bluuebunny/crossref_metadata_2025 huggingface dataset:
Biosimilar competition in European markets of TNF-alpha inhibitors: a comparative analysis of pricing, market share and utilization trends
Authors: Car Elif , Vulto Arnold G. , Houdenhoven Mark Van , Huys Isabelle , Simoens Steven
Published: April 2023

Background: Factors like the number of biosimilar competitors and competitive pricing strategies from originator companies may influence price competition and biosimilar uptake.

Objective: The aim of this study was to analyze multiple facets of biosimilar competition of TNF-alpha inhibitors in Europe by exploring the existence of a biosimilar first-mover advantage, pricing strategies of originator companies, and the evolution in patient access.

Methods: Sales and volume data on biosimilar and originator infliximab, etanercept, and adalimumab between 2008 and 2020 were provided by IQVIA. Countries included 24 European Union Member States, Norway, Switzerland, United Kingdom, Serbia, and Bosnia and Herzegovina. Sales value was expressed as ex-manufacturer price per defined daily dose (DDD), and volume data were transformed into the number of DDDs per 1,000 inhabitants per day. Descriptive analyses were conducted based on the evolution in price per DDD, trends in biosimilar and originator market shares and utilization trends.

Results: Market entry of the first biosimilars of infliximab and adalimumab resulted in a decrease of the volume-weighted average price (VWAP) per DDD by 13.6% and 0.9% on average, whilst the second biosimilars resulted in a decrease by 26.4% and 27.3%, respectively. The first and second etanercept biosimilars generated a similar decrease in the VWAP per DDD by 9.3% and 9.1% on average, respectively. Average market share captured by the first biosimilars was at least twice as large as the second biosimilars for all molecules. In addition, sharp reductions in price per DDD of Humira® in most countries indicated a pricing strategy resulting in low uptake of adalimumab biosimilars. Lastly, utilization of infliximab, etanercept, and adalimumab following biosimilar entry increased by an average of 88.9%, 14.6%, and 22.4%, respectively. However, introduction of (multiple) biosimilar competitors did not necessarily translate into increase in treatment access for all three molecules across some European countries indicating a shift in utilization from one molecule towards the other(s).

Conclusion: Overall, this study revealed that biosimilar entry results in increased utilization and price reduction, although at a heterogenous rate among TNF-alpha inhibitors. Observed trends in market shares indicate a biosimilar first-mover advantage whereas pricing strategies considered to be anti-competitive can limit market uptake.
Polypharmacy and associated factors: a gender perspective in the elderly Spanish population (2011–2020)
Authors: Cebrino Jesús , Portero de la Cruz Silvia
Published: April 2023

Background: Few studies have examined the epidemiology of polypharmacy in non-institutionalized elderly adults with regard to sex differences. This study aimed to identify the prevalence of polypharmacy among people ≥65 years old residing in Spain, analyze trends in that prevalence from 2011/12 to 2020, describe the use of the medicines involved and study the possible relationship between polypharmacy and certain sociodemographic, health-related variables, as well as the use of care services by sex.

Methods: A nationwide cross-sectional study with 21,841 non-institutionalized people ≥65 years old from the Spanish National Health Survey (2011/2012 and 2017) and the European Health Survey in Spain (2014 and 2020) was performed. We used descriptive statistics, performing two binary logistic regressions to determine the factors related to polypharmacy.

Results: The prevalence of polypharmacy was 23.2% (women: 28.1%, men: 17.2%; p < 0.001). The most commonly consumed medicines were analgesics and tranquillizers, relaxants or sleeping pills in elderly women, compared with antihypertensives, antacids and antiulcer drugs and statins for elderly men. In both sexs, the positive predictors of polypharmacy included average, poor and very poor self-perceived states of health, people with overweight and obesity, being severely/non-severely limited due to a health problem, having ≥ three chronic conditions, visits to the family doctor and hospitalization. Among elderly women, negative predictors were alcohol intake, whereas in elderly men positive predictors were being 75–84 years old, being current smokers and having 1, 2 chronic conditions.

Conclusion: Polypharmacy has a prevalence of 23.2%, with women accounting for 28.1% and men 17.2% of the total. Knowledge of positive and negative predictors of polypharmacy have important implications for public health efforts to develop or improve health guidelines and strategies for promoting the proper use of medication, particularly in the elderly population by sex.
The crosstalk between BAT thermogenesis and skeletal muscle dysfunction
Authors: Chen Yao , Hu Qian , Wang Changyi , Wang Tiantian
Published: April 2023

Metabolic defects increase the risk of skeletal muscle diseases, and muscle impairment might worsen metabolic disruption, leading to a vicious cycle. Both brown adipose tissue (BAT) and skeletal muscle play important roles in non-shivering thermogenesis to regulate energy homeostasis. BAT regulates body temperature, systemic metabolism, and seretion of batokines that have positive or negative impacts on skeletal muscle. Conversely, muscle can secrete myokines that regulate BAT function. This review explained the crosstalk between BAT and skeletal muscle, and then discussed the batokines and highlighted their impact on skeletal muscle under physiological conditions. BAT is now considered a potential therapeutic target for obesity and diabetes treatment. Moreover, manipulation of BAT may be an attractive approach for the treatment of muscle weakness by correcting metabolic deficits. Therefore, exploring BAT as a potential treatment for sarcopenia could be a promising avenue for future research.
Machine learning for screening of at-risk, mild and moderate COPD patients at risk of FEV1 decline: results from COPDGene and SPIROMICS
Authors: Wang Jennifer M. , Labaki Wassim W. , Murray Susan , Martinez Fernando J. , Curtis Jeffrey L. , Hoffman Eric A. , Ram Sundaresh , Bell Alexander J. , Galban Craig J. , Han MeiLan K. , Hatt Charles
Published: April 2023

Purpose: The purpose of this study was to train and validate machine learning models for predicting rapid decline of forced expiratory volume in 1 s (FEV1) in individuals with a smoking history at-risk-for chronic obstructive pulmonary disease (COPD), Global Initiative for Chronic Obstructive Lung Disease (GOLD 0), or with mild-to-moderate (GOLD 1–2) COPD. We trained multiple models to predict rapid FEV1 decline using demographic, clinical and radiologic biomarker data. Training and internal validation data were obtained from the COPDGene study and prediction models were validated against the SPIROMICS cohort.

Methods: We used GOLD 0–2 participants (n = 3,821) from COPDGene (60.0 ± 8.8 years, 49.9% male) for variable selection and model training. Accelerated lung function decline was defined as a mean drop in FEV1% predicted of > 1.5%/year at 5-year follow-up. We built logistic regression models predicting accelerated decline based on 22 chest CT imaging biomarker, pulmonary function, symptom, and demographic features. Models were validated using n = 885 SPIROMICS subjects (63.6 ± 8.6 years, 47.8% male).

Results: The most important variables for predicting FEV1 decline in GOLD 0 participants were bronchodilator responsiveness (BDR), post bronchodilator FEV1% predicted (FEV1.pp.post), and CT-derived expiratory lung volume; among GOLD 1 and 2 subjects, they were BDR, age, and PRMlower lobes fSAD. In the validation cohort, GOLD 0 and GOLD 1–2 full variable models had significant predictive performance with AUCs of 0.620 ± 0.081 (p = 0.041) and 0.640 ± 0.059 (p < 0.001). Subjects with higher model-derived risk scores had significantly greater odds of FEV1 decline than those with lower scores.

Conclusion: Predicting FEV1 decline in at-risk patients remains challenging but a combination of clinical, physiologic and imaging variables provided the best performance across two COPD cohorts.
The role and mechanism of the gut microbiota in the development and treatment of diabetic kidney disease
Authors: Wu Xiaofang , Zhao Lei , Zhang Yujiang , Li Kailong , Yang Jurong
Published: April 2023

Diabetic kidney disease (DKD) is a common complication in patients with diabetes mellitus (DM). Increasing evidence suggested that the gut microbiota participates in the progression of DKD, which is involved in insulin resistance, renin-angiotensin system (RAS) activation, oxidative stress, inflammation and immunity. Gut microbiota-targeted therapies including dietary fiber, supplementation with probiotics or prebiotics, fecal microbiota transplantation and diabetic agents that modulate the gut microbiota, such as metformin, glucagon-like peptide-1 (GLP-1) receptor agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, and sodium-glucose transporter-2 (SGLT-2) inhibitors. In this review, we summarize the most important findings about the role of the gut microbiota in the pathogenesis of DKD and the application of gut microbiota-targeted therapies.
The combination of salt and drought benefits selective ion absorption and nutrient use efficiency of halophyte Panicum antidotale
Authors: Hussain Tabassum , Asrar Hina , Zhang Wensheng , Liu Xiaojing
Published: April 2023

Soil salinity and water deficit often occur concurrently, but understanding their combined effects on plants’ ion regulation is limited. With aim to identify if introducing drought with salinity alleviates salt stress’s ionic effects, Panicum antidotale – a halophytic grass- was grown in the presence of single and combined stressors, i.e., drought and salt (low and high). Regulation of cations and anions along with the antioxidant capacity and modifications in leaf anatomy were investigated. Results showed a combination of low salt and drought minimally affected plant (dry) mass by improving the selective ions absorption and nutrient use efficiencies. The lowest ratio for efficiency of photosystem II and carbon assimilation (ΦPSII/ΦCO2) suggested less generation of reactive oxygen species, which were probably detoxified with constitutively performing antioxidant enzymes. In contrast, the combination of high salinity and drought escalated the adverse effects caused due to individual stressors. The selective ion absorption increased, but the non-selective ions transport caused an ionic imbalance indicating the highest ratio of Na+/K+. Although the area of mesophyll increased, a reduction in epidermis (cell number and area) predicted a mechanical injury prone to water loss in these plants. The compromised activity of antioxidant enzymes also suggested treatment-induced oxidative damage. Yet, the synergistic interaction between high salinity and drought was not detrimental to the survival of P. antidotale. Therefore, we suggest planting this grass in habitats with harsh environmental conditions to meet the increasing fodder demands without compromising agricultural lands’ productivity.
Distinct role of AtCuAOβ- and RBOHD-driven H2O2 production in wound-induced local and systemic leaf-to-leaf and root-to-leaf stomatal closure
Authors: Fraudentali Ilaria , Pedalino Chiara , D’Incà Riccardo , Tavladoraki Paraskevi , Angelini Riccardo , Cona Alessandra
Published: April 2023

Polyamines (PAs) are ubiquitous low-molecular-weight aliphatic compounds present in all living organisms and essential for cell growth and differentiation. The developmentally regulated and stress-induced copper amine oxidases (CuAOs) oxidize PAs to aminoaldehydes producing hydrogen peroxide (H2O2) and ammonia. The Arabidopsis thaliana CuAOβ (AtCuAOβ) was previously reported to be involved in stomatal closure and early root protoxylem differentiation induced by the wound-signal MeJA via apoplastic H2O2 production, suggesting a role of this enzyme in water balance, by modulating xylem-dependent water supply and stomata-dependent water loss under stress conditions. Furthermore, AtCuAOβ has been shown to mediate early differentiation of root protoxylem induced by leaf wounding, which suggests a whole-plant systemic coordination of water supply and loss through stress-induced stomatal responses and root protoxylem phenotypic plasticity. Among apoplastic ROS generators, the D isoform of the respiratory burst oxidase homolog (RBOH) has been shown to be involved in stress-mediated modulation of stomatal closure as well. In the present study, the specific role of AtCuAOβ and RBOHD in local and systemic perception of leaf and root wounding that triggers stomatal closure was investigated at both injury and distal sites exploiting Atcuaoβ and rbohd insertional mutants. Data evidenced that AtCuAOβ-driven H2O2 production mediates both local and systemic leaf-to-leaf and root-to-leaf responses in relation to stomatal movement, Atcuaoβ mutants being completely unresponsive to leaf or root wounding. Instead, RBOHD-driven ROS production contributes only to systemic leaf-to-leaf and root-to-leaf stomatal closure, with rbohd mutants showing partial unresponsiveness in distal, but not local, responses. Overall, data herein reported allow us to hypothesize that RBOHD may act downstream of and cooperate with AtCuAOβ in inducing the oxidative burst that leads to systemic wound-triggered stomatal closure.
Fine mapping and identifying candidate gene of Y underlying yellow peel in Cucurbita pepo
Authors: Niu Jianqing , Chen Qiong , Lu Xiaonan , Wang Xueqiang , Tang Zhongli , Liu Qinghua , Lei Fengjin , Xu Xiaoyong
Published: April 2023

As a conspicuous trait, peel color is one of the most important characteristics that affects commodity quality and consumer preferences. The locus Y underlying yellow peel in Cucurbita pepo (zucchini) was first reported in 1922; however, its molecular mechanism is still unknown. In this study, a genetic analysis revealed that yellow peel is controlled by a single dominant genetic factor. Furthermore, Y was mapped in a ~170 kb region on chromosome 10 by bulked segregated analysis (BSA) and fine mapping in F2 and BC1 segregating populations. The candidate region harbors fifteen annotated genes, among which Cp4.1LG10g11560 (CpCHLH) is regarded as a promising candidate gene. CpCHLH encodes a magnesium chelatase H subunit involved in chlorophyll biosynthesis, and its mutation can result in a reduction in chlorophyll content and yellow phenotype. Interestingly, a large fragment (~15 kb) duplication containing incomplete CpCHLH was inserted in the candidate interval, resulting in two reformed CpCHLH proteins in the yellow parental line. It is most likely that the reformed CpCHLH proteins act as a malfunctional competitor of the normal CpCHLH protein to interrupt the formation of chlorophyll. Overall, the isolation of Y will shed light on the molecular mechanism of the peel color regulation of zucchini and lay a foundation for breeding.
Low nitrogen stress-induced transcriptome changes revealed the molecular response and tolerance characteristics in maintaining the C/N balance of sugar beet (Beta vulgaris L.)
Authors: Li Jiajia , Liu Xinyu , Xu Lingqing , Li Wangsheng , Yao Qi , Yin Xilong , Wang Qiuhong , Tan Wenbo , Xing Wang , Liu Dali
Published: April 2023

Nitrogen (N) is an essential macronutrient for plants, acting as a common limiting factor for crop yield. The application of nitrogen fertilizer is related to the sustainable development of both crops and the environment. To further explore the molecular response of sugar beet under low nitrogen (LN) supply, transcriptome analysis was performed on the LN-tolerant germplasm ‘780016B/12 superior’. In total, 580 differentially expressed genes (DEGs) were identified in leaves, and 1,075 DEGs were identified in roots (log2|FC| ≥ 1; q value < 0.05). Gene Ontology (GO), protein−protein interaction (PPI), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses clarified the role and relationship of DEGs under LN stress. Most of the downregulated DEGs were closely related to “photosynthesis” and the metabolism of “photosynthesis-antenna proteins”, “carbon”, “nitrogen”, and “glutathione”, while the upregulated DEGs were involved in flavonoid and phenylalanine biosynthesis. For example, GLUDB (glutamate dehydrogenase B) was identified as a key downregulated gene, linking carbon, nitrogen, and glutamate metabolism. Thus, low nitrogen-tolerant sugar beet reduced energy expenditure mainly by reducing the synthesis of energy-consuming amino acids, which in turn improved tolerance to low nitrogen stress. The glutathione metabolism biosynthesis pathway was promoted to quench reactive oxygen species (ROS) and protect cells from oxidative damage. The expression levels of nitrogen assimilation and amino acid transport genes, such as NRT2.5 (high-affinity nitrate transporter), NR (nitrate reductase [NADH]), NIR (ferredoxin-nitrite reductase), GS (glutamine synthetase leaf isozyme), GLUDB, GST (glutathione transferase) and GGT3 (glutathione hydrolase 3) at low nitrogen levels play a decisive role in nitrogen utilization and may affect the conversion of the carbon skeleton. DFRA (dihydroflavonol 4-reductase) in roots was negatively correlated with NIR in leaves (coefficient = −0.98, p < 0.05), suggesting that there may be corresponding remote regulation between “flavonoid biosynthesis” and “nitrogen metabolism” in roots and leaves. FBP (fructose 1,6-bisphosphatase) and PGK (phosphoglycerate kinase) were significantly positively correlated (p < 0.001) with Ci (intercellular CO2 concentration). The reliability and reproducibility of the RNA-seq data were further confirmed by real-time fluorescence quantitative PCR (qRT−PCR) validation of 22 genes (R2 = 0.98). This study reveals possible pivotal genes and metabolic pathways for sugar beet adaptation to nitrogen-deficient environments.
Prokaryotic diversity and community structure in the rhizosphere of Lantana weed (Lantana camara L.)
Authors: Gola Upasana , Kour Shilippreet , Kaur Tanvir , Perveen Kahkashan , Bukhari Najat A. , Alsulami Jamilah A. , Maithani Damini , Dasila Hemant , Singh Manali , Suyal Deep Chandra
Published: April 2023

Lantana weed (Lantana camara L.) is among the most noxious weeds in the world. Keeping in mind its invasive behavior and great ecological tolerance, it becomes imperative to analyze the structure and function of associated microbiome. In this perspective, Illumina-based metagenome sequencing was performed to gain a better understanding of prokaryotic diversity and community structure in the rhizosphere soil of L. camara L. The organic carbon, nitrogen, phosphorus, and potassium contents in the rhizosphere soil were 0.91% (± 0.21%); 280 Kg ha-1 (± 4.02 Kg ha-1), 54.5 Kg ha-1 (± 3.12 Kg ha-1), and 189 Kg ha-1 (± 6.11 Kg ha-1), respectively. The metagenome analysis revealed the existence of 41 bacterial and 2 archaeal phyla, with only 12 showing ≥1% abundances. Pseudomonadota was the dominant phylum with 31.3% abundance, followed by Actinomycetota (20.9%). Further, 54 different genera were identified with the highest abundance of Devosia (2.8%). The PICRUSt analysis predicted various functional traits in the soil metagenome, with general cellular functions dominating, followed by stress tolerance. Moreover, 10% of the functions were associated with nitrogen fixation, phosphate solubilization, and potassium mobilization. In conclusion, the present study revealed the existence of diverse prokaryotic communities in the rhizosphere of the L. camara L. which was primarily associated with stress response and plant growth promotion. To the best of our knowledge, this study documents for the first time the L. camara L. microbiome. Furthermore, the identified genera can be explored for agricultural needs in future.
Individual differences in environmental wellbeing and pro-environmental behaviors explained by self-control
Authors: Strömbäck Camilla , Lindkvist Emma , Västfjäll Daniel
Published: April 2023

Climate change is an increasing problem, with more extreme weather conditions and rising temperatures. To fulfill the temperature goals of the Paris agreement a societal change is needed, a change that requires a shift of lifestyle from all of us. If we want to change our behaviors to more sustainable ones, we need to sacrifice substantial things today to improve a future, which often seems distant and abstract. People with high level of self-control have been shown to have a better ability to visualize future events, which makes self-control an interesting trait to look at in relation to pro-environmental behavior. The aim of this study was to examine how self-control correlates with environmental well-being and environmental behavior. An internet-based survey was sent to a representative Swedish sample (n = 602). The respondents were asked to fill out a newly developed scale measuring their anxiety and security regarding environmental matters (environmental wellbeing), as well as indicate how often they engage in six different pro-environmental behaviors (e.g., turning lights off when leaving the room). Additionally, data on the respondents’ gender, age, political orientation, and self-control was collected. Our results suggest a positive correlation between self-control and environmental wellbeing and a weaker, but still positive, correlation between self-control and some pro-environmental behaviors. Additionally, respondents who identified themselves as politically left had lower environmental wellbeing, while men had higher environmental wellbeing, but behaved less environmentally friendly. Thus, our results suggest that political orientation was a better predictor of sound environmental behavior than subjective self-control was.
Didactics of written argumentation with Spanish as a Foreign Language (SFL) students at university level in Algeria
Authors: Baaziz Saida , de Vicente-Yagüe Jara María Isabel
Published: April 2023

The general objective of this research is to investigate the impact of a program focusing on the development of argumentation techniques on the improvement of critical essays by SFL students at the University of Algiers 2. A quasi-experimental pretest-posttest study was carried out, where the indicators of textual levels obtained by the students were evaluated and compared, both before and after a learning intervention. The study involved 126 students studying SFL at the University of Algiers 2, whose essays were analyzed using Parodi and Núñez’s (1999) analysis guidelines, in order to evaluate the students’ argumentative competence at the three levels of microstructure, macrostructure and superstructure. Once the results were analyzed, statistically significant differences were observed in the indicators of the macrostructure, and superstructure. Furthermore, an improvement in the post-test means is observed in the indicators of these microstructure. Lastly, the intervention program strengthened students’ argumentative abilities, which had a significant effect on their critical essays.
Lower serum insulin-like growth factor 1 concentrations in patients with chronic insomnia disorder
Authors: Zhang Yanan , Sun Qingqing , Li Huimin , Wang Dong , Wang Ying , Wang Zan
Published: April 2023

Objectives

Insulin-like growth factor 1 (IGF-1) is a crucial neurotrophin that is produced in the brain and periphery and may play an important role in insomnia and mood disorders. We aimed to analyze its serum concentrations in patients with chronic insomnia disorder (CID).

Methods

Patients with CID were enrolled in this study and divided into the CID group [Generalized Anxiety Disorder-7 (GAD-7) score < 10] and the CID with anxiety group (GAD-7 score ≥ 10). Age-and sex-matched healthy volunteers were recruited as controls. The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality and the GAD-7 and the Patient Health Questionnaire-9 to assess emotional status. All subjects were monitored via polysomnography, and the serum IGF-1 concentrations in their peripheral blood were detected via enzyme-linked immunosorbent assays.

Results

We enrolled 65 patients with CID (of whom 35 had anxiety) and 36 controls. The PSQI score and IGF-1 concentration in the CID and CID with anxiety groups were higher than those in the control group. The apparent difference in IGF-1 concentration between the CID and CID with anxiety groups was not statistically significant. The IGF-1 concentration in patients with CID was linearly correlated with the GAD-7 score, PSQI score, and stage 3 non-rapid eye movement (stage N3) time.

Conclusion

The serum IGF-1 concentration in patients with CID was lower than that of participants without CID, negatively correlated with anxiety score and sleep quality, and positively correlated with stage N3 time.
Case series: Continued remission of PTSD symptoms after discontinuation of prazosin
Authors: Richardson Christie , Yuh Jonathan , Su Jing , Forsberg Martin
Published: April 2023

Post-traumatic stress disorder is a debilitating chronic illness that affects 6 out of 100 adults after a severe trauma. The alpha-adrenergic antagonist prazosin, which is prescribed off-label for flashbacks and nightmares due to trauma, is often continued indefinitely due to reports of symptoms returning upon discontinuation. There is no standard guidance for a trial of discontinuation of prazosin due to intolerance or side effects. In this case series, three patients are started on prazosin leading to remission of trauma-related symptoms, and symptoms continue to remit after treatment for an average of about 2 years followed by discontinuation of the medication. There are many similarities in these case reports which serve to provide guidance as to when a trial of prazosin discontinuation may be warranted.
Internal migration and utilization of reproductive and maternity care among women in Pakistan: evidence from a recent National Survey
Authors: Dadras Omid , Nakayama Takeo , Kihara Masahiro
Published: April 2023

Background

During the last decades, migratory behavior has had a key role in population growth and redistribution in Pakistan. Migration has far-reaching socioeconomic implications for individuals and society at large that could influence the health integrity of Pakistani women. This study aimed to describe the migration patterns and drivers as well as their association with adequate access to reproductive and maternal care among married Pakistani women aged 15–49.

Methods

The data from the 2017–18 Pakistan Demographic Health Survey (PDHS) was used to extract the information on the explanatory (sociodemographic and migration backgrounds) and outcome variables (unmet needs for family planning, adequate antenatal care, and delivery at health facilities). Bivariate and multivariate logistic regression analyses were employed to examine the relationship between these explanatory and outcome variables before and after adjustment for sociodemographic inequalities.

Results

In unadjusted models, the odds of having adequate ANC and delivery at health facilities were approximately 2 to 4 times higher in those living (urban non-migrant), moving to (urban to urban, rural to urban), or leaving the urban areas (rural to urban) as compared to rural non-migrants; likewise, the odds of the unmet needs for family planning was about 20–50% lower in the same migration streams compared to rural non-migrant. However, after adjustment for sociodemographic inequalities, most of these associations attenuated and only the association of urban to urban migration with unmet needs for family planning and the association of urban non-migrant with delivery at health facilities remained significant.

Conclusion

Although the findings suggest that Internal migration flows, particularly those to urban areas (urban to urban and rural to urban), could be associated with better access to reproductive and maternity care among married Pakistani women aged 15–49 years; adjustment for sociodemographic inequalities, particularly education and wealth, nullified this association to a great extent. This has important implications for current policies and interventions in Pakistan and calls for policy reform and women’s rights advocacy to enhance the literacy level of young Pakistani girls through well-tailored interventions, maintaining them at school.
Mapping the trends of sustainable supply chain management research: a bibliometric analysis of peer-reviewed articles
Authors: Amofa Birago , Oke Adekunle , Morrison Zoe
Published: April 2023

This bibliometric analysis explores the scope and knowledge base of scholarly efforts on sustainable supply chain management (SSCM) and how it has evolved in different economies and businesses to advance circular economy (CE) discourses in theory and practice across economies and businesses. Using the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines and search syntax, a total of 2,574 peer-reviewed articles from journals indexed in Web of Science, Scopus, and ProQuest were analyzed. The results show an exponential growth in SSCM research since 2013 with 6,306 authors from 83 countries published in 675 journals; however, less attention is given to developing economies (DEs) and Micro, Small and Medium Enterprises (MSMEs). The findings provide a useful direction for future research and theory development in SSCM, allowing scholars and businesses to implement true CE by addressing practical sustainability issues relevant to their operations and supply chains. This bibliometric analysis is the first study providing a holistic overview of SSCM research trends in developed countries (DCs), DEs, and MSMEs, and arguing for inter-disciplinary CE discourses and inter-organizational collaboration in SC to update and implement CE. This study makes important contributions to SSCM research and practice by providing multiple snapshots of the increasing growth trajectory of the idea of sustainability in SC and how its different aspects have evolved over the period.
Surgical treatment and functional outcome of bilateral symmetrical hip dislocation and Pipkin type II femoral head fracture: a 5-year follow-up case report and literature review
Authors: Shakya Sujan , Chen Jialei , Xing Fei , Xiang Zhou , Duan Xin
Published: April 2023

Background

Bilateral posterior hip dislocation and femoral head fracture are rare injuries, which may be the earliest case report that focuses on treatment with open reduction via the direct anterior approach (DAA) for bilateral symmetrical Pipkin type II fracture within 5 years of the follow-up period.

Case report

We present a case of bilateral posterior dislocation with a femoral head fracture (Pipkin II) of the hip in 47-year-old woman caused by a high-velocity accident. The dislocation was successfully reduced under general anesthesia at a local hospital and transferred to a tertiary center for surgical management. She was surgically treated with internal fixation using three Herbert screws on the bilateral hips. The DAA was used during surgery. Follow-up for 5 years was performed, and functional outcomes were evaluated using the D'Aubigné range of motion and modified Harris hip score. The range of motion in the bilateral hip was satisfactory, with no signs of post-traumatic arthritis, heterotopic ossification, or avascular necrosis of the femoral head.

Conclusion

Surgical management of bilateral Pipkin type II fractures was performed successfully with open reduction and internal fixation using a safe and reliable direct anterior approach, with good functional outcomes at 5-year follow-up.
Risk factors differ for viable and low viable crushed piglets in free farrowing pens
Authors: Spörri-Vontobel Cornelia , Simmler Michael , Wechsler Beat , Scriba Madeleine F.
Published: April 2023

Newborn piglets have a high risk of being crushed by the sow, and this risk implies welfare and economic consequences. The aim of this study was to investigate the importance of differentiating between low viable (secondary crushing losses) and viable crushed (primary crushing losses) piglets for the evaluation of risk factors for crushing related to characteristics of the sow, the litter, and the environment. Eleven Swiss farmers recorded sows’ production data (parity class, gestation length, numbers of live-born and stillborn piglets), data (age, sex, weight, cause of death, and signs of weakness) for every live-born piglet that died in the first week after birth (piglet loss), and ambient temperature. Piglet losses were assigned to five categorical events: piglet loss, subdivided into not crushed and crushed, the latter being further subdivided into low viable crushed and viable crushed. Piglets recorded by the farmer as crushed were assigned to the events low viable crushed and viable crushed based on the piglet’s body weight and signs of weakness (diseases, malformations). Data of 9,543 live-born piglets from 740 litters were eventually used to statistically model the hazard of dying at any given time in the first week after birth due to one of these events (mixed-effects Cox model). Five potential risk factors were analyzed as co-variates: parity class, gestation length, number of live-born piglets, number of stillborn piglets, and daily number of hours with ambient temperature >30°C. We identified two risk factors for dying from the event viable crushed that were not identified as risk factors for low viable crushed, namely shorter gestation length and higher daily number of hours with ambient temperature  > 30°C. Vice-versa, we identified additional live-born piglets in the litter as risk factor for low viable crushed, but not for viable crushed. Our results show the importance of differentiating between low viable and viable crushed piglets for the interpretation of risk factors for crushing losses. Therefore, we suggest that for breeding purposes and in research, this differentiation should be made.
Impact of Deferred Versus Continuous Sheep Grazing on Soil Compaction in the Mediterranean Montado Ecosystem
Authors: Serrano João , Carreira Emanuel , Shahidian Shakib , de Carvalho Mário , Marques da Silva José , Paniagua Luís Lorenzo , Moral Francisco , Pereira Alfredo
Published: April 2023

Deferred grazing (DG) consists in adapting the number of animals and the number of days grazed to the availability of pasture. Compared to continuous grazing (CG), which is based on a permanent and low stocking rate, DG is a management strategy that aims at optimizing the use of the resources available in the Mediterranean Montado ecosystem. This study with sheep grazing, carried out between 2019 and 2021 on a 4 ha pasture in Alentejo region of the Southern of Portugal, assesses the impact of these two grazing management systems on soil compaction as a result of animal trampling. This area of native natural grassland (a dryland pasture, mixture of grasses, legumes, and composite species) was divided into four grazing parks of 1 ha each, two under DG management and two under CG management. At the end of the study, the cone index (CI, in kPa) was measured in the topsoil layer (0–30 cm) with an electronic cone penetrometer at 48 georeferenced areas (12 in each park). The results of CI measurement showed no significant differences between treatments in all depths measured (0–10, 10–20, and 20–30 cm). These findings are encouraging from the point of view of soil conservation and sustainability, revealing good prospects for the intensification of extensive livestock production. Future work should evaluate the long-term impact and consider, at the same time, other ecosystem services and system productivity indicators.
Breeding Wheat for Powdery Mildew Resistance: Genetic Resources and Methodologies—A Review
Authors: Bapela Theresa , Shimelis Hussein , Terefe Tarekegn , Bourras Salim , Sánchez-Martín Javier , Douchkov Dimitar , Desiderio Francesca , Tsilo Toi John
Published: April 2023

Powdery mildew (PM) of wheat caused by Blumeria graminis f. sp. tritici is among the most important wheat diseases, causing significant yield and quality losses in many countries worldwide. Considerable progress has been made in resistance breeding to mitigate powdery mildew. Genetic host resistance employs either race-specific (qualitative) resistance, race-non-specific (quantitative), or a combination of both. Over recent decades, efforts to identify host resistance traits to powdery mildew have led to the discovery of over 240 genes and quantitative trait loci (QTLs) across all 21 wheat chromosomes. Sources of PM resistance in wheat include landraces, synthetic, cultivated, and wild species. The resistance identified in various genetic resources is transferred to the elite genetic background of a well-adapted cultivar with minimum linkage drag using advanced breeding and selection approaches. In this effort, wheat landraces have emerged as an important source of allelic and genetic diversity, which is highly valuable for developing new PM-resistant cultivars. However, most landraces have not been characterized for PM resistance, limiting their use in breeding programs. PM resistance is a polygenic trait; therefore, the degree of such resistance is mostly influenced by environmental conditions. Another challenge in breeding for PM resistance has been the lack of consistent disease pressure in multi-environment trials, which compromises phenotypic selection efficiency. It is therefore imperative to complement conventional breeding technologies with molecular breeding to improve selection efficiency. High-throughput genotyping techniques, based on chip array or sequencing, have increased the capacity to identify the genetic basis of PM resistance. However, developing PM-resistant cultivars is still challenging, and there is a need to harness the potential of new approaches to accelerate breeding progress. The main objective of this review is to describe the status of breeding for powdery mildew resistance, as well as the latest discoveries that offer novel ways to achieve durable PM resistance. Major topics discussed in the review include the genetic basis of PM resistance in wheat, available genetic resources for race-specific and adult-plant resistance to PM, important gene banks, and conventional and complimentary molecular breeding approaches, with an emphasis on marker-assisted selection (MAS).
The Production of Oxalate by Aspergillus niger under Different Lead Concentrations
Authors: Huang Yijun , Zhang Liangliang , Yuan Shijia , Liu Wenpei , Zhang Chaochun , Tian Da , Ye Xinxin
Published: April 2023

In this study, using a typical acid-producing fungi, Aspergillus niger (A. niger, CGMCC 23272), we investigated the capacity of organic acid production under different lead (Pb) concentrations. A. niger has a high Pb tolerance, which can maintain the growth of hypha at 1500 mg/L Pb concentration. Oxalic acid is the primary organic acid produced by A. niger. A. niger was shown to maintain the ability to produce oxalic acid under different Pb concentrations, which ranged from 522.8 to 1130.5 mg/L. The formed lead oxalate also confirmed the production of oxalic acid by A. niger. Meanwhile, the formation of lead oxalate minerals dominated the resistance of Pb toxicity by A. niger. More than 95% of Pb cations were removed by A. niger under different Pb concentrations. The high Pb toxicity (1500 mg/L) could stimulate pyruvate dehydrogenase enzyme activities, which increased from 0.05 to 0.13 nmol/min/g after three days of incubation. The low Pb toxicity (500 and 1000 mg/L) could improve the production of oxalic acid by A. niger. This indicates that the metabolism of organic acid by A. niger can be improved by a high Pb concentration via the tricarboxylic acid cycle.
A Cysteine-Reloading Process Initiating the Biosynthesis of the Bicyclic Scaffold of Dithiolopyrrolones
Authors: Chen Yan , Tu Yanqin , Pan Tingyu , Deng Zixin , Duan Lian
Published: April 2023

Dithiolopyrrolone antibiotics are well known for their outstanding biological activities, and their biosynthesis has been studied vigorously. However, the biosynthesis mechanism of the characteristic bicyclic scaffold is still unknown after years of research. To uncover this mechanism, a multi-domain non-ribosomal peptide synthase DtpB from the biosynthetic gene cluster of thiolutin was selected as an object to study. We discovered that its adenylation domain not only recognized and adenylated cysteine, but also played an essential role in the formation of the peptide bond. Notably, an eight-membered ring compound was also discovered as an intermediate during the formation of the bicyclic structure. Based on these findings, we propose a new mechanism for the biosynthesis of the bicyclic scaffold of dithiolopyrrolones, and unveil additional functions of the adenylation domain.
Using an Antibiogram Profile to Improve Infection Control and Rational Antimicrobial Therapy in an Urban Hospital in The Gambia, Strategies and Lessons for Low- and Middle-Income Countries
Authors: Darboe Saffiatou , Mirasol Ruel , Adejuyigbe Babapelumi , Muhammad Abdul Khalie , Nadjm Behzad , De St. Maurice Annabelle , Dogan Tiffany L. , Ceesay Buntung , Umukoro Solomon , Okomo Uduak , Nwakanma Davis , Roca Anna , Secka Ousman , Forrest Karen , Garner Omai B.
Published: April 2023

Antimicrobial resistance is a global health threat and efforts to mitigate it is warranted, thus the need for local antibiograms to improve stewardship. This study highlights the process that was used to develop an antibiogram to monitor resistance at a secondary-level health facility to aid empirical clinical decision making in a sub-Saharan African county. This retrospective cross-sectional descriptive study used 3 years of cumulative data from January 2016 to December 2018. Phenotypic data was manually imputed into WHONET and the cumulative antibiogram constructed using standardized methodologies according to CLSI M39-A4 guidelines. Pathogens were identified by standard manual microbiological methods and antimicrobial susceptibility testing was performed using Kirby-Bauer disc diffusion method according to CLSI M100 guidelines. A total of 14,776 non-duplicate samples were processed of which 1163 (7.9%) were positive for clinically significant pathogens. Among the 1163 pathogens, E. coli (n = 315) S. aureus (n = 232), and K. pneumoniae (n = 96) were the leading cause of disease. Overall, the susceptibility for E. coli and K. pneumoniae from all samples were: trimethoprim-sulfamethoxazole (17% and 28%), tetracycline (26% and 33%), gentamicin (72% and 46%), chloramphenicol (76 and 60%), and ciprofloxacin (69% and 59%), and amoxicillin/clavulanic (77% and 54%) respectively. Extended spectrum beta-lactamase (ESBL) resistance was present in 23% (71/315) vs. 35% (34/96) respectively. S. aureus susceptibility for methicillin was 99%. This antibiogram has shown that improvement in combination therapy is warranted in The Gambia.
The National Implementation of a Community Pharmacy Antimicrobial Stewardship Intervention (PAMSI) through the English Pharmacy Quality Scheme 2020 to 2022
Authors: Hayes Catherine V. , Parekh Sejal , Lecky Donna M. , Loader Jill , Triggs-Hodge Carry , Ashiru-Oredope Diane
Published: April 2023

Since 2020, England’s Pharmacy Quality Scheme (PQS) has incentivised increased antimicrobial stewardship (AMS) activities in community pharmacy. In 2020/21, this included the requirement for staff to complete an AMS e-Learning module, pledge to be an Antibiotic Guardian and develop an AMS Action plan. To build and embed these initiatives, in 2021/22, the PQS required the use of the TARGET Antibiotic Checklist (an AMS tool for use when patients present with a prescription for antibiotics to support conducting and recording of a series of safety and appropriateness checks against each prescribed antibiotic). This paper describes the implementation of the national PQS criteria from 2020 to 2022, and details community pharmacies’ AMS activities and barriers to implementation of the 2021/22 criteria. A total of 8374 community pharmacies submitted data collected using the TARGET Antibiotic Checklist for 213,105 prescriptions; 44% surpassed the required number for the PQS. Pharmacy teams reported checking the following: duration, dose, and appropriateness of antibiotics; patient allergies and medicine interactions (94–95%); antibiotic prescribing guideline adherence (89%); and the patient’s previous use of antibiotics (81%). The prescriber was contacted for 1.3% of TARGET Antibiotic Checklists (2741), and the most common reasons for such contacts were related to dose, duration, and possible patient allergy. A total of 105 pharmacy staff responded to a follow-up questionnaire, which suggested that some AMS principles had been embedded into daily practice; however, the necessary time commitment was a barrier. The PQS was able to incentivise mass AMS activities at pace over consecutive years for England’s community pharmacies simultaneously. Future research should monitor the continuation of activities and the wider impacts on primary care.
Mitochondria-Targeted Antioxidants as a Therapeutic Strategy for Chronic Obstructive Pulmonary Disease
Authors: Fairley Lauren H. , Das Shatarupa , Dharwal Vivek , Amorim Nadia , Hegarty Karl J. , Wadhwa Ridhima , Mounika Guntipally , Hansbro Philip M.
Published: April 2023

Oxidative stress is a major hallmark of COPD, contributing to inflammatory signaling, corticosteroid resistance, DNA damage, and accelerated lung aging and cellular senescence. Evidence suggests that oxidative damage is not solely due to exogenous exposure to inhaled irritants, but also endogenous sources of oxidants in the form of reactive oxygen species (ROS). Mitochondria, the major producers of ROS, exhibit impaired structure and function in COPD, resulting in reduced oxidative capacity and excessive ROS production. Antioxidants have been shown to protect against ROS-induced oxidative damage in COPD, by reducing ROS levels, reducing inflammation, and protecting against the development of emphysema. However, currently available antioxidants are not routinely used in the management of COPD, suggesting the need for more effective antioxidant agents. In recent years, a number of mitochondria-targeted antioxidant (MTA) compounds have been developed that are capable of crossing the mitochondria lipid bilayer, offering a more targeted approach to reducing ROS at its source. In particular, MTAs have been shown to illicit greater protective effects compared to non-targeted, cellular antioxidants by further reducing apoptosis and offering greater protection against mtDNA damage, suggesting they are promising therapeutic agents for the treatment of COPD. Here, we review evidence for the therapeutic potential of MTAs as a treatment for chronic lung disease and discuss current challenges and future directions.