bluuebunny/crossref_metadata_2025 huggingface dataset:
The use of autogenous tooth bone graft is an efficient method of alveolar ridge preservation – meta-analysis and systematic review
Authors: Solyom Eleonora , Szalai Eszter , Czumbel Márk László , Szabo Bence , Váncsa Szilárd , Mikulas Krisztina , Radoczy-Drajko Zsombor , Varga Gabor , Hegyi Péter , Molnar Balint , Fazekas Reka
Published: April 2023

Background

Ridge resorption following tooth extraction may be reduced by alveolar ridge preservation (ARP). Previous randomized clinical trials and systematic reviews have suggested that autogenous tooth bone graft (ATB) can be an effective alternative material for ARP. However, the results are heterogeneous. Therefore, our research aimed to evaluate the efficacy of ATB in ARP.

Methods

A systematic search was conducted in Cochrane Library, Embase, MEDLINE and Scopus for studies published from inception to 31 November 2021. We searched searched for randomized, non-randomized controlled trials and case series reporting on ATB use for ARP. The primary outcome was the ridge width difference pre- and post-surgery, measured in millimetres (mm) measured on CBCT (cone beam computed tomography). The secondary outcomes were the histological results. We followed the PRISMA2020 recommendations for reporting our systematic review and meta-analysis.

Results

The analysis included eight studies for the primary and six for the secondary outcomes. The meta-analysis revealed a positive ridge preservation effect with a pooled mean difference ridge width change of -0.72 mm. The pooled mean residual graft proportion was 11.61%, and the newly formed bone proportion was 40.23%. The pooled mean of newly formed bone proportion was higher in the group where ATB originated from both the root and crown of the tooth.

Conclusions

ATB is an effective particulate graft material in ARP. Complete demineralization of the ATB tends to decrease the proportion of newly formed bone. ATB can be an attractive option for ARP.

Trial registration

The study protocol was registered on PROSPERO (CRD42021287890).
The need for non-technical skills education in orthopedic surgery
Authors: Alzahrani Khalid H. , Abutalib Raid A. , Elsheikh Ahmed M. , Alzahrani Laura K. , Khoshhal Khalid I.
Published: April 2023

Background

The issue of surgical safety has increased significantly over the last few decades. Several studies have established that it is linked to non-technical performance, rather than clinical competencies. Non-technical skills can be blended with technical training in the surgical profession to improve surgeons’ abilities and enhance patient care and procedural skills. The main goal of this study was to determine orthopedic surgeons’ requirements of non-technical skills, and to identify the most pressing issues.

Methods

We conducted a self-administered online questionnaire survey in this cross-sectional study. The questionnaire was piloted, validated, pretested, and clearly stated the study’s purpose. After the pilot, minor wording and questions were clarified before starting the data collection. Orthopedic surgeons from the Middle East and Northern Africa were invited. The questionnaire was based on a five-point Likert scale, the data were analyzed categorically, and variables were summarized as descriptive statistics.

Results

Of the 1713 orthopedic surgeons invited, 60% completed the survey (1033 out of 1713). The majority demonstrated a high likelihood of participating in such activities in the future (80.5%). More than half (53%) of them preferred non-technical skills courses to be part of major orthopedic conferences, rather than independent courses. Most (65%) chose them to be face-to-face. Although 97.2% agreed on the importance of these courses, only 27% had attended similar courses in the last three years. Patient safety, infection prevention and control, and communication skills were ranked at the top as topics to be addressed. Moreover, participants indicated they would most likely attend courses on infection prevention and control, patient safety and teamwork, and team management.

Conclusion

The results highlight the need for non-technical skills training in the region and the general preferences regarding modality and setting. These findings support the high demand from orthopedic surgeons’ perspective to develop an educational program on non-technical skills.
Effectiveness of implementing of an infection control link nurse program to improve compliance with standard precautions and hand hygiene among nurses: a quasi-experimental study
Authors: Ghorbanmovahhed Shamsi , Shahbazi Shahla , Gilani Neda , Ostadi Ali , Shabanloei Reza , Gholizadeh Leila
Published: April 2023

Background

Standard precautions (SPs) including hand hygiene are considered fundamental protective measures to manage health care-associated infections (HCAIs) and to reduce occupational health hazards. The purpose of this research was to examine the effectiveness of an infection control link nurse (ICLN) program on compliance with SPs and hand hygiene among nurses.

Methods

A quasi-experimental study with a pretest-post-test design was conducted with participating of 154 clinical nurses who worked in different wards of a tertiary referral teaching hospital in Iran. The intervention group (n = 77) had 16 infection control link nurses nominated. The control group (n = 77) received only the standard multimodal approach used in the hospital. Pre- and post-test assessment of compliance with standard precautions and hand hygiene compliance was performed via the Compliance with Standard Precautions Scale (CSPS) and the World Health Organization observational hand hygiene form. Two independent sample t-tests were used to examine differences between Compliance with Standard Precautions and hand hygiene Compliance among nurses in intervention and control group. Multiple linear regression analysis was used to assess the effect size.

Results

After developing and implementing the infection control link nurse program, no statistically significant improvement was found in the Compliance with Standard Precautions (β = 5.18; 95% CI= -0.3–10.65, p = 0.064). An improvement in hand hygiene compliance was observed among nurses in the intervention group that improved statistically significant from 18.80% before the program to 37.32% 6 months after the program (β = 20.82; 95% CI 16.40–25.25, p < 0.001).

Conclusions

Given the continuing level of interest that exists in improving health care workers’ hand hygiene practices, the findings of this study provide significant practical implications for hospitals seeking to improve compliance with hand hygiene among nurses, showing the effectiveness of using infection control link nurse program. Further research is needed to assess effectiveness of using infection control link nurse program to improve compliance with standard precautions.
Faculty development strategies to empower university teachers by their educational role: A qualitative study on the faculty members and students’ experiences at Iranian universities of medical sciences
Authors: Ghasemi Sima , Bazrafkan Leila , Shojaei Arash , Rakhshani Tayebeh , Shokrpour Nasrin
Published: April 2023

Background

This study aimed to identify and explain the strategies of faculty development based on their role at Iranian Universities of Medical Sciences.

Methods

We conducted a qualitative content analysis study in 2021 using purposive, snowball sampling, with a maximum variation in the faculty members’ age and experience level. Twenty four participants were enrolled in this study (eighteen faculty members and six medical sciences students); data collection consisted of two phases of semi-structured interviews and a brainstorming group technique. Data were categorized into two themes and six related subthemes, based on their similarities and differences after frequent summarization.

Results

The data analysis yielded two themes and eight categories. The first theme was to explain competencies based on role and task with two sub-themes: Tasks and capabilities and development and excellence of personal qualities. The second theme was the best strategies for empowering the teachers with four sub-themes, including problem-based learning, integration of methods, evaluation-based education, and scholarship in education (PIES), which explains the strategies that can support the development of teachers in medical sciences universities, and all the concepts were interrelated to each other.

Conclusion

From the experiences of faculty members, the importance of some strategies in education and empowering the teachers’ professional competence dimensions should be emphasized. PIES could explain the practical strategies that can support the development of teachers in medical sciences universities.
Patient-centered care and geriatric knowledge translation among healthcare providers in Vietnam: translation and validation of the patient-centered care measure
Authors: Adetunji Oluwarantimi , Bishai David , Pham Cuong Viet , Taylor Janiece , Thi Ngan Tran , Khan Zainab , Bachani Abdulgafoor M.
Published: April 2023

Background

People are living longer, and the majority of aging people reside in low- and middle-income countries (LMICs). However, inappropriate healthcare contributes to health disparities between populations of aging people and leads to care dependency and social isolation. Tools to assess and evaluate the effectiveness of quality improvement interventions for geriatric care in LMICs are limited. The aim of this study was to provide a validated and culturally relevant instrument to assess patient-centered care in Vietnam, where the population of aging people is growing rapidly.

Methods

The Patient-Centered Care (PCC) measure was translated from English to Vietnamese using forward-backward method. The PCC measure grouped activities into sub-domains of holistic, collaborative, and responsive care. A bilingual expert panel rated the cross-cultural relevance and translation equivalence of the instrument. We calculated Content Validity Indexing (CVI) scores at both the item (I-CVI) and scale (S-CVI/Ave) levels to evaluate the relevance of the Vietnamese PCC (VPCC) measure to geriatric care in the Vietnamese context. We piloted the translated instrument VPCC measure with 112 healthcare providers in Hanoi, Vietnam. Multiple logistic regression models were specified to test the a priori null hypothesis that geriatric knowledge is not different among healthcare providers with perception of high implementation compared with low implementation of PCC measures.

Results

On the item level, all 20 questions had excellent validity ratings. The VPCC had excellent content validity (S-CVI/Ave of 0.96) and translation equivalence (TS- CVI/Ave of 0.94). In the pilot study, the highest-rated PCC elements were the holistic provision of information and collaborative care, while the lowest-rated elements were the holistic attendance to patients’ needs and responsive care. Attention to the psychosocial needs of aging people and poor coordination of care within and beyond the health system were the lowest-rated PCC activities. After controlling for healthcare provider characteristics, the odds of the perception of high implementation of collaborative care were increased by 21% for each increase in geriatric knowledge score. We fail to reject the null hypotheses for holistic care, responsive care and PCC.

Conclusion

The VPCC is a validated instrument that may be utilized to systemically evaluate the practice of patient-centered geriatric care in Vietnam.
Ear and hearing care programs for First Nations children: a scoping review
Authors: Nash Kai , Macniven Rona , Clague Liesa , Coates Harvey , Fitzpatrick Mark , Gunasekera Hasantha , Gwynne Kylie , Halvorsen Luke , Harkus Samantha , Holt Leanne , Lumby Noeleen , Neal Katie , Orr Neil , Pellicano Elizabeth , Rambaldini Boe , McMahon Catherine
Published: April 2023

Background

Ear and hearing care programs are critical to early detection and management of otitis media (or middle ear disease). Otitis media and associated hearing loss disproportionately impacts First Nations children. This affects speech and language development, social and cognitive development and, in turn, education and life outcomes. This scoping review aimed to better understand how ear and hearing care programs for First Nations children in high-income colonial-settler countries aimed to reduce the burden of otitis media and increase equitable access to care. Specifically, the review aimed to chart program strategies, map the focus of each program against 4 parts of a care pathway (prevention, detection, diagnosis/management, rehabilitation), and to identify the factors that indicated the longer-term sustainability and success of programs.

Method

A database search was conducted in March 2021 using Medline, Embase, Global Health, APA PsycInfo, CINAHL, Web of Science Core Collection, Scopus, and Academic Search Premier. Programs were eligible or inclusion if they had either been developed or run at any time between January 2010 to March 2021. Search terms encompassed terms such as First Nations children, ear and hearing care, and health programs, initiatives, campaigns, and services.

Results

Twenty-seven articles met the criteria to be included in the review and described a total of twenty-one ear and hearing care programs. Programs employed strategies to: (i) connect patients to specialist services, (ii) improve cultural safety of services, and (iii) increase access to ear and hearing care services. However, program evaluation measures were limited to outputs or the evaluation of service-level outcome, rather than patient-based outcomes. Factors which contributed to program sustainability included funding and community involvement although these were limited in many cases.

Conclusion

The result of this study highlighted that programs primarily operate at two points along the care pathway—detection and diagnosis/management, presumably where the greatest need lies. Targeted strategies were used to address these, some which were limited in their approach. The success of many programs are evaluated as outputs, and many programs rely on funding sources which can potentially limit longer-term sustainability. Finally, the involvement of First Nations people and communities typically only occurred during implementation rather than across the development of the program. Future programs should be embedded within a connected system of care and tied to existing policies and funding streams to ensure long term viability. Programs should be governed and evaluated by First Nations communities to further ensure programs are sustainable and are designed to meet community needs.
“Quality teaches you how to use water. It doesn’t provide a water pump”: a qualitative study of context and mechanisms of action in an Ethiopian quality improvement program
Authors: Procureur F , Estifanos AS , Keraga DW , Kiflie Alemayehu AK , Hailemariam NW , Schellenberg J , Magge H , Hill Z
Published: April 2023

Background

Quality improvement collaboratives are a common approach to bridging the quality-of-care gap, but little is known about implementation in low-income settings. Implementers rarely consider mechanisms of change or the role of context, which may explain collaboratives’ varied impacts.

Methods

To understand mechanisms and contextual influences we conducted 55 in-depth interviews with staff from four health centres and two hospitals involved in quality improvement collaboratives in Ethiopia. We also generated control charts for selected indicators to explore any impacts of the collaboratives.

Results

The cross facility learning sessions increased the prominence and focus on quality, allowed learning from experts and peers and were motivational through public recognition of success or a desire to emulate peers. Within facilities, new structures and processes were created. These were fragile and sometimes alienating to those outside the improvement team. The trusted and respected mentors were important for support, motivation and accountability. Where mentor visits were infrequent or mentors less skilled, team function was impacted. These mechanisms were more prominent, and quality improvement more functional, in facilities with strong leadership and pre-existing good teamwork; as staff had shared goals, an active approach to problems and were more willing and able to be flexible to implement change ideas. Quality improvement structures and processes were more likely to be internally driven and knowledge transferred to other staff in these facilities, which reduced the impact of staff turnover and increased buy-in. In facilities which lacked essential inputs, staff struggled to see how the collaborative could meaningfully improve quality and were less likely to have functioning quality improvement. The unexpected civil unrest in one region strongly disrupted the health system and the collaborative. These contextual issues were fluid, with multiple interactions and linkages.

Conclusions

The study confirms the need to carefully consider context in the implementation of quality improvement collaboratives. Facilities that implement quality improvement successfully may be those that already have characteristics that foster quality. Quality improvement may be alienating to those outside of the improvement team and implementers should not assume the organic spread or transfer of quality improvement knowledge.
Hibberdia magna (Chrysophyceae): a promising freshwater fucoxanthin and polyunsaturated fatty acid producer
Authors: Střížek Antonín , Přibyl Pavel , Lukeš Martin , Grivalský Tomáš , Kopecký Jiří , Galica Tomáš , Hrouzek Pavel
Published: April 2023

Background

Algae are prominent producers of carotenoids and polyunsaturated fatty acids which are greatly prized in the food and pharmaceutic industry. Fucoxanthin represents a notable high-value carotenoid produced exclusively by algae. Its benefits range far beyond just antioxidant activity and include cancer prevention, anti-diabetes, anti-obesity, and many other positive effects. Accordingly, large-scale microalgae cultivation to produce fucoxanthin and polyunsaturated fatty acids is still under intensive development in the commercial and academic sectors. Industrially exploitable strains are predominantly derived from marine species while comparable freshwater fucoxanthin producers have yet to be explored.

Results

In this study, we searched for freshwater fucoxanthin producers among photoautotrophic flagellates including members of the class Chrysophyceae. The initial screening turned our attention to the chrysophyte alga Hibberdia magna. We performed a comprehensive cultivation experiments using a temperature × light cross-gradient to assess the impact of these conditions on the target compounds productivity. Here we present the observations that H. magna simultaneously produces fucoxanthin (max. 1.2% dry biomass) and polyunsaturated fatty acids (max. ~ 9.9% dry biomass) and is accessible to routine cultivation in lab-scale conditions. The highest biomass yields were 3.73 g L−1 accompanied by maximal volumetric productivity of 0.54 g L−1 d−1 which are comparable values to marine microalgae fucoxanthin producers in phototrophic mode. H. magna demonstrated different optimal conditions for biomass, fucoxanthin, and fatty acid accumulation. While maximal fucoxanthin productivities were obtained in dim light and moderate temperatures (23 °C× 80 µmol m−2 s−1), the highest PUFA and overall biomass productivities were found in low temperature and high light (17–20 °C × 320–480 µmol m−2 s−1). Thus, a smart biotechnology setup should be designed to fully utilize H. magna biotechnological potential.

Conclusions

Our research brings pioneer insight into the biotechnology potential of freshwater autotrophic flagellates and highlights their ability to produce high-value compounds. Freshwater fucoxanthin-producing species are of special importance as the use of sea-water-based media may increase cultivation costs and prohibits inland microalgae production.
The benefits and risks of nostalgia: analysis of a fictional case with special reference to ethical and existential issues
Authors: Bäckryd Emmanuel
Published: April 2023

Background

In a previous paper in Philos Ethics Humanit Med, the 1937 Swedish novel Sömnlös (Swedish for sleepless) by Vilhelm Moberg was used as background for a thought experiment, in which last century’s progresses concerning the safety of sleeping pills were projected into the future. This gave rise to a theoretical discussion about broad medico-philosophical questions such as (among other things) the concept of pharmaceuticalisation.

Methods

In this follow-up paper, the theme of insomnia in Sömnlös is complemented by a discussion of the concept of nostalgia. The core of the paper is a theoretical discussion about the benefits and risks of nostalgia, bringing together some aspects of recent psychological research about the construct of nostalgia with the main story line of the novel.

Results and Conclusion

Nostalgia is portrayed as being, in some sense at least, ultimately beneficial for the protagonist of Sömnlös. This is congruent with recent psychological research. However, the story also shows that nostalgia may lead to problematic behaviours, at least when viewed from a virtue ethics perspective. Hence, nostalgia is both what leads the protagonist into ethically problematic behaviour and that which (paradoxically) ultimately saves him from his initial lack of courage, justice, temperance and practical wisdom. Moreover, the protagonist does not only “grow” ethically but also existentially. Hence, the novel opens up the possibility that insomnia and nostalgia might be viewed as bearers of important existential information (cf. sociologist of religion Peter L. Berger and his concept of “signals of transcendence”).
Prognostic factors in radiotherapy of anaplastic thyroid carcinoma: a single center study over 31 years
Authors: Jacob Julia , Vordermark Dirk , Lorenz Kerstin , Medenwald Daniel
Published: April 2023

Background

Anaplastic thyroid carcinoma has a very poor prognosis. We analyzed the effect of surgery, radiotherapy and chemotherapy on survival time and side effects in patients with ATC.

Methods

We retrospectively analyzed all patients (n = 63) with histologically confirmed ATC who presented at our clinic between 1989 and 2020. We analyzed the survival with Kaplan–Meier curves and cox proportional hazard models and acute toxicities with logistic regression models.

Results

Out of 63 patients, 62 received radiotherapy, 74% underwent surgery and 24% received combined chemotherapy. A median radiation dose of 49 Gy (range 4–66 Gy) was applied. In 32% of the cases opposing-field technique was used, in 18% 3D-conformal, in 27% a combination of opposing field and 3D-conformal technique and 21% obtained IMRT (intensity modulated radiotherapy) or VMAT (volumetric modulated arc radiotherapy). Median overall survival (OS) was 6 months. We identified five predictive factors relevant for survival: absence of distant metastases at the time of diagnosis (OS 8 months), surgery (OS 9.8 months), resection status R0 (OS 14 months), radiation dose of 50 Gy or higher (OS 13 months) and multimodal therapy (surgery, radiotherapy and chemotherapy) with a median OS of 9.7 months.

Conclusion

In spite of the dismal outcome, longer survival can be achieved in some patients with ATC using surgery and radiotherapy with a high radiation dose. Compared to our previous study, there are no significant advantages in overall survival.

Trial registration Retrospectively registered.
Randomized controlled trial data for successful new drug application for rare diseases in the United States
Authors: Kubota Yosuke , Narukawa Mamoru
Published: April 2023

Background

Randomized controlled trial (RCT) data have important implications in drug development. However, the feasibility and cost of conducting RCTs lower the motivation for drug development, especially for rare diseases. We investigated the potential factors associated with the need for RCTs in the clinical data package for new drug applications for rare diseases in the United States (US). This study focused on 233 drugs with orphan drug designations approved in the US between April 2001 and March 2021. Univariable and multivariable logistic regression analyses were conducted to investigate the association between the presence or absence of RCTs in the clinical data package for new drug applications.

Results

Multivariable logistic regression analysis showed that the severity of the disease outcome (odds ratio [OR] 5.63, 95% confidence interval [CI] 2.64–12.00), type of drug usage (odds ratio [OR] 2.95, 95% confidence interval [CI] 1.80–18.57), and type of primary endpoint (OR 5.57, 95% CI 2.57–12.06) were associated with the presence or absence of RCTs.

Conclusions

Our results indicated that the presence or absence of RCT data in the clinical data package for successful new drug application in the US was associated with three factors: severity of disease outcome, type of drug usage, and type of primary endpoint. These results highlight the importance of selecting target diseases and potential efficacy variables to optimize orphan drug development.
Pharmacological induction of membrane lipid poly-unsaturation sensitizes melanoma to ROS inducers and overcomes acquired resistance to targeted therapy
Authors: Talebi Ali , de Laat Vincent , Spotbeen Xander , Dehairs Jonas , Rambow Florian , Rogiers Aljosja , Vanderhoydonc Frank , Rizotto Lara , Planque Mélanie , Doglioni Ginevra , Motamedi Sahar , Nittner David , Roskams Tania , Agostinis Patrizia , Bechter Oliver , Boecxstaens Veerle , Garmyn Marjan , O’Farrell Marie , Wagman Alan , Kemble George , Leucci Eleonora , Fendt Sarah-Maria , Marine Jean-Christophe , Swinnen Johannes V.
Published: April 2023

Background

One of the key limitations of targeted cancer therapies is the rapid onset of therapy resistance. Taking BRAF-mutant melanoma as paradigm, we previously identified the lipogenic regulator SREBP-1 as a central mediator of resistance to MAPK-targeted therapy. Reasoning that lipogenesis-mediated alterations in membrane lipid poly-unsaturation lie at the basis of therapy resistance, we targeted fatty acid synthase (FASN) as key player in this pathway to evoke an exquisite vulnerability to clinical inducers of reactive oxygen species (ROS), thereby rationalizing a novel clinically actionable combination therapy to overcome therapy resistance.

Methods

Using gene expression analysis and mass spectrometry-based lipidomics of BRAF-mutant melanoma cell lines, melanoma PDX and clinical data sets, we explored the association of FASN expression with membrane lipid poly-unsaturation and therapy-resistance. Next, we treated therapy-resistant models with a preclinical FASN inhibitor TVB-3664 and a panel of ROS inducers and performed ROS analysis, lipid peroxidation tests and real-time cell proliferation assays. Finally, we explored the combination of MAPK inhibitors, TVB-3664 and arsenic trioxide (ATO, as a clinically used ROS-inducer) in Mel006 BRAF mutant PDX as a gold model of therapy resistance and assessed the effect on tumor growth, survival and systemic toxicity.

Results

We found that FASN expression is consistently increased upon the onset of therapy resistance in clinical melanoma samples, in cell lines and in Mel006 PDX and is associated with decreased lipid poly-unsaturation. Forcing lipid poly-unsaturation in therapy-resistant models by combining MAPK inhibition with FASN inhibition attenuated cell proliferation and rendered cells exquisitely sensitive to a host of ROS inducers. In particular, the triple combination of MAPK inhibition, FASN inhibition, and the clinical ROS-inducing compound ATO dramatically increased survival of Mel006 PDX models from 15 to 72% with no associated signs of toxicity.

Conclusions

We conclude that under MAPK inhibition the direct pharmacological inhibition of FASN evokes an exquisite vulnerability to inducers of ROS by increasing membrane lipid poly-unsaturation. The exploitation of this vulnerability by combining MAPK and/or FASN inhibitors with inducers of ROS greatly delays the onset of therapy resistance and increases survival. Our work identifies a clinically actionable combinatorial treatment for therapy-resistant cancer.
Investigating the role of AA9 LPMOs in enzymatic hydrolysis of differentially steam-pretreated spruce
Authors: Caputo Fabio , Tõlgo Monika , Naidjonoka Polina , Krogh Kristian B. R. M. , Novy Vera , Olsson Lisbeth
Published: April 2023

Background

To realize the full potential of softwood-based forest biorefineries, the bottlenecks of enzymatic saccharification of softwood need to be better understood. Here, we investigated the potential of lytic polysaccharide monooxygenases (LPMO9s) in softwood saccharification. Norway spruce was steam-pretreated at three different severities, leading to varying hemicellulose retention, lignin condensation, and cellulose ultrastructure. Hydrolyzability of the three substrates was assessed after pretreatment and after an additional knife-milling step, comparing the efficiency of cellulolytic Celluclast + Novozym 188 and LPMO-containing Cellic CTec2 cocktails. The role of Thermoascus aurantiacus TaLPMO9 in saccharification was assessed through time-course analysis of sugar release and accumulation of oxidized sugars, as well as wide-angle X-ray scattering analysis of cellulose ultrastructural changes.

Results

Glucose yield was 6% (w/w) with the mildest pretreatment (steam pretreatment at 210 °C without catalyst) and 66% (w/w) with the harshest (steam pretreatment at 210 °C with 3%(w/w) SO2) when using Celluclast + Novozym 188. Surprisingly, the yield was lower with all substrates when Cellic CTec2 was used. Therefore, the conditions for optimal LPMO activity were tested and it was found that enough O2 was present over the headspace and that the reducing power of the lignin of all three substrates was sufficient for the LPMOs in Cellic CTec2 to be active. Supplementation of Celluclast + Novozym 188 with TaLPMO9 increased the conversion of glucan by 1.6-fold and xylan by 1.5-fold, which was evident primarily in the later stages of saccharification (24–72 h). Improved glucan conversion could be explained by drastically reduced cellulose crystallinity of spruce substrates upon TaLPMO9 supplementation.

Conclusion

Our study demonstrated that LPMO addition to hydrolytic enzymes improves the release of glucose and xylose from steam-pretreated softwood substrates. Furthermore, softwood lignin provides enough reducing power for LPMOs, irrespective of pretreatment severity. These results provided new insights into the potential role of LPMOs in saccharification of industrially relevant softwood substrates.
Association of 410L, 1016I and 1534C kdr mutations with pyrethroid resistance in Aedes aegypti from Ouagadougou, Burkina Faso, and development of a one-step multiplex PCR method for the simultaneous detection of 1534C and 1016I kdr mutations
Authors: Sombié Aboubacar , Ouédraogo Wendegoudi Mathias , Oté Manabu , Saiki Erisha , Sakurai Tatsuya , Yaméogo Félix , Sanon Antoine , McCall Philip J. , Kanuka Hirotaka , Weetman David , Badolo Athanase
Published: April 2023

Background

Since 2000, Burkina Faso has experienced regular dengue cases and outbreaks, making dengue an increasingly important health concern for the country. Previous studies in Burkina Faso reported that resistance of Aedes aegypti to pyrethroid insecticides was associated with the F1534C and V1016I kdr mutations. The current study reports high resistance of Ae. aegypti populations to pyrethroid insecticides, likely supported by mutations in the voltage-gated sodium channel, here evidenced by genotyping the kdr SNPs V410L, V1016I and F1534C. We also describe a new multiplex PCR-based diagnostic of F1534C and V1016I kdr SNPs.

Methods

Larvae of Ae. aegypti were collected from three health districts of Ouagadougou in 2018. The resistance status of Ae. aegypti to permethrin (15 μg/ml) and deltamethrin (10 μg/ml) was tested using bottles and to malathion (5%) using WHO tube tests. All bioassays used 1-h exposure and mortality recorded 24 h post-exposure. Bioassay results were interpreted according to WHO thresholds for resistance diagnosis. The kdr mutations were screened using AS-PCR and TaqMan methods in exposed and non-exposed Aedes mosquitoes.

Results

Females from all health districts were resistant to permethrin and deltamethrin (< 20% mortality) but were fully susceptible to 5% malathion. The F1534C and V1016I kdr mutations were successfully detected using a newly developed multiplex PCR in perfect agreement with TaqMan method. The 1534C/1016I/410L haplotype was correlated with permethrin resistance but not with deltamethrin resistance; however, the test power was limited by a low frequency of dead individuals in deltamethrin exposure.

Conclusions

Resistance to pyrethroid insecticides is associated with kdr mutant haplotypes, while the absence of substantial resistance to malathion suggests that it remains a viable option for dengue vector control in Ouagadougou.
Identification of gametocyte-associated pir genes in the rodent malaria parasite, Plasmodium chabaudi chabaudi AS
Authors: Cunningham Deirdre A. , Reid Adam J. , Hosking Caroline , Deroost Katrien , Tumwine-Downey Irene , Sanders Mandy , Langhorne Jean
Published: April 2023

Objective

To analyse the transcriptional profiles of the pir multigene family of Plasmodium chabaudi chabaudi in male and female gametocytes isolated from the blood of infected mice.

Results

Infected red blood cells containing female and male P. chabaudi gametocytes transcribe a distinct set of genes encoded by the multigene family pir. The overall patterns are similar to what has been observed in the close relative P. berghei, but here we show that gametocyte-associated pir genes are distinct from those involved in chronic blood-stage infection and highlight a male-associated pir gene which should be the focus of future studies.
The embryology, metamorphosis, and muscle development of Schizocardium karankawa sp. nov. (Enteropneusta) from the Gulf of Mexico
Authors: Jabr Noura , Gonzalez Paul , Kocot Kevin M. , Cameron Christopher B.
Published: April 2023

Schizocardium karankawa sp. nov. has been collected from subtidal muds of the Laguna Madre, Texas, and the Mississippi coast, Gulf of Mexico. The Texas population is reproductive from early February to mid-April. Gametes are liberated by a small incision in a gonad. Oocyte germinal vesicle breakdown is increased in the presence of sperm, and the highest fertilization success was in the artificial seawater Jamarin U. Manually dechorionated embryos develop normally. Development was asynchronous via a tornaria larva, metamorphosis and maintained to the juvenile worm 6 gill-pore stage. Phalloidin-labeled late-stage tornaria revealed retractor muscles that connect the pericardial sac with the apical tuft anteriorly, the oesophagus ventrally, and muscle cells of the early mesocoels. The muscle development of early juvenile worms began with dorso-lateral trunk muscles, lateral trunk bands, and sphincters around the gill pores and anus. Adult worms are characterized by a stomochord that bifurcates anteriorly into paired vermiform processes, gill bars that extend almost the entire dorsal to ventral branchial region resulting in a narrow ventral hypobranchial ridge, and an elaborate epibranchial organ with six zones of discrete cell types. The trunk has up to three rows of liver sacs, and lateral gonads. The acorn worm evo-devo model species Saccoglossus kowalevskii, Ptychodera flava, and Schizocardium californicum are phylogenetically distant with disparate life histories. S. karnakawa from S. californicum are phylogenetically close, and differences between them that become apparent as adult worms include the number of gill pores and hepatic sacs, and elaborations of the heart–kidney–stomochord complex. An important challenge for evolutionary developmental biology is to form links from phylogenetically distant and large-scale differences to phylogenetically close and small-scale differences. This description of the embryology, development, and adult morphology of S. karankawa permits investigations into how acorn worm development evolves at fine scales.
Silencing NTPDase3 activity rehabilitates the osteogenic commitment of post-menopausal stem cell bone progenitors
Authors: Noronha-Matos José Bernardo , Pinto-Cardoso Rui , Bessa-Andrês Catarina , Magalhães-Cardoso Maria Teresa , Ferreirinha Fátima , Costa Maria Adelina , Marinhas José , Freitas Rolando , Lemos Rui , Vilaça Adélio , Oliveira António , Pelletier Julie , Sévigny Jean , Correia-de-Sá Paulo
Published: April 2023

Background

Endogenously released adenine and uracil nucleotides favour the osteogenic commitment of bone marrow-derived mesenchymal stromal cells (BM-MSCs) through the activation of ATP-sensitive P2X7 and UDP-sensitive P2Y6 receptors. Yet, these nucleotides have their osteogenic potential compromised in post-menopausal (Pm) women due to overexpression of nucleotide metabolizing enzymes, namely NTPDase3. This prompted us to investigate whether NTPDase3 gene silencing or inhibition of its enzymatic activity could rehabilitate the osteogenic potential of Pm BM-MSCs.

Methods

MSCs were harvested from the bone marrow of Pm women (69 ± 2 years old) and younger female controls (22 ± 4 years old). The cells were allowed to grow for 35 days in an osteogenic-inducing medium in either the absence or the presence of NTPDase3 inhibitors (PSB 06126 and hN3-B3s antibody); pre-treatment with a lentiviral short hairpin RNA (Lenti-shRNA) was used to silence the NTPDase3 gene expression. Immunofluorescence confocal microscopy was used to monitor protein cell densities. The osteogenic commitment of BM-MSCs was assessed by increases in the alkaline phosphatase (ALP) activity. The amount of the osteogenic transcription factor Osterix and the alizarin red-stained bone nodule formation. ATP was measured with the luciferin-luciferase bioluminescence assay. The kinetics of the extracellular ATP (100 µM) and UDP (100 µM) catabolism was assessed by HPLC

Results

The extracellular catabolism of ATP and UDP was faster in BM-MSCs from Pm women compared to younger females. The immunoreactivity against NTPDase3 increased 5.6-fold in BM-MSCs from Pm women vs. younger females. Selective inhibition or transient NTPDase3 gene silencing increased the extracellular accumulation of adenine and uracil nucleotides in cultured Pm BM-MSCs. Downregulation of NTPDase3 expression or activity rehabilitated the osteogenic commitment of Pm BM-MSCs measured as increases in ALP activity, Osterix protein cellular content and bone nodule formation; blockage of P2X7 and P2Y6 purinoceptors prevented this effect.

Conclusions

Data suggest that NTPDase3 overexpression in BM-MSCs may be a clinical surrogate of the osteogenic differentiation impairment in Pm women. Thus, besides P2X7 and P2Y6 receptors activation, targeting NTPDase3 may represent a novel therapeutic strategy to increase bone mass and reduce the osteoporotic risk of fractures in Pm women.
Serum- and xeno-free culture of human umbilical cord perivascular cells for pediatric heart valve tissue engineering
Authors: Parvin Nejad Shouka , Lecce Monica , Mirani Bahram , Machado Siqueira Nataly , Mirzaei Zahra , Santerre J. Paul , Davies John E. , Simmons Craig A.
Published: April 2023

Background

Constructs currently used to repair or replace congenitally diseased pediatric heart valves lack a viable cell population capable of functional adaptation in situ, necessitating repeated surgical intervention. Heart valve tissue engineering (HVTE) can address these limitations by producing functional living tissue in vitro that holds the potential for somatic growth and remodelling upon implantation. However, clinical translation of HVTE strategies requires an appropriate source of autologous cells that can be non-invasively harvested from mesenchymal stem cell (MSC)-rich tissues and cultured under serum- and xeno-free conditions. To this end, we evaluated human umbilical cord perivascular cells (hUCPVCs) as a promising cell source for in vitro production of engineered heart valve tissue.

Methods

The proliferative, clonogenic, multilineage differentiation, and extracellular matrix (ECM) synthesis capacities of hUCPVCs were evaluated in a commercial serum- and xeno-free culture medium (StemMACS™) on tissue culture polystyrene and benchmarked to adult bone marrow-derived MSCs (BMMSCs). Additionally, the ECM synthesis potential of hUCPVCs was evaluated when cultured on polycarbonate polyurethane anisotropic electrospun scaffolds, a representative biomaterial for in vitro HVTE.

Results

hUCPVCs had greater proliferative and clonogenic potential than BMMSCs in StemMACS™ (p < 0.05), without differentiation to osteogenic and adipogenic phenotypes associated with valve pathology. Furthermore, hUCPVCs cultured with StemMACS™ on tissue culture plastic for 14 days synthesized significantly more total collagen, elastin, and sulphated glycosaminoglycans (p < 0.05), the ECM constituents of the native valve, than BMMSCs. Finally, hUCPVCs retained their ECM synthesizing capacity after 14 and 21 days in culture on anisotropic electrospun scaffolds.

Conclusion

Overall, our findings establish an in vitro culture platform that uses hUCPVCs as a readily-available and non-invasively sourced autologous cell population and a commercial serum- and xeno-free culture medium to increase the translational potential of future pediatric HVTE strategies.

Graphical Abstract

This study evaluated the proliferative, differentiation and extracellular matrix (ECM) synthesis capacities of human umbilical cord perivascular cells (hUCPVCs) when cultured in serum- and xeno-free media (SFM) against conventionally used bone marrow-derived MSCs (BMMSCs) and serum-containing media (SCM). Our findings support the use of hUCPVCs and SFM for in vitro heart valve tissue engineering (HVTE) of autologous pediatric valve tissue. Figure created with BioRender.com.
Hermite–Hadamard and Fejér-type inequalities for strongly reciprocally (p, h)-convex functions of higher order
Authors: Li Han , Saleem Muhammad Shoaib , Ahmed Imran , Aslam Kiran Naseem
Published: April 2023

In this paper, we investigate the properties of a newly introduced class of functions, strongly reciprocally (p, h)-convex functions of higher order. We establish Hermite–Hadamard-type and Fejér-type inequalities for this class of functions. Additionally, we present fractional integral inequalities applicable to strongly reciprocally (p, h)-convex functions of higher order.
A reverse extended Hardy–Hilbert’s inequality with parameters
Authors: Luo Ricai , Yang Bicheng , Huang Xingshou
Published: April 2023

In this paper, by virtue of the symmetry principle, applying the techniques of real analysis and Euler–Maclaurin summation formula, we construct proper weight coefficients and use them to establish a reverse extended Hardy–Hilbert’s inequality with multi-parameters. Then, we obtain the equivalent forms and some equivalent statements of the best possible constant factor related to several parameters. Finally, we illustrate how the obtained results can generate some new reverse Hardy–Hilbert-type inequalities.
Non-intubated deep paralysis: a new anaesthesia strategy for vocal cord polypectomy
Authors: Fan Yichen , Chi Xiaoying , Zhu Danyan , Yin Jiemin , Liu Yaling , Su Diansan
Published: April 2023

Background

Vocal cord polyp is common otorhinolaryngological disease, traditionally treated by vocal cord polypectomy under a supporting laryngoscope with general anaesthesia. Although it is safe and controllable, it would cause some anaesthesia complications. Moreover, the complex process of general anaesthesia may significantly reduce surgical efficiency. Avoiding these problems remains an important issue.

Methods

All patients were subjected to the standard non-intubated deep paralysis (NIDP) protocol consisting of four phases. An emergency plan was launched when NIDP cannot be implemented successfully. Patient characteristics, blood gas and monitoring data were collected during NIDP. Data concerning satisfaction, complications and duration of anaesthesia and recovery were collected to assess its effectiveness.

Result

Among 20 enrolled patients, the success rate of NIDP was 95%. Only one patient failed in completing NIDP. Blood gas analysis revealed that the partial pressure of oxygen and carbon dioxide was maintained at safe levels. Monitoring during NIDP revealed fluctuations in mean arterial pressure between 110 and 70 mmHg, and the heart rate was stable at 60–100 beats per minute. The duration of anaesthesia and postoperative recovery were 13.0 ± 2.84 and 5.47 ± 1.97 min, respectively. All patients and surgeons were satisfied with NIDP, and no complications were detected before discharge.

Conclusion

NIDP can be safely applied to patients and can replace general anaesthesia in vocal cord polypectomy. It can significantly reduce the duration of anaesthesia and postoperative recovery. No anaesthesia complications occurred without intubation, and patients and surgeons were satisfied with NIDP.

Trial registrations

This single-centre, prospective study was registered on clinicaltrial.gov (NCT04247412) on 30th July 2020.
Assessment of inequality in the Common Agricultural Policy in Portugal
Authors: Viegas Miguel , Wolf Jan , Cordovil Francisco
Published: April 2023

The Common Agricultural Policy (CAP) continues to represent a substantial part of the European Union's budget. Although the second pillar is co-financed by national governments, European funds represent the vast majority of public spending on agriculture and rural development. In the case of Portugal, the CAP envelope for the current Multiannual Financial Framework (MFF 2021–2027) represents a package of €10 billion. Our article focuses on the distribution of CAP support. Based on a synthetic indicator of equity aligned with the European Union objectives of the CAP, we assess the current distribution of CAP support and estimate its distribution in the future according to the new rules that come into force in January 2023. According to the data analyzed, the major factor of inequality in the CAP in Portugal rests in the exclusion of a significant part of agricultural holdings. In this sense, it is necessary to understand the reasons for this exclusion in order to study measures so that CAP rules can contribute to a fairer distribution between farmers and between regions.