bluuebunny/crossref_metadata_2025 huggingface dataset:
Which sperm parameter limits could really guide the clinical decision in assisted reproduction?
Authors: Santi Daniele , Spaggiari Giorgia , Morini Daria , Melli Beatrice , Dalla Valentina Leonardo , Aguzzoli Lorenzo , Simoni Manuela , Villani Maria Teresa
Published: October 2022

Background

The predictive role of sperm motility and morphology was recently detected in a large sample of more than 20000 assisted reproductive technology (ART) fresh cycles. However, the complete ART procedure consisted of both fresh and frozen‐embryos transfers and only a comprehensive evaluation of the entire process could really confirm if these parameters really predict the ART success. The aim of the study was to evaluate which sperm parameter could predict the success of ART.

Methods

A retrospective, real‐world data analysis was performed, enrolling all couples attending ART from 2008 to 2021, including both fresh and frozen cycles and both in vitro fertilization (IVF) and intra‐cytoplasmic sperm injection (ICSI) procedures.

Results

Fresh cycles success (considering live birth rate) was predicted by female age (1.04 [1.02–1.06]), injected oocytes (0.96 [0.93–0.99]), embryo number (0.79 [0.75–0.83]) and progressive sperm motility (0.98 [0.97‐0.99]). On the contrary, frozen cycle outcomes were predicted only by sperm motility (0.97 [0.95–0.99]). This prediction was confirmed in IVF but not in ICSI cycles.

Conclusion

Both female and male parameters predicted the ART success considering the entire path. However, frozen cycle success was predicted only by progressive sperm motility in IVF cycles, suggesting that the potential amelioration of this male parameter is relevant to improve ART success. Those couples expected to obtain the highest embryos after fertilization (low female age and better semen parameters) will have more attempts with frozen cycles and thus would benefit from a potential treatment focused to improve sperm parameters.
Health professionals' experiences with the PEDI‐UG: What do Ugandan occupational therapists say about the utility and value of the Pediatric Evaluation of Disability Inventory (PEDI‐UG) for children with disabilities?
Authors: Ekwan Francis , Satink Ton , Kamwesiga Julius , Schulze Christina
Published: October 2022

Background

The Uganda version of Pediatric Evaluation of Disability Inventory (PEDI‐UG) was culturally adapted and validated from the PEDI‐US, a tool used to evaluate the functional capability of children with or without disability aged 6 months to 7.5 years in the areas of self‐care, mobility and social domains. A group of Ugandan occupational therapists with experience of using PEDI‐UG participated in this study to explore the question: What do Ugandan occupational therapists say about the utility and value of the PEDI‐UG for children with disabilities?

Methods

A qualitative research design was chosen to explore the participants' viewpoints concerning the utility and value of the PEDI‐UG for children with disabilities. Purposive sampling was used to recruit health professionals for the focus group discussions. Focus group discussions were carried out with 18 occupational therapists and nurses. Thematic analysis was performed to establish patterns and themes.

Results

Several challenges concerning the contextual use of PEDI‐UG were reported. For example, PEDI‐UG being culturally adapted in two languages (English and Luganda) makes it difficult for health professionals to use it for children whose caregivers are non‐English or non‐Luganda speakers. In addition, participants reported adapting the way they asked the assessment questions, struggling with how they interpreted the scores and observing the child's skills if required during PEDI‐UG interviews with caregivers.

Conclusions

The findings of this study suggest that health professionals are challenged with the use of the PEDI‐UG assessment in diverse cultural contexts and/or languages. These challenges are important considerations for the PEDI‐UG translation in different Uganda cultural languages and training health professionals on the use and value of PEDI‐UG for children with disabilities.
Multiple indurated nodular lesions on the lip, upper trunk and limbs of an 80-year-old man
Authors: Duman Nilay , Ceylan Can , Yaman Banu , Hekimgil Mine
Published: October 2022

We report multiple indurated nodular lesions on the lip, upper trunk and extremities of an 80-year-old man.
Linksüberhang in der Verteilung von melanozytären Nävi und Melanomen
Authors: Bauer‐Büntzel Christoph , Kück Fabian , Kretschmer Lutz
Published: October 2022

Hintergrund und Ziele

Eine asymmetrische Verteilung von Melanomen zugunsten der linken Körperhälfte wurde wiederholt beschrieben.

Patienten und Methodik

In einer prospektiven Querschnittstudie untersuchten wir bei 702 Patienten einer dermatologischen Klinik die Verteilung melanozytärer Nävi zwischen der linken und der rechten Körperhälfte. Außerdem bestimmten wir retrospektiv das Verhältnis von links zu rechts (L/R) von primären Melanomen, Lymphknotenmetastasen und Nävi in Sentinel‐Lymphknoten (SN) bei 2004 konsekutiven Melanomfällen.

Ergebnisse

Die L/R‐Ratios für kutane Nävi und Melanome betrugen 1,23 (95 %‐Konfidenzintervall [KI] 1,12–1,36) sowie 1,6 (95 %‐KI 1,37–1,88). Sowohl bei kutanen Nävi als auch bei Melanomen wurde der Linksüberschuss hauptsächlich in intermittierend lichtexponierter Haut gefunden. In der Nävuspopulation waren 92,4 % Rechtshänder. Die Tumordicke nach Breslow und die Ulzerationsrate waren bei linksseitigen oder rechtsseitigen primären Melanomen ähnlich.

Schlussfolgerungen

Melanozytäre Nävi und Melanome sind numerisch häufiger auf der linken Körperhälfte zu finden. Wir nehmen asymmetrische Sonneneinstrahlung als ursächlich an. Die große Mehrheit der Rechtshänder könnte ihre Körperhaltung bei Aktivitäten im Freien unbewusst so ausrichteten, dass das Licht von links einfällt. Dadurch wird der Schattenwurf durch den dominanten Arm, die Schulter oder den Kopf vermieden.
Infektionen mit Herpes‐simplex‐ und Varizella‐zoster‐Virus
Authors: Wilms Larissa , Weßollek Katharina , Peeters Theresa Barbara , Yazdi Amir Sadegh
Published: October 2022

Humane Herpesviren gehören zu den DNA‐Viren und zählen zu den häufigsten Erregern viraler Infektionen beim Menschen. Nach der Primärinfektion mit einem dieser Viren kommt es typischerweise zur Latenz mit dem Potenzial späterer Reaktivierungen, die häufiger symptomatisch sind und zum Arztbesuch führen als die Primärinfektion. In der täglichen Praxis sind Infektionen mit dem Herpes‐simplex‐Virus (HSV) und dem Varizella‐zoster‐Virus (VZV) am häufigsten vertreten. Sofern HSV‐Primärinfektionen klinisch manifest werden, gehen sie häufig mit Allgemeinsymptomen einher. HSV‐Reaktivierungen verlaufen meist harmlos und selbstlimitierend und präsentieren sich als gruppierte Bläschen auf erythematösen Grund (herpetiform). Die VZV‐Primärinfektion führt zum klinischen Bild der Varizellen (Windpocken). Bei Immunsuppression kann es zu komplizierten (nekrotisierenden, ulzerierenden, hämorrhagischen, generalisierten) Verläufen kommen. Die VZV‐Reaktivierung manifestiert sich klinisch als Herpes zoster (Gürtelrose) und kann mit starken akuten Schmerzen einhergehen.

Die Diagnosestellung erfolgt meist klinisch. Therapeutisch stehen Topika und systemische Virostatika zur Verfügung. Das adäquate therapeutische Management umfasst das Erkennen und Behandeln von Komplikationen wie der möglichen Beteiligung weiterer Organsysteme und Schmerzen. Eine Infektion in der Schwangerschaft kann zur Übertragung auf das ungeborene Kind führen.
Protective roles of tRNA‐derived small RNA tRF‐Ile‐AAT‐019 in pathological progression of psoriasis
Authors: Zeng Jinrong , Xie Yajie , Zhang Hanyi , Zhang Yuezhong , Zhang Yue , Liu Liyao , Hu Qian , Zhou Lu , Gao Lihua , Tan Wenbin , Fu Zhibing , Lu Jianyun
Published: October 2022

Psoriasis is a chronic recurrent inflammatory skin disease that is characterized by abnormal proliferation and differentiation of keratinocytes (KCs), angiogenesis and skin inflammation. Transfer RNA fragments (tRFs) are tRNA‐derived small RNAs (tsRNAs), which possess regulatory functions in many diseases. Their potential roles in the pathological development of psoriasis have not been established. We first identified differentially expressed (DE) tRFs from psoriatic skin lesions using small RNA sequencing, and collected additional clinical samples for validation. Then, we investigated the function and mechanism of target tRFs in vitro. As a result of our investigation: we identified 234 DE transcripts in psoriatic skin lesions compared with normal controls. Further functional analysis showed the downregulation of tRF‐Ile‐AAT‐019 in psoriatic lesions plays a critical role in pathogenesis since it could target 3′UTR of the serine protease serpin protein E1 (SERPINE1) gene. We next demonstrated that tRF‐Ile‐AAT‐019 could suppress SERPINE1, thus leading to decreased expressions of vascular endothelial growth factor but increased expressions of keratinocytes (KCs) differentiation markers including Keratin1 and Involucrin. In conclusion, tRF‐Ile‐AAT‐019 plays a protective role in the pathological progression of psoriasis via targeting SERPINE1, resulting in regulation of KCs differentiation and vascular proliferation biomarkers and providing a potential novel targeting pathway for the disease treatment.
Congruence couple therapy for alcohol use and gambling disorders with comorbidities (part II): Targeted areas and mechanisms of change
Authors: Lee Bonnie K. , Ofori Dei Samuel M. , Isik Erkan
Published: October 2022

Study of change mechanisms is important to advance theory development and to reveal the active components that make a critical difference in treatment. Improved outcomes in a randomized controlled trial that favored Congruence Couple Therapy (CCT) vs individual‐based Treatment‐as‐Usual (TAU) were correlated within each group. Partial correlations were used to test for mediation effects. The aggregate correlation coefficient of improved variables in addiction and mental health, couple adjustment, emotion regulation (ER) and life stress was moderate for CCT and weak for TAU. CCT showed greater number of mediating effects among improved variables than TAU. The prominence of the process mechanism of improved ER with its mediating effects for addiction and psychiatric symptoms evidenced in both groups is noteworthy, but ER improvement was significantly associated with improved couple adjustment only in CCT. Reduction in life stress in CCT was associated with a broader range of improvements in CCT compared to TAU. Correlation patterns were substantiated by CCT participants’ endorsement of treatment targets emphasizing relationship, communication, emotion, problem solving, addiction and intergenerational issues of trauma. TAU participants reported significantly lower endorsements for these treatment targets. The correlation of ER and couple adjustment suggested as a key process mechanism should be further elucidated in future studies to differentiate relationship‐based vs individual‐based models and their respective outcomes for primary clients and partners. These findings are considered preliminary, requiring larger samples and advanced modelling among variables to provide a more profound mechanism analysis.
Central bank independence in Latin America: Politicization and de‐delegation
Authors: Bodea Cristina , Garriga Ana Carolina
Published: October 2022

In the last three decades, legal delegation of monetary policy to independent central banks (CBI) has achieved the status of a global norm of good governance. The recent backlash against this independence is an important but understudied trend. Our article analyzes the potential for delegation reversals with a focus on Latin America where CBI was effective in maintaining price stability, but placed important policy constraints on governments. We theorize that, in the shadow of the global norm for CBI, the increasing distance in preferences between the government and the central bank, and the procedural hurdles to change the status quo, explain the intensity of challenges to the delegation contract or the delegated agent. An analysis of the frequency of irregular central bank leadership replacements, and instances of politicization and de‐delegation show the plausibility of our argument. We also show that, in Latin America, reforms de‐delegating monetary policy have been small, balancing the needs that justified delegation in the first place, but rolling back the most stringent constraints placed on financing the government.
‘I am not a Gentleman academic’: Telling our truths of micro‐coercive control and gaslighting in Business Schools using ‘Faction’
Authors: Edwards Michaela , Mitchell Laura , Abe Catherine , Cooper Emily , Johansson Janet , Ridgway Maranda
Published: October 2022

This paper draws from our own experiences of sexism within Business Schools to bring attention to the effects of the operation of a highly masculinized, white, cis‐gendered, and patriarchal culture, whether enacted by men or women, and to how we come to be silenced within it. Our work reflects on intersectional issues of race, health (mental and physical), and care‐work, using faction built from six paired interviews to tell a truth we feel unable to tell individually. This piece highlights the real fear of repercussions that still persist for female academics, and uses the acts of collecting data and writing differently to offer the authors a safe space in which to resist both overt and structural sexism in Business Schools. It highlights the need to take seriously those subtleties of sexism that we are often expected to put up with, those difficult‐to‐name aspects of our working lives that leave us feeling it would be “silly” to complain and act as a form of micro‐coercive control over our lives. We operationalize our collective voice as a form of activism in the academy that is situated within our individual silences.
Refugee‐owned small businesses: A typology for blended value creation
Authors: Ranabahu Nadeera , De Vries Huibert P. , Basharati Zhiyan
Published: October 2022

While it is clear that refugee‐owned small businesses generate economic value, what is less understood is small businesses' role in blended value generation for ethnic/co‐ethnic and local host communities. To explore this issue, we conducted interviews with 19 refugee business owners residing in New Zealand. Our findings concur with the extant literature that refugee‐owned businesses generate economic, social and cultural value in their adopted countries. However, these businesses can be differentiated by their value focus; that is, whether the business' sole focus is economic or a nuanced blend, where economic value is complemented by strong social and cultural outcomes. In addition, these businesses' blended value generation is concentrated in either ethnic/co‐ethnic or to local host communities. We use the findings to construct a typology of value generated by refugee‐owned businesses, based on two continuums: from economic value to blended value and from ethnic/co‐ethnic focus to local host focus.
Local application of a transcutaneous carbon dioxide paste prevents excessive scarring and promotes muscle regeneration in a bupivacaine‐induced rat model of muscle injury
Authors: Hirota Junya , Hasegawa Takumi , Inui Atsuyuki , Takeda Daisuke , Amano‐Iga Rika , Yatagai Nanae , Saito Izumi , Arimoto Satomi , Akashi Masaya
Published: October 2022

In postoperative patients with head and neck cancer, scar tissue formation may interfere with the healing process, resulting in incomplete functional recovery and a reduced quality of life. Percutaneous application of carbon dioxide (CO2) has been reported to improve hypoxia, stimulate angiogenesis, and promote fracture repair and muscle damage. However, gaseous CO2 cannot be applied to the head and neck regions. Previously, we developed a paste that holds non‐gaseous CO2 in a carrier and can be administered transdermally. Here, we investigated whether this paste could prevent excessive scarring and promote muscle regeneration using a bupivacaine‐induced rat model of muscle injury. Forty‐eight Sprague Dawley rats were randomly assigned to either a control group or a CO2 group. Both groups underwent surgery to induce muscle injury, but the control group received no treatment, whereas the CO2 group received the CO2 paste daily after surgery. Then, samples of the experimental sites were taken on days 3, 7, 14, and 21 post‐surgery to examine the following: (1) inflammatory (interleukin [IL]‐1β, IL‐6), and transforming growth factor (TGF)‐β and myogenic (MyoD and myogenin) gene expression by polymerase chain reaction, (2) muscle regeneration with haematoxylin and eosin staining, and (3) MyoD and myogenin protein expression using immunohistochemical staining. Rats in the CO2 group showed higher MyoD and myogenin expression and lower IL‐1β, IL‐6, and TGF‐β expression than the control rats. In addition, treated rats showed evidence of accelerated muscle regeneration. Our study demonstrated that the CO2 paste prevents excessive scarring and accelerates muscle regeneration. This action may be exerted through the induction of an artificial Bohr effect, which leads to the upregulation of MyoD and myogenin, and the downregulation of IL‐1β, IL‐6, and TGF‐β. The paste is inexpensive and non‐invasive. Thus, it may be the treatment of choice for patients with muscle damage.
Recovery from insulin dependence in immune checkpoint inhibitor‐associated diabetes mellitus: A case report
Authors: Okubo Marie , Hataya Yuji , Fujimoto Kanta , Iwakura Toshio , Matsuoka Naoki
Published: October 2022

Immune checkpoint inhibitor‐associated diabetes mellitus (ICI‐DM) is a rare immune‐related adverse event and is usually considered permanent. Here, we report the first case of a 54‐year‐old man with ICI‐DM who recovered from insulin dependence. He was diagnosed with lung cancer and started pembrolizumab therapy. After seven cycles, he developed ICI‐associated secondary adrenal insufficiency and started hydrocortisone supplementation. Subsequently, he complained of fatigue, and blood examinations showed hyperglycemia with ketosis. A glucagon challenge test indicated insulin dependence. He was diagnosed with ICI‐DM and insulin therapy was initiated. Pembrolizumab therapy was discontinued due to concomitant ICI‐associated hepatitis. Six months later, a glucagon challenge test result showed an improvement in insulin secretion, and insulin therapy was discontinued. The lung cancer lesions continued to shrink. Even if ICI‐DM develops, it might be possible to control the underlying cancer while avoiding lifelong insulin therapy through early discontinuation of ICI.
Improving the drying performance of parchment coffee due to the newly redesigned drying chamber
Authors: Duque‐Dussán Eduardo , Banout Jan
Published: October 2022

The Colombian coffee growers face many complications when using traditional open‐sun drying techniques such as post‐harvest process delays or incomplete grain dryness because of climate conditions. Therefore, local workshops began fabricating low‐capacity dryers simulating the industrial equipment working principles. One of the most commercialized units is a triple tray rectangular‐shaped dryer with a 31.25 kg capacity of dry parchment coffee per batch, providing the issue with an acceptable solution. However, it was redesigned into a circular shape holding a lower grain bed thickness and a vertical air inlet with a diffusive tray. Both units were simulated using the Thompson and the Michigan State University grain drying mathematical models to obtain their theoretical drying time. Then, a computational fluid dynamics simulation was conducted, attaining the unit's drying air behavior, the circular dryer exhibited notable drying times reduction and even air distribution, optimizing the dryer's performance, representing a benefit for the coffee‐growing farmers.

Practical Applications

A cylindrical arranged coffee dryer with a vertical air inlet reduces the drying time of the grain, allowing a better rentability of the grower and improves the air distribution inside the equipment, meaning that the moisture removal will occur uniformly, safeguarding that the product's final moisture content meets the required conditions for safe storage.
Optimizing Escherichia coli O157:H7 inactivation in goat's milk by thermosonication
Authors: Bernardo Yago A. A. , do Rosario Denes K. A. , Mutz Yhan S. , Castro Vinícius S. , Conte‐Junior Carlos A.
Published: October 2022

Escherichia coli O157:H7 (STEC) is one of the hazardous foodborne pathogens in milk. Although traditional preservation methods reduce contamination, they are time‐consuming or cause physicochemical changes. Therefore, we optimize STEC inactivation in goat's milk by thermosonication, an alternative to traditional treatments. Different times (1–35 min) and temperatures (45.9–74.1°C) were applied, using a Central Composite Rotatable Design (CCRD). Lipid oxidation was adopted as an optimization limiting factor. Mathematical models described STEC inactivation and lipid oxidation with high performance, considering the high R2adj (0.942 and 0.731), and low mean square error (0.065 and <0.0001) and lack‐of‐fit (0.133 and 0.183). Validation was verified by the accuracy (1.141 and 1.017) and bias (0.992 and 1.006) factors, and the relative error of prediction (0.910 and 1.000). Both variables affected STEC inactivation linearly, enhancing decontamination. Lipid oxidation was affected by time, increasing oxidation products formation. Optimization was achieved around 1–20 min/62–74°C, improving STEC inactivation (6.6 log CFU/ml) with minimal lipid oxidation (0.06 mg MDA/L). Therefore, thermosonication represents a promising technology facing to traditional methods, ensuring bacteriological safety and minimal alterations.

Practical Applications

Despite traditional methods for milk decontamination still being considered effective, there are some reports on pasteurized milk and dairy products‐related outbreaks. High‐intensity ultrasound is an emerging non‐thermal technology recently explored as a pathogen reduction method, used individually or combined. However, due to cavitation mechanism and free radicals realizing, some oxidative alterations could occur during processing. The present research paper contributes to provide a better understanding on the combined application of ultrasound and heat (thermosonication) to inactivate Escherichia coli in caprine milk. The findings herein are promising to the industrial utilization of thermosonication to obtaining safety products with minimal oxidative changes.
The role of raw materials to achieve the Sustainable Development Goals: Tracing the risks and positive contributions of cobalt along the lithium‐ion battery supply chain
Authors: da Silva Lima Lígia , Cocquyt Louise , Mancini Lucia , Cadena Erasmo , Dewulf Jo
Published: October 2022

Given the fast‐growing demand for electric mobility, the European Union (EU) has invested in responsible sourcing of battery raw materials, but the sustainability of their value chains is not fully addressed. Life cycle sustainability assessment is a tool to identify social, economic, and environmental aspects of raw materials, but it is mostly used for negative impacts, whereas the supply and use of raw materials may also lead to benefits. The Sustainable Development Goals (SDGs) can help to determine how raw materials boost or hinder the achievement of a sustainable society. In this study, the SDGs were used as a reference to assess contributions and risks of cobalt supply for electric mobility in the EU and whether this technology supports the achievement of the SDGs. The risks were determined using eight indicators focused on social risks, but environmental aspects like water quality and usage, and greenhouse gas emissions were also considered. The literature and databases were consulted to identify which SDGs receive contributions or burdens. Global and European cobalt supply scenarios were defined, considering the most representative countries. Results indicate that, although some SDGs receive positive contributions, like SDG 8 (Decent work and economic growth) and SDG 13 (Climate action), most of the identified correlations are negative, especially for SDG 3 (Good health and well‐being) and SDG 16 (Peace, justice, and strong institutions). The European scenario has a low risk toward socio‐environmental issues in 53% of the assessed aspects, whereas the global scenario presents a high risk in 47% of them.
A hierarchical Bayesian regression model that reduces uncertainty in material demand predictions
Authors: Bhuwalka Karan , Choi Eunseo , Moore Elizabeth A. , Roth Richard , Kirchain Randolph E. , Olivetti Elsa A.
Published: October 2022

Predictions of metal consumption are vital for criticality assessments and sustainability analyses. Although demand for a material varies strongly by region and end‐use sector, statistical models of demand typically predict demand using regression analyses at an aggregated global level (“fully pooled models”). “Un‐pooled” regression models that predict demand at a disaggregated country or regional level face challenges due to limited data availability and large uncertainty. In this paper, we propose a Bayesian hierarchical model that can simultaneously identify heterogeneous demand parameters (like price and income elasticities) for individual regions and sectors, as well as global parameters. We demonstrate the model's value by estimating income and price elasticity of copper demand in five sectors (Transportation, Electrical, Construction, Manufacturing, and Other) and five regions (North America, Europe, Japan, China, and Rest of World). To validate the benefits of the Bayesian approach, we compare the model to both a “fully pooled” and an “un‐pooled” model. The Bayesian model can predict global demand with similar uncertainty as a fully pooled regression model, while additionally capturing regional heterogeneity in income elasticity of demand. Compared to un‐pooled models that predict demand for individual countries and sectors separately, our model reduces the uncertainty of parameter estimates by more than 50%. The hierarchical Bayesian modeling approach we propose can be used for various commodities, improving material demand projections used to study the impact of policies on mining sector emissions and informing investment in critical material production.
Flow cytometry as an alternative method to evaluate genotoxicity of natural cosmetic actives
Authors: Ueoka Andreza R. , Sufi Bianca S. , Magalhães Wagner V. , Fernandes Liliam , Andreo‐Filho Newton , Leite‐Silva Vania R. , Lopes Patricia S.
Published: October 2022

Alternative in vitro methods are important, as there is a call to ban the use of animals in cosmetics research.

Aim

To suggest the expansion of the use of in vitro safety techniques recommended by the OECD guidelines and to propose the use of the automation of the in vitro mammalian micronucleus test method by flow cytometry to assess the genotoxic potential ofCentella asiatica, Horse Chestnut, Witch Hazel, Blend, Ecoblend, and Caffeine extracts due to their widespread use in commercial products.

Methods

Flow cytometer analysis was performed using the Accuri™ C6 equipment and analyzed using the FlowJo software. Cytotoxicity tests followed OECD 129 guidelines and Phototoxicity followed OECD/GD 432 guidelines.

Results

The results showed that the cytotoxicity assay presented a decrease in cell viability when cells were exposed toCentella asiaticafrom a concentration of 5.0%, horse chestnut 2.5%, Witch hazel 2.5%, Blend 3.13%, and Caffeine 3%, while Ecoblend at the tested concentrations did not show cytotoxicity. In the phototoxicity test, the samples at the tested concentrations showed a PIF <2 being considered potentially non‐phototoxic. Finally, in the genotoxicity automated assay, samples were considered potentially non‐genotoxic.

Conclusion

In vitro methods are of paramount importance for the development of pre‐clinical tests and the use of test automation helps to reduce the time for analysis and dissemination of results, being a determining factor for the prospect of new compounds.
Presence of pastoral fields in mountain landscapes influences prey consumption by European wildcats
Authors: Ruiz‐Villar H. , Urra F. , Jubete F. , Morales‐González A. , Adrados B. , Revilla E. , Rivilla J. C. , Román J. , Seijas J. , López‐Bao J. V. , Palomares F.
Published: October 2022

Traditional agro‐pastoral practices are more beneficial for biodiversity than intensified agricultural systems. Promotion of the growth of natural herbaceous vegetation in pastoral fields can enhance rodent populations and consequently influence ecological aspects of carnivores with rodent‐based diets, like prey consumption in the European wildcat (Felis silvestris). In this article, we investigated the effects of pastoral field extent, season and prey abundance on wildcat consumption of several prey species in the Cantabrian Mountains (NW Spain). Prey consumption in areas with presence of pastoral fields (even in low proportions) was dominated by profitable field‐dwelling rodent species such as Arvicola monticola. Consumption of Arvicola was not correlated with its abundance and was higher during summer and autumn. Apodemus dominated the wildcat diet in areas with higher forest proportion and far from pastoral fields, particularly during spring. Our results suggest that varying habitat use and seasonal changes in prey accessibility may determine wildcat prey consumption in pastoral landscapes. Our results can contribute to highlight the potential benefits of traditional and sustainable pastoral activities for the conservation of the European wildcat across its distribution range.
Human poliovirus receptor contributes to biliary atresia pathogenesis by exacerbating natural‐killer‐cell‐mediated bile duct injury
Authors: Li Yuan , Li Tian‐Yu , Qi Qiao , Zhang Min‐Ting , Tong Ming‐Xin , Su Peng‐Jun , Zhang Zhi‐Bo
Published: October 2022

Background and Aims

Natural killer (NK) cells play an important role in biliary atresia (BA) pathogenesis; human poliovirus receptor (PVR) is an important NK‐cell modulator. Here, we explored the role of PVR in BA pathogenesis.

Methods

Poliovirus receptor expression and NK cell‐associated genes were detected in human BA samples and a rotavirus‐induced BA mouse model using quantitative PCR and immunofluorescence staining. Chemically modified small interfering RNA silenced PVR expression in the BA model, and its effects on the population and function of intrahepatic NK cells were investigated using flow cytometry (FCM). The effects of PVR overexpression and knockdown on proliferation, apoptosis and NK‐cell‐mediated lysis of cultured human cholangiocytes were analysed using FCM and cell viability assays. Serum PVR, high‐mobility group box 1 (HMGB1), and interleukin‐1beta (IL‐1beta) levels were measured in a cohort of 50 patients using ELISA.

Results

Poliovirus receptor expression was upregulated in the biliary epithelium of BA patients and BA model and was positively correlated with the population and activation of intrahepatic NK cells. Silencing of PVR expression impaired the cytotoxicity of NK cells, reduced inflammation and protected mice from rotavirus‐induced BA. Activation of the TLR3‐IRF3 signalling pathway induced PVR expression in cultured cholangiocytes. PVR overexpression promoted proliferation and inhibited the apoptosis of cholangiocytes but exacerbated NK cell‐mediated cholangiocyte lysis. Serum PVR levels were elevated in BA patients and were positively correlated with HMGB1 and IL‐1beta levels.

Conclusions

Poliovirus receptor contributes to BA pathogenesis by regulating NK cell‐mediated bile duct injury; PVR has the value as a biomarker of BA.
Young magmatism and Si‐rich melts on Mars as documented in the enriched gabbroic shergottite NWA 6963
Authors: Lindner Miles , Hezel Dominik C. , Gerdes Axel , Marschall Horst R. , Brenker Frank E.
Published: October 2022

Enriched shergottites contain interstitial Si‐rich mesostasis; however, it is unclear whether such mesostasis is formed by impact or magmatic processes. We use laser ablation multicollector inductively coupled plasma mass spectrometry U–Pb measurements of minerals within the interstitial Si‐rich mesostasis and of merrillite within the coarse‐grained groundmass of Martian‐enriched gabbroic shergottite Northwest Africa (NWA) 6963. The date derived of tranquillityite, Cl‐apatite, baddeleyite, and feldspar from the Si‐rich mesostasis is 172.4 ± 6.1 Ma, and the derived merrillite date is 178.3 ± 10.6 Ma. We conclude, based on textural observation, that merrillite is a late magmatic phase in NWA 6963, that it was not produced by shock, and that its U–Pb‐system was not reset by shock. The indistinguishable dates of the gabbroic merrillite and the minerals within the Si‐rich mesostasis in NWA 6963 indicate that the Si‐rich mesostasis represents a late‐stage differentiated melt produced in the final phase of the magmatic history of the gabbroic rock and not a shock melt. This can likely be transferred to similar Si‐rich mesostases in other enriched shergottites and opens the possibility for investigations of Si‐rich mesostasis in enriched shergottites to access their magmatic evolution. Our results also provide a crystallization age of 174 ± 6 Ma (weighted average) for NWA 6963.
Mid‐Term Outcomes of Cemented Stem and Subtrochanteric Shortening Derotational Osteotomy in Total Hip Arthroplasty for Crowe IV Developmental Dysplasia
Authors: Huang Zhe‐Yu , Ling Jing , Zeng Zhi‐Min , Di Zheng‐Lin , Zhang Jun‐Hui , Tao Kun
Published: October 2022

Objective

Performing subtrochanteric osteotomy with cemented components in patients with Crowe IV developmental dysplasia of the hip (DDH) is technically challenging and not widely reported. This study aimed to evaluate the mid‐term outcomes of cemented stem total hip arthroplasty (THA) with subtrochanteric femoral shortening and transverse derotational osteotomy in patients with Crowe IV DDH.

Methods

Data collected from patients with Crowe IV DDH who underwent cemented stem THA with subtrochanteric femoral shortening and transverse derotational osteotomy between 2010 and 2018 were retrospectively evaluated. The cemented Lubinus SP II femoral component and the cementless CombiCup acetabular component were used together in all cases. These data, including Harris hip scores, limb length discrepancy (LLD), severity of limp, Trendelenburg test, bone union, length of the resected femur, limb lengthening, level of the osteotomy site, and length bridging the osteotomy site, as well as complications, were analyzed. A paired Student t‐test was used to analyze continuous variables, categorical data were compared using Fisher's exact probability test, and correlation analysis was performed using Spearman's rank correlation coefficient.

Results

Among 14 included patients (10 females and four males), the mean age was 60.4 years (range, 47–73). The mean follow‐up period was 49.1 months, and no patient was lost to follow‐up. The mean Harris hip score improved from 40.7 to 87.7. The mean LLD decreased from 52 to 12.7 mm. The mean length of the excised femoral segment was 38.4 mm, and the mean length of limb lengthening was 27.1 mm. The mean distance between the osteotomy site and the lesser trochanter was 21.1 mm after surgery. The mean length of the femoral stem bridging the osteotomy site was 97.6 mm. Finally, the mean osteotomy union time was 10.6 months. No statistically significant correlation was found between the osteotomy union time and these factors. No neurological deficits were noted. Delayed union was observed in one patient, and postoperative dislocation was observed in two patients. Cement leakage into the osteotomy gap was observed in one patient, however, no revisions were required, and no signs of loosening or migration were observed.

Conclusions

Cemented stem THA combined with subtrochanteric femoral shortening and transverse derotational osteotomy is safe and effective in treating patients with Crowe IV DDH. Rather than leading to nonunion, cement leakage may negatively affect bone healing.
Suppression of mitochondrial alternative oxidase can result in upregulation of the ROS scavenging network: some possible mechanisms underlying the compensation effect
Authors: Garmash E. V.
Published: October 2022

Mitochondrial alternative oxidase is an important protein involved in maintaining cellular metabolic and energy balance, especially under stress conditions. AOX genes knockout is aimed at revealing the functions of AOX genes. Under unfavourable conditions, AOX‐suppressed plants (mainly based on Arabidopsis AOX1a‐knockout lines) usually experience strong oxidative stress. However, a compensation effect, which consists of the absence of AOX1a leading to an increase in defence response mechanisms, concomitant with a decrease in ROS content, has also been demonstrated. This review briefly describes the possible mechanisms underlying the compensation effect upon the suppression of AOX1a. Information about mitochondrial retrograde regulation of AOX is given. The importance of ROS and mitochondrial membrane potential in triggering the signal transmission from mitochondria in the absence of AOX or disturbance of mitochondrial electron transport chain functions is indicated. The few available data on the response of the cell to the absence of AOX at the level of changes in the hormonal balance and the reactions of chloroplasts are presented. The decrease in the relative amount of reduced ascorbate at stable ROS levels as a result of compensation in AOX1a‐suppressed plants is proposed as a sign of stress development. Obtaining direct evidence on the mechanisms and signalling pathways involved in AOX modulation in the genome should facilitate a deeper understanding of the role of AOX in the integration of cellular signalling pathways.
Knock‐out of N‐glycolylneuraminic acid attenuates antibody‐mediated rejection in xenogenically perfused porcine lungs
Authors: Chaban Ryan , Habibabady Zahra , Hassanein Wessam , Connolly Margaret R. , Burdorf Lars , Redding Emily , Laird Christopher , Ranek Jolene , Braileanu Gheorghe , Sendil Selin , Cheng Xiangfei , Sun Wenji , O'Neill Natalie A. , Kuravi Kasinath , Hurh Sunghoon , Ayares David L. , Azimzadeh Agnes M. , Pierson Richard N.
Published: October 2022

Background

Antibody‐mediated rejection has long been known to be one of the major organ failure mechanisms in xenotransplantation. In addition to the porcine α1,3‐galactose (α1,3Gal) epitope, N‐Glycolylneuraminic acid (Neu5Gc), a sialic acid, has been identified as an important porcine antigen against which most humans have pre‐formed antibodies. Here we evaluate GalTKO.hCD46 lungs with an additional cytidine monophospho‐N‐acetylneuraminic acid hydroxylase (CMAH) gene knock‐out (Neu5GcKO) in a xenogeneicex vivoperfusion model

Methods

Eleven GalTKO.hCD46.Neu5GcKO pig lungs were perfused for up to 6 h with fresh heparinized human blood. Six of them were treated with histamine (H) blocker famotidine and 1‐thromboxane synthase inhibitor Benzylimidazole (BIA) and five were left untreated. GalTKO.hCD46 lungs without Neu5GcKO (n = 18: eight untreated and 10 BIA+H treated) served as a reference. Functional parameters, blood, and tissue samples were collected at pre‐defined time points throughout the perfusion

Results

All but one Neu5GcKO organs maintained adequate blood oxygenation and “survived” until elective termination at 6 h whereas two reference lungs failed before elective termination at 4 h. Human anti‐Neu5Gc antibody serum levels decreased during the perfusion of GalTKO.hCD46 lungs by flow cytometry (∼40% IgM, 60% IgG), whereas antibody levels in Neu5GcKO lung perfusions did not fall (IgMp = .007; IgGp < .001). Thromboxane elaboration, thrombin generation, and histamine levels were significantly reduced with Neu5GcKO lungs compared to reference in the untreated groups (p = .007, .005, and .037, respectively); treatment with BIA+H masked these changes. Activation of platelets, measured as CD62P expression on circulating platelets, was lower in Neu5GcKO experiments compared to reference lungs (p = .023), whereas complement activation (as C3a rise in plasma) was not altered. MCP‐1 and lactotransferin level elevations were blunted in Neu5GcKO lung perfusions (p = .007 and .032, respectively). Pulmonary vascular resistance (PVR) rise was significantly attenuated and delayed in untreated GalTKO.hCD46.Neu5GcKO lungs in comparison to the untreated GalTKO.hCD46 lungs (p = .003)

Conclusion

Additional Neu5GcKO in GalTKO.hCD46 lungs significantly reduces parameters associated with antibody‐mediated inflammation and activation of the coagulation cascade. Knock‐out of the Neu5Gc sialic acid should be beneficial to reduce innate immune antigenicity of porcine lungs in future human recipients.
Modifications of Project-Based Learning to Fit Students with Adverse Childhood Experiences
Authors: Shriner Michael , Foster Manda
Published: October 2022

The purpose of this qualitative case study was to explore the perception of modifications necessary as educators moved away from a traditional learning environment with little movement and high academic stress through the introduction of project-based learning activities specifically for this population of students. Data were collected from 1-1 interviews with five participants teaching within a mental health residential school in Missouri who hold Missouri teacher certification ranging from elementary to high school level working with 175 students, ranging in ages from 8 to 17. Additional data were collected from lesson reflections and lesson plans from classrooms of students with the same background as teacher participants over the last four school years, 2018-22, of teachers who have taught project-based learning units. Interviews, lesson reflections, and lesson plans were manually coded twice and then coded a third time using electronic coding via NVivo to ensure bias from myself was not present. This study supports using project-based learning activities with students across grade levels from elementary to high school who have encountered adverse childhood experiences. Findings from this study support perceived modifications to generate curriculum options that are non-traditional as well as relevant to students within a residential care facility school.
Impact of cancer cachexia on respiratory muscle function and the therapeutic potential of exercise
Authors: Murphy Ben T. , Mackrill John J. , O'Halloran Ken D.
Published: October 2022

Cancer cachexia is defined as a multi‐factorial syndrome characterised by an ongoing loss of skeletal muscle mass and progressive functional impairment, estimated to affect 50–80% of patients and responsible for 20% of cancer deaths. Elevations in the morbidity and mortality rates of cachectic cancer patients has been linked to respiratory failure due to atrophy and dysfunction of the ventilatory muscles. Despite this, there is a distinct scarcity of research investigating the structural and functional condition of the respiratory musculature in cancer, with the majority of studies exclusively focusing on limb muscle. Treatment strategies are largely ineffective in mitigating the cachectic state. It is now widely accepted that an efficacious intervention will likely combine elements of pharmacology, nutrition and exercise. However, of these approaches, exercise has received comparatively little attention. Therefore, it is unlikely to be implemented optimally, whether in isolation or combination. In consideration of these limitations, the current review describes the mechanistic basis of cancer cachexia and subsequently explores the available respiratory‐ and exercise‐focused literature within this context. The molecular basis of cachexia is thoroughly reviewed. The pivotal role of inflammatory mediators is described. Unravelling the mechanisms of exercise‐induced support of muscle via antioxidant and anti‐inflammatory effects in addition to promoting efficient energy metabolism via increased mitochondrial biogenesis, mitochondrial function and muscle glucose uptake provide avenues for interventional studies. Currently available pre‐clinical mouse models including novel transgenic animals provide a platform for the development of multi‐modal therapeutic strategies to protect respiratory muscles in people with cancer.

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High-Order Large Eddy Simulations of a Wind Turbine in Ducted and Open-Rotor Configurations
Authors: Ding Chi , Zhang Bin , Liang Chunlei , Visser Kenneth , Yao Guangming
Published: October 2022

High-order large eddy simulations are performed to study the performance and flow fields of a ducted wind turbine (DWT) operating at different tip speed ratios. To evaluate the effects of the duct, simulations with the same tip speed ratios are also performed on the corresponding open-rotor turbine. It is found that the ducted turbine consistently obtains higher power outputs than the open-rotor counterpart, and the duct itself enhances flow turbulence and blade trailing-edge vortices but weakens tip and hub vortices. Flow bifurcation is observed at the largest tip speed ratio and is identified to be caused by blade blockage effects. Comparative simulations are also performed on both turbines under different yaw angles. It is noticed that the ducted configuration is insensitive to small yaw angles and maintains higher power outputs than the open-rotor configuration at all yaw angles. Moreover, it is observed that the wakes of both configurations recover more quickly as the yaw angle increases.
Increasing morphological disparity and decreasing optimality for jaw speed and strength during the radiation of jawed vertebrates
Authors: Deakin William J. , Anderson Philip S. L. , den Boer Wendy , Smith Thomas J. , Hill Jennifer J. , Rücklin Martin , Donoghue Philip C. J. , Rayfield Emily J.
Published: October 2022

The Siluro-Devonian adaptive radiation of jawed vertebrates, which underpins almost all living vertebrate biodiversity, is characterized by the evolutionary innovation of the lower jaw. Multiple lines of evidence have suggested that the jaw evolved from a rostral gill arch, but when the jaw took on a feeding function remains unclear. We quantified the variety of form in the earliest jaws in the fossil record from which we generated a theoretical morphospace that we then tested for functional optimality. By drawing comparisons with the real jaw data and reconstructed jaw morphologies from phylogenetically inferred ancestors, our results show that the earliest jaw shapes were optimized for fast closure and stress resistance, inferring a predatory feeding function. Jaw shapes became less optimal for these functions during the later radiation of jawed vertebrates. Thus, the evolution of jaw morphology has continually explored previously unoccupied morphospace and accumulated disparity through time, laying the foundation for diverse feeding strategies and the success of jawed vertebrates.
Global Scripts in Transnational Legal Orders and Governance
Authors: Block-Lieb Susan
Published: October 2022

Global scripts—the rules, norms, and standards in international texts, and the tacit assumptions that surround and give meaning to them—exist on numerous issues (finance, trade, economic development, climate change, education, human rights, and gender equality), at every level of engagement (international, national, local), and at every phase of recursive norm construction and contestation. Case studies involving global scripts appear across a wide range of scholarship—considering sociological, anthropological, or sociolegal perspectives, or on international political economy, international organizations, international relations, or law and development—but because they are focused on one piece of the puzzle at a time, variation exists regarding the definition of global scripts, the distinction between legal and policy scripts, and how explicitly scripts get articulated through and with reference to law. Enhanced theorization of global scripts holds promise for connecting legal to sociolegal scholarship precisely because global scripts and scriptwriting extend beyond the realm of law and lawmaking; it would enable deeper exploration of whether, how, and why a broad range of texts and practices influence behaviors.