathogenic variants in BRCA genes in breast and ovarian cancer in North Africa
Authors: ElBiad Oubaida , Laraqui Abdelilah , El Boukhrissi Fatima , Mounjid Chaimaa , Lamsisi Maryame , Bajjou Tahar , Elannaz Hicham , Lahlou Amine Idriss , Kouach Jaouad , Benchekroune Khadija , Oukabli Mohammed , Chahdi Hafsa , Ennaji Moulay Mustapha , Tanz Rachid , Sbitti Yassir , Ichou Mohammed , Ennibi Khalid , Badaoui Bouabid , Sekhsokh Yassine
Published: February 2022

Background

Elucidation of specific and recurrent/founder pathogenic variants (PVs) inBRCA(BRCA1andBRCA2) genes can make the genetic testing, for breast cancer (BC) and/or ovarian cancer (OC), affordable for developing nations.

Methods

To establish the knowledge aboutBRCAPVs and to determine the prevalence of the specific and recurrent/founder variants inBRCAgenes in BC and/or OC women in North Africa, a systematic review was conducted in Morocco, Algeria, and Tunisia.

Results

Search of the databases yielded 25 relevant references, including eleven studies in Morocco, five in Algeria, and nine in Tunisia. Overall, 15 studies investigated bothBRCA1andBRCA2genes, four studies examined the entire coding region of theBRCA1gene, and six studies in which the analysis was limited to a fewBRCA1and/orBRCA2exons. Overall, 76 PVs (44 inBRCA1and32 inBRCA2) were identified in 196 BC and/or OC patients (129BRCA1and 67BRCA2carriers). Eighteen of the 76 (23.7%) PVs [10/44 (22.7%) inBRCA1and 8/32 (25%) inBRCA2] were reported for the first time and considered to be novel PVs. Among those identified as unlikely to be of North African origin, theBRCA1c.68_69del andBRCA1c.5266dupC Jewish founder alleles and PVs that have been reported as recurrent/founder variants in European populations (ex:BRCA1c.181T>G,BRCA1c1016dupA). The most well characterized PVs are four inBRCA1gene [c.211dupA (14.7%), c.798_799detTT (14%), c.5266dup (8.5%), c.5309G>T (7.8%), c.3279delC (4.7%)] and one inBRCA2[c.1310_1313detAAGA (38.9%)]. The c.211dupA and c.5309G>T PVs were identified as specific founder variants in Tunisia and Morocco, accounting for 35.2% (19/54) and 20.4% (10/49) of total establishedBRCA1PVs, respectively. c.798_799delTT variant was identified in 14% (18/129) of allBRCA1North African carriers, suggesting a founder allele. A broad spectrum of recurrent variants includingBRCA13279delC,BRCA1c.5266dup andBRCA2c.1310_1313detAAGA was detected in 42 patients.BRCA1founder variants explain around 36.4% (47/129) of BC and outnumberBRCA2founder variants by a ratio of ≈3:1.

Conclusions

Testing BC and/or OC patients for the panel of specific and recurrent/founder PVs might be the most cost-effective molecular diagnosis strategy.
Overweight and obesity in non-pregnant women of childbearing age in South Africa: subgroup regression analyses of survey data from 1998 to 2017
Authors: Nglazi Mweete Debra , Ataguba John Ele-Ojo
Published: February 2022

Background

Overweight and obesity in adults are increasing globally and in South Africa (SA), contributing substantially to deaths and disability from non-communicable diseases. Compared to men, women suffer a disproportionate burden of obesity, which adversely affects their health and that of their offspring. This study assessed the changing patterns in prevalence and determinants of overweight and obesity among non-pregnant women in SA aged 15 to 49 years (women of childbearing age (WCBA)) between 1998 and 2017.

Methods

This paper conducts secondary data analysis of seven consecutive nationally representative household surveys—the 1998 and 2016 SA Demographic and Health Surveys, 2008, 2010–2011, 2012, 2014–2015 and 2017 waves of the National Income Dynamics Survey, containing anthropometric and sociodemographic data. The changing patterns of the overweight and obesity prevalence were assessed across key variables. The inferential assessment was based on a standard t-test for the prevalence. Adjusted odds ratios from logistic regression analysis were used to examine the factors associated with overweight and obesity at each time point.

Results

Overweight and obesity prevalence among WCBA in SA increased from 51.3 to 60.0% and 24.7 to 35.2%, respectively, between 1998 and 2017. The urban-rural disparities in overweight and obesity decreased steadily between 1998 and 2017. The prevalence of overweight and obesity among WCBA varied by age, population group, location, current smoking status and socioeconomic status of women. For most women, the prevalence of overweight and/or obesity in 2017 was significantly higher than in 1998. Significant factors associated with being overweight and obese included increased age, self-identifying with the Black African population group, higher educational attainment, urban area residence, and wealthier socioeconomic quintiles. Smoking was inversely related to being overweight and obese.

Conclusions

The increasing trend in overweight and obesity in WCBA in SA demands urgent public health attention. Increased public awareness is needed about obesity and its health consequences for this vulnerable population. Efforts are needed across different sectors to prevent excessive weight gain in WCBA, focusing on older women, self-identified Black African population group, women with higher educational attainment, women residing in urban areas, and wealthy women.
An exploration of pregnant women and mothers’ attitudes, perceptions and experiences of formula feeding and formula marketing, and the factors that influence decision-making about infant feeding in South Africa
Authors: Horwood Christiane , Luthuli Silondile , Pereira-Kotze Catherine , Haskins Lyn , Kingston Gillian , Dlamini-Nqeketo Sithembile , Tshitaudzi Gilbert , Doherty Tanya
Published: February 2022

Background

Despite strong evidence showing the lifelong benefits of breastfeeding for mothers and children, global breastfeeding practices remain poor. The International Code of Marketing of Breastmilk Substitutes is an internationally agreed code of practice, adopted by the World Health Assembly in 1981, to regulate promotion of commercial formula, and is supported by legislation in many countries. However, marketing of formula remains widespread and contributes to mother’s decisions to formula feed. We present South African data from a multi-country, mixed-methods study exploring women’s decision-making about infant feeding and how this was influenced by exposure to formula marketing.

Methods

Using a consumer-based marketing approach, focus group discussions (FGDs) were conducted with pregnant women and mothers of children aged between 0 and 18 months in two urban sites in South Africa. Participants were purposively selected according to their child’s age, infant feeding practices and socioeconomic status. Ten FGDs were conducted during February 2020 with a total of 69 participants. Thematic analysis was used to analyse the data with NVivo v.12 software.

Results

Despite being encouraged by health professionals to breastfeed and intending to do so, many mothers chose to give formula in the early weeks and months of their child’s life. Mothers reported breastfeeding challenges as the most frequent reason for initiating infant formula, stating that family members and health professionals recommended formula to solve these challenges. Although participants described few advertisements for infant formula, advertisements for ‘growing-up’ formulas for older children were widespread and promoted brand recognition. Mothers experienced other marketing approaches including attractive packaging and shop displays of infant formula, and obtained information from social media and online mothers’ groups, which influenced their choice of formula brand. Mothers reported strong brand loyalty derived from previous experiences and recommendations. Health professionals frequently recommended formula, including recommending specific formula brands and specialist formulas.

Conclusion

Global formula companies use multifaceted marketing methods to promote a strong narrative portraying formula feeding as a positive lifestyle choice. Positive, coordinated efforts are required to counter pro-formula messaging and change the narrative to support breastfeeding as an aspirational choice. In particular, health professionals must stop supporting the formula industry.
Association of variants m.T16172C and m.T16519C in whole mtDNA sequences with high altitude pulmonary edema in Han Chinese lowlanders
Authors: Wang Yan , Huang Xuewen , Peng Fujun , Han Huiling , Gu Yanan , Liu Xin , Feng Zhichun
Published: February 2022

Background

High altitude pulmonary edema (HAPE) is a hypoxia-induced non-cardiogenic pulmonary edema that typically occurred in un-acclimatized lowlanders, which inevitably leads to life-threatening consequences. Apart from multiple factors involved, the genetic factors also play an important role in the pathogenesis of HAPE. So far, researchers have put more energy into the nuclear genome and HAPE, and ignored the relationship between the mitochondrion DNA (mtDNA) variants and HAPE susceptibility.

Methods

We recruited a total of 366 individuals including 181 HAPE patients and 185 non-HAPE populations through two times. The first time, 49 HAPE patients and 58 non-HAPE individuals were performed through whole mtDNA sequences to search the mutations and haplogroups. The second time, 132 HAPE patients and 127 non-HAPE subjects were collected to apply verifying these mutations and haplogroups of mtDNA with the routine PCR method.

Results

We analyzed and summarized the clinical characteristics and sequence data for the 49 HAPE patients and 58 non-HAPE individuals. We found that a series of routine blood indexes including systolic arterial blood pressure (SBP), heart rate (HR), white blood cell (WBC), and C-reactive protein (CRP) in the HAPE group presented higher and displayed significant differences compared with those in the non-HAPE group. Although the average numbers of variants in different region and group samples were not statistically significant (P > 0.05), the mutation densities of different regions in the internal group showed significant differences. Then we found two mutations (T16172C and T16519C) associated with the HAPE susceptibility, the T16172C mutation increased the risk of HAPE, and the T16519C mutation decreased the HAPE rating. Furthermore, the two mutations were demonstrated with 132 HAPE patients and 127 non-HAPE individuals. Unfortunately, all the haplogroups were not associated with the HAPE haplogroups.

Conclusions

We provided evidence of differences in mtDNA polymorphism frequencies between HAPE and non-HAPE Han Chinese. Genotypes of mtDNA 16172C and 16519C were correlated with HAPE susceptibility, indicating the role of the mitochondrial genome in the pathogenesis of HAPE.
Cost-effectiveness of artificial intelligence screening for diabetic retinopathy in rural China
Authors: Huang Xiao-Mei , Yang Bo-Fan , Zheng Wen-Lin , Liu Qun , Xiao Fan , Ouyang Pei-Wen , Li Mei-Jun , Li Xiu-Yun , Meng Jing , Zhang Tian-Tian , Cui Yu-Hong , Pan Hong-Wei
Published: February 2022

Background

Diabetic retinopathy (DR) has become a leading cause of global blindness as a microvascular complication of diabetes. Regular screening of diabetic retinopathy is strongly recommended for people with diabetes so that timely treatment can be provided to reduce the incidence of visual impairment. However, DR screening is not well carried out due to lack of eye care facilities, especially in the rural areas of China. Artificial intelligence (AI) based DR screening has emerged as a novel strategy and show promising diagnostic performance in sensitivity and specificity, relieving the pressure of the shortage of facilities and ophthalmologists because of its quick and accurate diagnosis. In this study, we estimated the cost-effectiveness of AI screening for DR in rural China based on Markov model, providing evidence for extending use of AI screening for DR.

Methods

We estimated the cost-effectiveness of AI screening and compared it with ophthalmologist screening in which fundus images are evaluated by ophthalmologists. We developed a Markov model-based hybrid decision tree to analyze the costs, effectiveness and incremental cost-effectiveness ratio (ICER) of AI screening strategies relative to no screening strategies and ophthalmologist screening strategies (dominated) over 35 years (mean life expectancy of diabetes patients in rural China). The analysis was conducted from the health system perspective (included direct medical costs) and societal perspective (included medical and nonmedical costs). Effectiveness was analyzed with quality-adjusted life years (QALYs). The robustness of results was estimated by performing one-way sensitivity analysis and probabilistic analysis.

Results

From the health system perspective, AI screening and ophthalmologist screening had incremental costs of $180.19 and $215.05 but more quality-adjusted life years (QALYs) compared with no screening. AI screening had an ICER of $1,107.63. From the societal perspective which considers all direct and indirect costs, AI screening had an ICER of $10,347.12 compared with no screening, below the cost-effective threshold (1–3 times per capita GDP of Chinese in 2019).

Conclusions

Our analysis demonstrates that AI-based screening is more cost-effective compared with conventional ophthalmologist screening and holds great promise to be an alternative approach for DR screening in the rural area of China.
The impact of kidney function in patients on antithrombotic therapy: a post hoc subgroup analysis focusing on recurrent bleeding events from the AFIRE trial
Authors: Matsui Kunihiko , Yasuda Satoshi , Kaikita Koichi , Akao Masaharu , Ako Junya , Matoba Tetsuya , Nakamura Masato , Miyauchi Katsumi , Hagiwara Nobuhisa , Kimura Kazuo , Hirayama Atsushi , Ogawa Hisao
Published: February 2022

Background

The success of antithrombotic therapies is assessed based on thrombotic and bleeding events. Simultaneously assessing both kinds of events might be challenging, and recurrent bleeding events are often ignored. We tried to confirm the effects of kidney function on outcome events in patients undergoing antithrombotic therapy.

Methods

As a post hoc subgroup analysis of the Atrial Fibrillation and Ischemic Events with Rivaroxaban in Patients with Stable Coronary Artery Disease (AFIRE) trial, a randomized clinical trial with a median follow-up of 36 months, patients were divided into high and low estimated glomerular filtration rate (eGFR) groups with a cutoff value of 50 mL/min. The cumulative incidence of bleeding and crude incidence of recurrent bleeding per 100 patient-years were calculated. We used the Cox regression model with multiple failure time data for recurrent bleeding events.

Results

Among 2092 patients, 1386 (66.3%) showed high eGFR. The cumulative bleeding events per 100 patients at 1 year were 5.4 and 6.2 in the high and low eGFR groups, respectively. The difference continued to increase over time. The hazard ratio for time to the first bleeding event in the high eGFR group was 0.875 (95% confidence interval 0.701–1.090, p = .234) and that for the first composite event was 0.723 (95% confidence interval 0.603–0.867, p < .000). The recurrent bleeding events per 100 person-years were 11.3 and 15.3 in the high and low eGFR groups, respectively, with a rate ratio of 0.738 (95% confidence interval 0.615–0.886, p = .001). During the observation period, the risk of bleeding changed with time. It peaked soon after the study enrollment in both groups. It decreased continuously in the high eGFR group but remained high in the low eGFR group.

Conclusions

We reaffirmed that kidney function affects bleeding events in patients on antithrombotic therapy, considering recurrent events. Patients should have detailed discussions with physicians regarding the possible bleeding events when continuing antithrombotic therapy, especially in patients with decreased kidney function.

Trial registration

UMIN Clinical Trials Registry, UMIN000016612. ClinicalTrials.gov, NCT02642419. Registered on 21 October 2015.
Triglyceride-glucose index trajectory and arterial stiffness: results from Hanzhong Adolescent Hypertension Cohort Study
Authors: Yan Yu , Wang Dan , Sun Yue , Ma Qiong , Wang Keke , Liao Yueyuan , Chen Chen , Jia Hao , Chu Chao , Zheng Wenling , Hu Jiawen , Yuan Yue , Wang Yang , Wu Yuliang , Mu Jianjun
Published: February 2022

Background

The triglyceride-glucose index (TyG index) has emerged as a reliable surrogate marker of insulin resistance associated with arterial stiffness. However, most studies were based on a cross-sectional design, and few studies have evaluated the longitudinal impact of the TyG index on arterial stiffness. This study aimed to investigate the associations of single time point measurement and the long-term trajectory of the TyG index with arterial stiffness in a Chinese cohort.

Methods

Data are derived from the Hanzhong Adolescent Hypertension Cohort study. A total of 2480 individuals who participated in the 2017 survey was included in the cross-sectional analysis. A sample of 180 individuals from the sub-cohort with follow-up data in 2005, 2013, and 2017 was enrolled in the longitudinal analysis. The TyG index was calculated as ln (fasting triglyceride [mg/dL] × fasting glucose [mg/dL]/2), and arterial stiffness was determined using brachial-ankle pulse wave velocity (baPWV). The latent class growth mixture modeling method was used to identify the TyG index trajectories from 2005 to 2017.

Results

In the cross-sectional analysis, the median age of the study population was 42.8 (39.8, 44.9) years, and 1351 (54.5%) were males. Each one-unit increment in TyG index was associated with a 37.1 cm/s increase (95% confidence interval [CI] 23.7–50.6 cm/s; P < 0.001) in baPWV, and similar results were observed when the TyG index was in the form of quartiles. In the longitudinal analysis, we identified three distinct TyG index trajectories and found that the highest TyG index trajectory carried the greatest odds of increased arterial stiffness, with a fully adjusted odds ratio (OR) of 2.76 (95% CI 1.40, 7.54).

Conclusions

Elevated levels of baseline TyG index and higher long-term trajectory of TyG index were independently associated with increased arterial stiffness. Monitoring immediate levels and longitudinal trends of the TyG index may help with the prevention of arterial stiffness in the long run.
FK506 and Lactobacillus acidophilus ameliorate acute graft-versus-host disease by modulating the T helper 17/regulatory T-cell balance
Authors: Beak Jin-Ah , Park Min-Jung , Kim Se-Young , Jhun JooYeon , Woo Jin Seok , Choi Jeong Won , Na Hyun Sik , Lee Soon Kyu , Choi Jong Young , Cho Mi-La
Published: February 2022

Background

Graft-versus-host disease (GvHD) is a critical complication after allogeneic hematopoietic stem cell transplantation (HSCT). The immunosuppressants given to patients undergoing allogeneic HSCT disturb the microbiome and the host immune system, potentially leading to dysbiosis and inflammation, and may affect immune function and bone marrow transplantation. The intestinal microbiome is a target for the development of novel therapies for GvHD. Lactobacillus species are widely used supplements to induce production of antimicrobial and anti-inflammatory factors.

Methods

We determined the effect of the combination of Lactobacillus acidophilus and FK506 on GvHD following major histocompatibility complex-mismatched bone marrow transplantation.

Results

The combination treatment suppressed IFN-γ and IL-17-producing T cell differentiation, but increased Foxp3+Treg differentiation and IL-10 production. Also, the combination treatment and combination treated-induced Treg cells modulated the proliferation of murine alloreactive T cells in vitro. Additionally, the combination treatment upregulated Treg-related genes—Nt5e, Foxp3, Ikzf2, Nrp1 and Itgb8—in murine CD4+-T cells. The combination treatment also alleviated GvHD clinically and histopathologically by controlling the effector T cell and Treg balance in vivo. Moreover, the combination treatment decreased Th17 differentiation significantly and significantly upregulated Foxp3 and IL-10 expression in peripheral blood mononuclear cells from healthy controls and liver transplantation (LT) patients.

Conclusions

Therefore, the combination of L. acidophilus and FK506 is effective and safe for patients undergoing allogeneic hematopoietic stem cell transplantation.
Preoperative patient factors associated with blood product use in cardiac surgery, a retrospective cohort study
Authors: Eranki Aditya , Wilson-Smith Ashley , Ali Umar , Merry Christopher
Published: February 2022

Background

Cardiac surgery is associated with a high rate of blood use. The aim of this study is to identify preoperative patient factors associated with allogeneic Red Blood Cell (RBC) or non-Red Blood Cell (NRBC) use in cardiac surgery.

Methods

All adult cardiac surgical procedures conducted at a single Western Australian institution were retrospectively analysed. Data was collected from the Australia and New Zealand Cardiac Surgery Database from 2015 to 2018. A number of preoperative factors were identified, relating to past medical history or preoperative cardiac status. Outcome 1 was defined as the use of one or more RBC products intra or post-operatively. Outcome 2 was defined as the use of one or more NRBC products intra or post-operatively. Multivariate logistical regression analysis was done to assess for the association between preoperative factors and allogeneic blood product use.

Results

A total of 1595 patients were included in this study, of which 1488 underwent a Coronary Artery Bypass Graft, Valve or a combined procedure. Patients on dialysis preoperatively and those who had preoperative cardiogenic shock demonstrated the greatest risk of requiring RBC transfusion with an odds ratio of 5.643 (95% CI 1.305–24.40) and 3.257 (95% 1.801–5.882) respectively. Patients who had preoperative cardiogenic shock demonstrated the greatest risk of requiring NRBC transfusion with an odds ratio of 3.473 (95% CI 1.970–6.135). Patients who have had a previous cardiothoracic intervention are at increased risk of both RBC and NRBC transfusion, with adjusted odds ratios of 1.774 (95% CI 1.353–2.325) and 2.370 (95% CI 1.748–3.215) respectively.

Conclusion

A number of factors relating to past medical history or preoperative cardiac status are implicated with increased allogeneic blood product use in cardiac surgery. Identifying high-risk patients in a preoperative setting can enable us enrol them in a blood conservation program, therefore minimizing the risk of exposure to blood transfusion.
Transactional sex work and HIV among women in conflict-affected Northeastern Uganda: a population-based study
Authors: Mootz Jennifer J. , Odejimi Omolola A. , Bhattacharya Aishwarya , Kann Bianca , Ettelbrick Julia , Mello Milena , Wainberg Milton L. , Khoshnood Kaveh
Published: February 2022

Background

Armed conflict and the HIV pandemic are significant global health issues. Evidence of the association between armed conflict and HIV infection has been conflicting. Our objective was to examine the role of mediating risk factors, such as engagement in transactional sex work, to elucidate the relation between armed conflict and HIV infection.

Methods

We used multistage sampling across three Northeastern Ugandan districts to randomly select 605 women aged 13 to 49 to answer cross-sectional surveys from January to May of 2016. We used multivariate logistic regression model with R 4.0.3 to examine if exposure to armed conflict has an indirect effect on reporting having an HIV-positive serostatus through engagement in transactional sex work. Age and district residence were included as covariates.

Results

Exposure to armed conflict β = .16, SE = .04, p < .05, OR = 1.17, 95% [CI .08, .23] was significantly associated with reporting a HIV-positive serostatus. For each 1-unit increase in exposure to armed conflict (i.e., additional type of armed conflict exposure), there was a 17% increase in the odds of reporting a HIV-positive serostatus. Engagement in transactional sex work was not associated with reporting a HIV-positive serostatus β = .04, SE = .05, p = .37, 95% [CI − .051, .138]. We found district of residence, age, and interaction effects.

Conclusions

Although exposure to armed was associated with reporting an HIV-positive serostatus, this relationship was not mediated by engagement in transactional sex. Further research is needed on risk factors that mediate this relationship. The likelihood of reporting a HIV-positive serostatus increased with each additional type of exposure to armed conflict. Thus, screening for exposure to multiple traumatic stressors should occur in HIV prevention settings. Healthcare services that are trauma-informed and consider mental distress would likely improve HIV outcomes.
Giant carotid chemodectoma treated with a combination of surgery and CyberKnife radiotherapy: a case report and review of the literature
Authors: López-Arcas José M. , Colmenero César M. , Martínez Roberto , Martín-Hernán Fátima , Ruiz-Sánchez Beatriz , Aragoneses Juan Manuel
Published: February 2022

Background

Paragangliomas are rare vascular neuroendocrine tumors that develop in the extra-adrenal paraganglion tissue. They occur most commonly at the carotid bifurcation, where they are known as carotid body tumors. Most paragangliomas are benign, locally aggressive, infiltrative tumors. Approximately 10% of patients with paragangliomas develop distant metastases, 10% present with multiple or bilateral tumors (mostly carotid body tumors), and 10% have a family history of paragangliomas. The malignant transformation of carotid body tumors has been reported in 6% of cases.

Case presentation

We present the case of a 64 year-old Caucasian woman with a gigantic glomic tumor mass in the neck. Twenty years before the consultation, the patient had undergone an unsuccessful attempt to remove the mass. Over the last 3 years, the patient had felt enlargement of the mass at an increased rate, almost doubling the prior size. Angio magnetic resonance imaging showed a 9 cm paratracheal mass on the left cervical side that laterally displaced the sternocleidomastoid muscle and 2 c m of the trachea. Due to the change in the tumor behavior, the maxillofacial team at Ruber International Hospital decided to remove the tumor surgically after embolization. During the surgery the tumor was gently dissected from the carotid an removed from the carotid bifurcation uneventfully. Two small nodes adhering tightly to the internal carotid adventitia and the posterior torn hole were left in place to avoid any potentially life-threatening complications. The final biopsy confirmed the initial diagnosis of carotid body paraganglioma and showed a Ki-67 expression of 19%. Due to the aggressive growth behavior and high Ki-67 expression of the tumor, the patient was referred to the CyberKnife Unit of Ruber International Hospital for treatment of the remaining nodes.

Conclusions

The management of cervical paragangliomas is difficult and remains a challenge. Although the likelihood of tumor control is high with surgical or radiotherapeutic treatments, we currently lack consensus regarding the best treatment option. Nevertheless, in selected complex cases, such as the case we present, the combination of surgery and radiosurgery may allow complete local tumor control with minimal morbidity.
A machine learning based credit card fraud detection using the GA algorithm for feature selection
Authors: Ileberi Emmanuel , Sun Yanxia , Wang Zenghui
Published: February 2022

The recent advances of e-commerce and e-payment systems have sparked an increase in financial fraud cases such as credit card fraud. It is therefore crucial to implement mechanisms that can detect the credit card fraud. Features of credit card frauds play important role when machine learning is used for credit card fraud detection, and they must be chosen properly. This paper proposes a machine learning (ML) based credit card fraud detection engine using the genetic algorithm (GA) for feature selection. After the optimized features are chosen, the proposed detection engine uses the following ML classifiers: Decision Tree (DT), Random Forest (RF), Logistic Regression (LR), Artificial Neural Network (ANN), and Naive Bayes (NB). To validate the performance, the proposed credit card fraud detection engine is evaluated using a dataset generated from European cardholders. The result demonstrated that our proposed approach outperforms existing systems.
Investigation of geomagnetic reference models based on the Iridium$$^{\circledR }$$ constellation
Authors: Califf Samuel , Alken Patrick , Chulliat Arnaud , Anderson Brian , Rock Kenneth , Vines Sarah , Barnes Robin , Liou Kan
Published: February 2022

The World Magnetic Model (WMM) is a geomagnetic main field model that is widely used for navigation by governments, industry and the general public. In recent years, the model has been derived using high accuracy magnetometer data from the Swarm mission. This study explores the possibility of developing future WMMs in the post-Swarm era using data from the Iridium satellite constellation. Iridium magnetometers are primarily used for attitude control, so they are not designed to produce the same level of accuracy as magnetic data from scientific missions. Iridium magnetometer errors range from 30 nT quantization to hundreds of nT errors due to spacecraft contamination and calibration uncertainty, whereas Swarm measurements are accurate to about 1 nT. The calibration uncertainty in the Iridium measurements is identified as a major error source, and a method is developed to calibrate the spacecraft measurements using data from a subset of the INTERMAGNET observatory network producing quasi-definitive data on a regular basis. After calibration, the Iridium data produced main field models with approximately 20 nT average error and 40 nT maximum error as compared to the CHAOS-7.2 model. For many scientific and precision navigation applications, highly accurate Swarm-like measurements are still necessary, however, the Iridium-based models were shown to meet the WMM error tolerances, indicating that Iridium is a viable data source for future WMMs.

Graphical Abstract
Prediction of glomerular filtration rate maturation across preterm and term neonates and young infants using inulin as marker
Authors: Wu Yunjiao , Allegaert Karel , Flint Robert B. , Simons Sinno H. P. , Krekels Elke H. J. , Knibbe Catherijne A. J. , Völler Swantje
Published: February 2022

Describing glomerular filtration rate (GFR) maturation across the heterogeneous population of preterm and term neonates and infants is important to predict the clearance of renally cleared drugs. This study aims to describe the GFR maturation in (pre)term neonates and young infants (PNA < 90 days) using individual inulin clearance data (CLinulin). To this end, published GFR maturation models were evaluated by comparing their predicted GFR with CLinulin retrieved from literature. The best model was subsequently optimized in NONMEM V7.4.3 to better fit the CLinulin values. Our study evaluated seven models and collected 381 individual CLinulin values from 333 subjects with median (range) birthweight (BWb) 1880 g (580–4950), gestational age (GA) 34 weeks (25–43), current weight (CW) 1890 g (480–6200), postnatal age (PNA) 3 days (0–75), and CLinulin 2.20 ml/min (0.43–17.90). The De Cock 2014 model (covariates: BWb and PNA) performed the best in predicting CLinulin, followed by the Rhodin 2009 model (covariates: CW and postmenstrual age). The final optimized model shows that GFR at birth is determined by BWb, thereafter the maturation rate of GFR is dependent on PNA and GA, with a higher GA showing an overall faster maturation. To conclude, using individual CLinulin data, we found that a model for neonatal GFR requires a distinction between prenatal maturation quantified by BWb and postnatal maturation. To capture postnatal GFR maturation in (pre)term neonates and young infants, we developed an optimized model in which PNA-related maturation was dependent on GA.

Graphical abstract
Inadvertent Placement of an Infraclavicular Catheter in the Interscalene Region With an Unusual Complication: A Case Report
Authors: Osterc Tea , Rupnik Barbara , Rosskopf Andrea B. , Borgeat Alain , Eichenberger Urs , Aguirre José
Published: February 2022

An infraclavicular catheter is a very efficient technique to provide excellent perioperative anesthesia/analgesia for upper limb surgery. However, complications can occur and are dependent on the technique used. We report the inadvertent placement of an infraclavicular catheter in the interscalene region when an ultrasound-guided infraclavicular catheter was threaded cranially. We proposed some strategies to avoid the occurrence of complications when performing this block.
Marie de Gournay’s “Advis à quelques gens d’Église” and the Early Modern Rigorist Debate
Authors: Conroy Derval
Published: February 2022

This article examines one of Marie de Gournay’s forays into religious controversy in her short text “Advis à quelques gens d’Église.” First published in L’Ombre de la damoiselle de Gournay (1626), the text is an indictment of the abuse of the sacrament of confession by both penitents and confessors, and points to a rigorist stance on the part of the author nearly twenty years before it became the dominant position of the church once again. Tackling a range of thorny questions such as the aim of confession, deferred absolution, and the nature of sin, Gournay examines confession as a societal institution, outlining how it fails utterly to reduce the daily experience of petty injustices and wrongdoing. Placing that failure squarely at the feet of the clergy, Gournay includes advice for the confessors, making of the text a secular “manuel des confesseurs”—an extraordinary undertaking for a laywoman at the time.
“Vivre avec les vivants”
Authors: Seifert Lewis C.
Published: February 2022

Starting from the premise that the study of quarrels—and especially those involving women—has much to gain by considering conflicts that do not involve an appeal to a public, this essay focuses on the case of Madeleine de Souvré, marquise de Sablé (1599–1678), who articulated a theory of conflict in her “Maximes” and was involved with several high-profile controversies through her friendships with François de La Rochefoucauld and the nuns of Port-Royal de Paris. In her theory and practice of conflict, Sablé develops an art of ambiguity that strives for both individual agency and interpersonal harmony. Throughout her maxims, she lays out explicit strategies for managing conflicts but is caught between an emphasis on gaining an advantage over one’s adversaries and, at the other extreme, finding a middle ground with them. But conflicts from her life suggest a different art of ambiguity: through her involvement with the first readers of La Rochefoucauld’s Maximes and her relations with the nuns of Port-Royal, Sablé aims to preserve her own viewpoint and her friendships at the same time. These ambiguities lead to the hypothesis that she faced gendered limits that pushed her to search for ways of making her opinions more palatable and, ultimately, of allowing them to coexist with diverging opinions.
In Search of Lost Snails
Authors: van Dooren Thom
Published: February 2022

The Hawaiian Islands were once home to one of the most diverse assemblages of terrestrial snails found anywhere on earth, with more than 750 recognized species. Today, however, the majority of these species are extinct, and most of those that remain are headed swiftly in the same direction. But this is just the crisis that we know about, that we can in some way quantify. In Hawai‘i, and all over the world, a diversity of species—many of them invertebrates—are being lost while they still remain unknown to science. In fact, for every described species that blinks out, the best estimates indicate that roughly another four extinctions take place entirely unknown to us. This article focuses on the particular case of Hawai‘i’s snails and the efforts of taxonomists to catalog them as a way into this broader unknown extinction crisis. Snails have particular lessons to offer in understanding and responding to this situation. This article seeks to draw out those lessons, thinking through some of the challenges for storytelling in summoning up these unseen others and in opening up a space for ethical encounter with living and dead beings that must, in important ways, remain beyond the edges of our knowledge.
Child Minds at the End of the World
Authors: Caracciolo Marco
Published: February 2022

This article focuses on the evocation of children’s experiences in fiction that engages with postapocalyptic scenarios. It examines three contemporary novels from profoundly different geographic contexts—Yoko Tawada’s The Emissary, Niccolò Ammaniti’s Anna, and Diane Cook’s The New Wilderness—that evoke a child’s experience of societal collapse in the wake of a catastrophic event. Diverse meanings come to the fore as these novels outline, through child focalization, the relevance of bodily experience, materiality, and reenchantment vis-à-vis the climate crisis and its uncertainties. This discussion shows how formal choices in climate fiction are instrumental in creating an affective trajectory that complicates adult readers’ perception of our collective future. These close readings stage an encounter between the fields of ecocriticism and childhood studies that speaks to the significance of the figure of the child in the environmental humanities: even in literature by and for adults, the integration of children’s perspectives on the end of the world performs important cultural work by questioning and decentering an understanding of the ecological crisis shaped exclusively by the adult (and adultist) anxieties of parenthood.
Agency and Multispecies Communities in Picture Books
Authors: Duckworth Melanie
Published: February 2022

This article discusses two children’s picture books, The Snail and the Whale (2003), written by Julia Donaldson and illustrated by Axel Scheffler, and The Secret of Black Rock (2017) by Joe Todd-Stanton, as vibrant and fantastic engagements with multispecies worlds. Drawing on new materialism and multispecies studies, the article argues that these two picture books exemplify the possibilities inherent in children’s literature of imaging encounters with multispecies communities and apprehending the dynamic agencies of the material world. With reference to the real marine animals and environments alluded to by the books, it addresses the limitations and opportunities of anthropomorphism, and the significance of the concept of agency in the environmental humanities and children’s literature studies. It argues that the gleeful rhymes of The Snail and the Whale and the awe-inspiring illustrations of The Secret of Black Rock are not mere entertainment but serious and playful explorations of connections between bodies and language, stories and communities, children and adults, human and non-human animals, rocks and fish, and agency and the more-than-human world.