bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Diagnostic Yield of Exome Sequencing and Chromosomal Microarray in Short Stature
Authors: Li Qing , Chen Zefu , Wang Jie , Xu Kexin , Fan Xin , Gong Chunxiu , Wu Zhihong , Zhang Terry Jianguo , Wu Nan
Published: September 2023

Importance

Currently, the diagnostic yield of exome sequencing (ES) and chromosomal microarray analysis (CMA) for short stature cohorts is uncertain. Despite previous studies reporting the widespread use of ES and CMA, a definitive diagnostic yield has not been established.

Objective

To investigate the diagnostic yield of ES and CMA in short stature.

Data Sources

A systematic literature search was conducted using relevant keywords in 3 databases (PubMed, Embase, and Web of Science) in February 2023.

Study Selection

Eligible studies for meta-analysis were those that had at least 10 participants with short stature who were diagnosed using either ES or CMA and the number of diagnosed patients was reported. Of 5222 identified studies, 20 were eventually included in the study.

Data Extraction and Synthesis

Two independent investigators extracted relevant information from each study, which was then synthesized using proportional meta-analysis to obtain the overall diagnostic yield of ES and CMA.

Main Outcomes and Measures

The primary outcome measure was to determine the overall diagnostic yield of ES and CMA. A subgroup meta-analysis was also performed to assess if the diagnostic yield varied depending on whether ES was used as a first-tier or last-resort test. Additionally, a meta-regression was carried out to investigate how the diagnostic yield varied over time.

Results

Twenty studies were included, comprising 1350 patients with short stature who underwent ES and 1070 patients who completed CMA. The overall diagnostic yield of ES among the cohorts and CMA among the cohorts was found to be 27.1% (95% CI, 18.1%-37.2%) and 13.6% (95% CI, 9.2%-18.7%), respectively. No statistically significant difference was observed between the first-tier (27.8%; 95% CI, 15.7%-41.8%) and last-resort groups (25.6%; 95% CI, 13.6%-39.6%) (P = .83) or in the percentage of positively diagnosed patients over time. No statistically significant difference was observed between the first-tier (27.8%; 95% CI, 15.7%-41.8%) and last-resort groups (25.6%; 95% CI, 13.6%-39.6%) (P = .83) or in the percentage of positively diagnosed patients over time.

Conclusion and Relevance

This systematic review and meta-analysis provides high-level evidence supporting the diagnostic efficacy of ES and CMA in patients with short stature. The findings serve as a solid reference for clinicians when making informed decisions about recommending these genetic tests.
Multilength Scale Hierarchy in Metal‐Organic Frameworks: Synthesis, Characterization and the Impact on Applications
Authors: Tsang Min Ying , Sinelshchikova Anna , Zaremba Orysia , Schöfbeck Flora , Balsa Alejandra Durán , Reithofer Michael R. , Wuttke Stefan , Chin Jia Min
Published: September 2023

Evolutionary selection in nature has led to hierarchical structuring as a fundamental optimization strategy for biological structures, maximizing functional performance while minimizing resource usage. Precise hierarchical organization of natural materials over a wide range of length scales gives rise to unique synergistic properties that could not be achieved by single components. Despite the clear advantages offered by hierarchically structuring matter, mastering hierarchical control based on the current synthetic toolbox is still a challenge. In this review, some recent advancements in the fabrication of hierarchical metal organic framework (MOF) materials are highlighted and the advantages that arise due to different kinds of MOF hierarchy are critically analyzed. The special focus of the review lies in highlighting the applications where MOF hierarchical materials can be most impactful and describing characterization techniques currently at the disposal of scientists for the precise characterization of MOF hierarchical structures across all length scales. Finally, the intent is to inspire reticular chemists to master hierarchical control of MOF materials so as to fully utilize the advantages MOFs offer for various applications.
Design and Synthesis of Cubic K3−2xBaxSbSe4 Solid Electrolytes for K–O2 Batteries
Authors: Shao Jieren , Ao Huiling , Qin Lei , Elgin Jocelyn , Moore Curtis E. , Khalifa Yehia , Zhang Songwei , Wu Yiying
Published: September 2023

Developing K‐ion conducting solid‐state electrolytes (SSEs) plays a critical role in the safe implementation of potassium batteries. In this work, a chalcogenide‐based potassium ion SSE is reported, K3SbSe4, which adopts a trigonal structure at room temperature. Single‐crystal structural analysis reveals a trigonal‐to‐cubic phase transition at the low temperature of 50 °C, which is the lowest among similar compounds and thus provides easy access to the cubic phase. The substitution of barium for potassium in K3SbSe4 leads to the creation of potassium vacancies, expansion of lattice parameters, and a transformation from a trigonal phase to a cubic phase. As a result, the maximum conductivity of K3−2xBaxSbSe4 reaches around 0.1 mS cm−1 at 40 °C for K2.2Ba0.4SbSe4, which is over two orders of magnitude higher than that of undoped K3SbSe4. This novel SSE is successfully employed in a K–O2 battery operating at room temperature where a polymer‐laminated K2.2Ba0.4SbSe4 pellet serves as a separator between the oxygen cathode and the potassium metal anode. Effective protection of the K metal anode against corrosion caused by O2 is demonstrated.
Π‐Radical Photosensitizer for Highly Efficient and Stable Near‐Infrared Photon Upconversion
Authors: Wei Yaxiong , An Kebin , Xu Xinsheng , Ye Zeyuan , Yin Xiaojun , Cao Xiaosong , Yang Chuluo
Published: September 2023

Near‐infrared (NIR)‐to‐blue triplet–triplet annihilation upconversion (TTA‐UC) exhibits substantial potential for diverse applications, encompassing photovoltaics, photocatalysis, bioimaging, and photodynamic therapy. A major challenge in this field, however, is attaining high upconversion quantum yields (ΦUC) without using transition metals as NIR photosensitizers. This research presents an innovative organic π‐radical photosensitizer (TTM‐TPA) featuring extended absorption in the NIR region (≈760 nm) that is capable of generating pronounced anti‐Stokes emissions when coupled with suitable triplet acceptors. By eliminating energy loss associated with intersystem crossing and promoting rapid doublet–triplet energy transfer processes, the binary TTM‐TPA/perylene system achieves ΦUC values of up to 6.8% and an anti‐Stokes shift of 0.93 eV. Notably, the TTA‐UC system demonstrates exceptional stability when subjected to intense 733 nm laser irradiation (4 W cm−2), maintaining nearly constant upconversion intensity after 4 h. These findings underscore the considerable potential of doublet‐sensitized TTA‐UC for a broad array of practical applications.
Self‐Healing, Recyclable, Biodegradable, Electrically Conductive Vitrimer Coating for Soft Robotics
Authors: Spallanzani Giulia , Najafi Maedeh , Zahid Muhammad , Papadopoulou Evie L. , Ceseracciu Luca , Catalano Manuel , Athanassiou Athanassia , Cataldi Pietro , Zych Arkadiusz
Published: September 2023

Sensors and transducers enable the robots’ movements and interactions with humans and the environment. Particularly, tactile and motion sensors, even those inspired by the human skin, often miss many of its essential features. Indeed, the materials that constitute such sensors are often rigid and lack self‐healing and biodegradability. Furthermore, the large‐scale diffusion of these technologies propelled by robots spread in many aspects of the lives, from industrial to household settings, contributes heavily to the electronic and robotic waste problem. Recycling strategies for materials for robotics sensors are thus pivotal for future development. This work proposes self‐healable, recyclable, and biodegradable electrically conductive coatings. These coatings are based on conductive inks that combine graphene nanoplatelets and carbon nanofibers with a soft biodegradable vitrimer binder and are realized by spray coating. The use of the vitrimer ensures satisfying adhesion to diverse substrates, flexibility, conformability, self‐healing, and recyclability of the conductive coating. This material is a sustainable alternative to standard conductive inks for flexible electronics and soft robotics. Indeed, tests for the live monitoring of SoftHand3, the grasping system of many worldwide diffused robots, have yielded promising results. The use of biodegradable ingredients and the possibility of recycling makes it an appealing material to face the sustainability issue of today's electronics and robotics.
Recent Advances with Biomass‐Derived Carbon‐Based Catalysts for the High‐Efficiency Electrochemical Reduction of Oxygen to Hydrogen Peroxide
Authors: Wang Yuan , Zhong Haihong , Yang Weiting , Feng Yongjun , Alonso-Vante Nicolas
Published: September 2023

The oxygen reduction reaction (ORR) plays a pivotal role in electrochemical energy conversion and chemical production. Two‐electron (2e−) charge transfer for oxygen reduction is considered a promising method for the on‐site production of hydrogen peroxide (H2O2), which requires electrocatalysts with high H2O2 selectivity and ORR activity. Noble metal alloys (e.g., Pt‐Hg and Pd‐Hg) have been prevalent materials of choice due to their desirable intrinsic activity, but their scarcity and high cost seriously hinder their widespread application in practice. Self‐doped heteroatomic carbon‐based electrocatalysts, derived from abundant and inexpensive biomass, have emerged as attractive candidates for on‐site H2O2 production. This review summarizes the fundamentals and recent advances in H2O2 production via 2e− ORR, including basic catalytic mechanisms, the influence of electrolyte pH and porous structure of catalysts, selectivity assessment methods, determination of the cumulative H2O2 concentration, development of biomass‐derived carbon‐based catalyst, and electrochemical device designs. Current challenges and proposed opportunities are also presented with an emphasis on large‐scale electrochemical H2O2 synthesis.
Micromotors with Spontaneous Multipattern Motion and Microvortex for Enhanced “On‐the‐Fly” Molecule Enrichment
Authors: Lin Jinwei , Xiong Kang , Hu Junyi , Li Zhengshang , Xu Leilei , Guan Jianguo
Published: September 2023

“On‐the‐fly” molecule enrichment by micro/nanomotors obviously improves heterogeneous catalysis, trace detection, and environmental monitoring, yet faces challenges of the trade‐off between collection range and interaction time. Inspired by the versatile foraging process of predators, this work demonstrates that micromotors doing spontaneous multipattern motion with microvortex can greatly enhance “on‐the‐fly” enrichment, demonstrated by highly sensitive surface‐enhanced Raman scattering detection. It leverages an axis‐asymmetric bowl‐shaped structure and the nonlinear Ag–AgCl reaction, realizing alternating low‐velocity swinging forward and accelerated steering motions for prolonged interaction and large work area. Moreover, the bowl‐shaped microstructure bestows a micro‐vortex above the Ag side due to the competition of electric potential and pressure gradient, also extending interaction time during the acceleration. Consequently, it exhibits at least an order of magnitude larger enhancement of detection signals than the counterparts. This proof‐of‐concept study highlights the significance of motion mode and structure design in guiding flow field, offering substantial benefits for applications.
Effects of 2,3‐DPG knockout on SCD phenotype in Townes SCD model mice
Authors: Barakat Amey , Jasuja Reema , Tomlinson Lindsay , Wenzel Zane , Ramaiah Lila , Petterson Betty A. , Kapinos Brendon , Sawant Anagha , Pagan Vicente , Lintner Nathanael , Field Denise , Ahn Youngwook , Knee Kelly M.
Published: September 2023

Sickle cell disease (SCD) is a severe, multisystemic hematological disorder that impacts nearly every major organ in adults. The current approved treatments for SCD directly target mutant hemoglobin or address downstream disease pathology. Several compounds targeting reduction of 2,3‐DPG by activation of Pyruvate Kinase‐R are currently being evaluated in SCD patients. In this study, we genetically engineered a mouse lacking 2,3‐DPG on the Townes SCD mouse model background and evaluated the effects of 2,3‐DPG loss on disease pathology. Animals lacking 2,3‐DPG showed improvements in hematological markers and reductions in RBC sickling relative to native Townes mice, however, minimal difference in organ damage was observed in 2,3‐DPG deficient mice compared to native Townes animals. When animals lacking 2,3‐DPG were dosed with a compound designed to increase hemoglobin oxygen affinity, oxygen delivery related toxicity was observed.
Prospective analysis to determine barriers to allogeneic hematopoietic cell transplantation in patients with acute leukemia
Authors: Nath Karthik , Lee Jasme , Elko Theresa A. , Levy Lauren , Preston Elaina , Devlin Sean M. , Ponce Doris M. , Lin Richard J. , Shaffer Brian C. , Cho Christina , Politikos Ioannis , Jakubowski Ann A. , Park Jae H. , Rampal Raajit , Perales Miguel‐Angel , Tallman Martin S. , Barker Juliet N. , Berman Ellin , Tamari Roni , Stein Eytan , Giralt Sergio A. , Gyurkocza Boglarka
Published: September 2023

Allogeneic hematopoietic cell transplantation (allo‐HCT) is a potentially curative treatment for patients with acute leukemia. Despite this, studies have shown that only a minority of patients ultimately proceed to allo‐HCT. The primary objective of this prospective, observational study was to identify the rate of allo‐HCT in patients for whom it was recommended, and reasons why patients deemed appropriate and eligible for HCT did not subsequently undergo transplant. Between April 2016 and April 2021, adult patients with newly diagnosed or relapsed/refractory acute leukemia were enrolled at the time of induction/reinduction therapy. Initial transplantation workup and allo‐HCT recommendations were made during the early phase of induction/reinduction. Of the 307 enrolled patients, allo‐HCT was recommended to 85% (n = 259), of whom 66% (n = 170) underwent transplant. Donor sources comprised 54% human leukocyte antigen (HLA)‐matched unrelated donors, 20% HLA‐matched sibling donors and HLA‐mismatched graft sources with 15% umbilical cord blood units, 8% HLA‐mismatched unrelated donors, and 4% HLA‐haploidentical donors. The most common reason for transplant disqualification in the 89 patients in whom it was initially recommended was persistent/relapsed disease (70%), followed by early patient death (10%). In this prospective study, we report a high allo‐HCT rate, which may be due to early transplant referral and workup. The main allo‐HCT barrier was disease control, followed by early patient death. With the increasing availability of HLA‐mismatched graft sources, the lack of donor availability was not a transplant barrier. Further development of novel transplant strategies for patients not achieving remission and improvements in induction regimens could result in increased allo‐HCT utilization.
Pd‐catalyzed Three‐component Cross‐coupling of Arylhydrazides with Arylboronic Acids and TFBen: Facile Access to Diaryl Ketones via Denitrogenative Carbonylation
Authors: Zhang Wei , Ai Chunxin , Wang Kaikai , Guo Jiao , Zhao Baoli
Published: September 2023

Carbonylation with CO surrogates is one of the most common methods for introduction of carbonyl groups in ketone synthesis. However, arylhydrazides have not been used as an aryl source in this denitrogenative method even though they are cheap and accessible. Here, we report development of palladium catalysis for the three‐component reactions of arylboronic acids, CO‐surrogates (benzene‐1,3,5‐triyl triformate), and arylhydrazides under oxygen conditions to produce diaryl ketones. (Hetero)arylhydrazides, as well as (hetero)arylboronic acids are suitable reaction partners, and good functional group compatibility was achieved. This method could be used for streamlined synthesis of diaryl ketones, ketoprofen and fenofibrate.
TestDimorph: An R package for analysis of interpopulation sexual dimorphism differences using summary statistics
Authors: Abulnoor Bassam A. , Attia MennattAllah Hassan , Konigsberg Iain R. , Konigsberg Lyle W.
Published: September 2023

Objective

The degree of sexual dimorphism in certain traits between males and females differ from one sample to another. Although trait differences by sex are often reported in bioanthropological research, few studies test for statistical significance or make raw data available. TestDimorph is the first R package dedicated to testing and comparing the degree of sexual dimorphism among different samples by leveraging summary statistics.

Materials and Methods

We provide two approaches of analysis of inter‐sample differences in degree of sexual dimorphism: univariate and multivariate for two or more samples. The methods follow upon publications primarily from the AJBA. Within‐sex size variability between samples is compared using one‐way ANOVA followed by control for multiple pairwise comparisons. In addition, we compute the overlapping area between the density functions of two normal distributions from the mixture intersection index or the non‐overlapping area using the dissimilarity index as well as Hedges' g with inferential support using the 95% confidence interval. Finally, we use a multivariate analysis of differences in patterning of sexual dimorphism between samples.

Results

We demonstrate various results from applying TestDimorph functions to data supplied with the package.

Discussion

The package has many features including functionality for working with summary statistics, simulating data from summary statistics, and the extraction of summary statistics from raw data, so that the entire analysis can be performed through the package.
Biomaterial‐Based Gene Delivery to Central Nervous System Cells for the Treatment of Spinal Cord Injury
Authors: McGuire Tara K. , Stasiewicz Martyna , Woods Ian , Dervan Adrian G. , O’Brien Fergal J.
Published: September 2023

Spinal cord injury (SCI) is a devastating traumatic injury often causing permanent loss of function. The challenge of treating SCI stems from the development of a complex pathophysiology at the site of injury, involving multiple biochemical cascades, widespread inflammation, blood supply interruption, inhibitory scar formation, and poor regrowth of injured axons. Clinical options are limited to surgical stabilization and attempt to ameliorate secondary damage following injury. Gene therapy has significant potential to tackle multiple aspects of SCI and improve functional outcomes. The emergence of a diverse array of biomaterial‐based nonviral nanoparticle vectors capable of delivering gene‐modifying nucleic acids offers the potential to improve the efficiency and specificity of genetic cargos for spinal cord regeneration. In this review, the progress that has been made in the field of SCI repair and the different types of nanoparticles and nucleic acid cargoes that have been used are outlined, placing a particular focus on the different cell types and pathways targeted. While many challenges remain, a perspective on the future of the field of nanoparticle‐mediated gene delivery for SCI is provided, including using biomaterial scaffolds engineered specifically for SCI to deliver gene therapeutics and the exciting opportunities that exist in the post‐COVID landscape.
Ein Zweidimensionales Konjugiertes Poly(benzimidazobenzophenanthrolin) Leiter‐Covalent Organic Framework für schnelle Protonenspeicherung**
Authors: Wang Mingchao , Wang Gang , Naisa Chandrasekhar , Fu Yubin , Gali Sai Manoj , Paasch Silvia , Wang Mao , Wittkaemper Haiko , Papp Christian , Brunner Eike , Zhou Shengqiang , Beljonne David , Steinrück Hans‐Peter , Dong Renhao , Feng Xinliang
Published: September 2023

Die elektrochemische Protonenspeicherung spielt eine wesentliche Rolle bei der Entwicklung von hochleistungsfähigen Energiespeichern der nächsten Generation, z. B. von wasserbasierten Batterien. Zweidimensionale konjugierte kovalente organische Gerüstverbindungen (2D c‐COFs) sind vielversprechende Elektrodenmaterialien, aber ihre Protonen‐ und Metallionen‐Insertionsmechanismen sind nach wie vor schwer zu beschreiben, die Protonenspeicherung in COFs ist kaum erforscht. Hier stellen wir ein auf Perinon‐basiertes Poly(benzimidazobenzophenanthrolin) (BBL)‐Leiter‐2D c‐COF zur schnellen Protonenspeicherung sowohl in einem milden wässrigen Zn‐Ionen‐Elektrolyt als auch in einer starken Säure vor. Wir zeigen, dass die entladenen C−O− Gruppen aufgrund der beträchtlichen π‐Delokalisierung in Perinon eine weitgehend reduzierte Basizität aufweisen, was dem 2D c‐COF eine besondere Affinität zu Protonen verleiht sowie in schneller Kinetik resultiert. Dadurch weist unsere 2D c‐COF‐Elektrode eine herausragende Ratenfähigkeit bis 200 A g−1 (über 2500 C) auf und übertrifft damit bisherige konjugierten Polymere, COFs und metallorganischen Gerüstverbindungen. Unsere Arbeit ist das erste Beispiel für reine Protonenspeicherung in COFs und unterstreicht das große Potenzial von konjugierten 2D‐BBL‐Leiterer‐Polymeren für zukünftige energetische Anwendungen.
Plasmon‐Induced Radical‐Radical Heterocoupling Boosts Photodriven Oxidative Esterification of Benzyl Alcohol over Nitrogen‐Doped Carbon‐Encapsulated Cobalt Nanoparticles
Authors: Hao Quanguo , Li Zhenhua , Shi Yiqiu , Li Ruizhe , Li Yuan , Wang Liang , Yuan Hong , Ouyang Shuxin , Zhang Tierui
Published: September 2023

Selective oxidation of alcohols under mild conditions remains a long‐standing challenge in the bulk and fine chemical industry, which usually requires environmentally unfriendly oxidants and bases that are difficult to separate. Here, a plasmonic catalyst of nitrogen‐doped carbon‐encapsulated metallic Co nanoparticles (Co@NC) with an excellent catalytic activity towards selective oxidation of alcohols is demonstrated. With light as only energy input, the plasmonic Co@NC catalyst effectively operates via combining action of the localized surface‐plasmon resonance (LSPR) and the photothermal effects to achieve a factor of 7.8 times improvement compared with the activity of thermocatalysis. A high turnover frequency (TOF) of 15.6 h−1 is obtained under base‐free conditions, which surpasses all the reported catalytic performances of thermocatalytic analogues in the literature. Detailed characterization reveals that the d states of metallic Co gain the absorbed light energy, so the excitation of interband d‐to‐s transitions generates energetic electrons. LSPR‐mediated charge injection to the Co@NC surface activates molecular oxygen and alcohol molecules adsorbed on its surface to generate the corresponding radical species (e.g., ⋅O2−, CH3O⋅ and R‐⋅CH‐OH). The formation of multi‐type radical species creates a direct and forward pathway of oxidative esterification of benzyl alcohol to speed up the production of esters.
Modified lignin‐induced composite hydrogels with good mechanical properties, adhesion, and UV resistance for strain sensors
Authors: Chen Jing , Li Bengang , Ma Xiaofeng , Zhou Shuai , Gu Qun , Bian Hua , Luo Zhenyang
Published: September 2023

The flexibility and functionality of conductive hydrogels are crucial to applications under various scenarios and complex environments. Due to single functionality and weakness in mechanical properties, the application of conductive hydrogels in flexible wearable devices remains a challenge. In this study, lignin‐graft‐poly(acrylic acid) (LPAA) was incorporated into acrylamide (AM)/sodium chloride (NaCl) solution to fabricate composite conductive hydrogels. NaCl enhanced the conductivity of hydrogels. The hydrogen‐bond crosslinking network was formed by adding LPAA into the hydrogel, which enhanced the mechanical properties of the hydrogel (the tensile strength was 96 kPa and the compressive strength was 0.54 MPa). With LPAA added, the adhesion of hydrogels was improved to 11.3 kPa on glass, 14.2 kPa on plastic, and 17.3 kPa on metal. LPAA also provided excellent UV shielding ability (99.95%) for hydrogels while maintaining good transparency. The conductive hydrogels with good sensitivity (Gauge Factor = 2.51, 100%–500%) and stability can be used as strain sensors for monitoring physical activity. It is expected to be a candidate material for future flexible wearable electronic devices.
Synthesis and characterization of long‐chain (C20 ~ C48) fatty acid amides (FAAms) from soybean oil and alkyl amines for phase change material applications
Authors: Zheng Yue , Martinez Carlos J. , Youngblood Jeffrey P.
Published: September 2023

Bio‐based organic phase change materials (PCMs) have drawn attention considering their great value in environmental sustainability as a latent heat storage strategy. In this study, bio‐based fatty acid amides (FAAms) were synthesized directly from soybean oil and different amines through a solvent‐free reaction with a non‐toxic catalyst (DABCO). The chemical and thermal properties were confirmed by FT‐IR, NMR, DSC, and TGA measurements. The effects of oil saturation and chain length were investigated. FAAms were successfully synthesized from most of the primary alkyl amines with high purity and yield. Fifteen different FAAms exhibit high latent heat (up to 202 J/g) with a single‐phase transition peak. A general trend of increasing enthalpy of fusion, narrower phase transition temperature range, higher melting temperature, and better thermal stability was found with increasing FAAms chain length. An opposite trend was observed for some long‐chain FAAms (C > 42). Overall, a wide choice of green, organic PCMs with comparable thermal properties to petroleum based PCMs is provided in this work. Those FAAms with high working temperatures (>100°C) could expand the application of organic PCM to different fields such as steam generation, textile, rubber industry, etc.
Secretory production of 7‐dehydrocholesterol by engineered Saccharomyces cerevisiae
Authors: Ke Xia , Pan Zi‐Hao , Du Hong‐Fei , Shen Yi , Shen Ji‐Dong , Liu Zhi‐Qiang , Zheng Yu‐Guo
Published: September 2023

Background

7‐Dehydrocholesterol (7‐DHC) can be directly converted to vitamin D3 by UV irradiation and de novo synthesis of 7‐DHC in engineered Saccharomyces cerevisiae has been recognized as an attractive substitution to traditional chemical synthesis. Introduction of sterol extracellular transport pathway for the secretory production of 7‐DHC is a promising approach to achieve higher titer and simplify the downstream purification processing.

Methods and results

A series of genes involved in ergosterol pathway were combined reinforced and reengineered in S. cerevisiae. A biphasic fermentation system was introduced and 7‐DHC was found to be enriched in oil‐phase with an increased titer by 1.5‐folds. Quantitative PCR revealed that say1, atf2, pdr5, pry1‐3 involved in sterol storage and transport were all significantly induced in sterol overproduced strain. To enhance the secretion capacity, lipid transporters of pathogen‐related yeast proteins (Pry), Niemann–Pick disease type C2 (NPC2), ATP‐binding cassette (ABC)‐family, and their homologues were screened. Both individual and synergetic overexpression of Plant pathogenesis Related protein‐1 (Pr‐1) and Sterol transport1 (St1) largely increased the de novo biosynthesis and secretory productivity of 7‐DHC, and the final titer reached 28.2 mg g−1 with a secretion ratio of 41.4%, which was 26.5‐folds higher than the original strain. In addition, the cooperation between Pr‐1 and St1 in sterol transport was further confirmed by confocal microscopy, molecular docking, and directed site‐mutation.

Conclusion

Selective secretion of different sterol intermediates was characterized in sterol over‐produced strain and the extracellular export of 7‐DHC developed in present study significantly improved the cell biosynthetic capacity, which offered a novel modification idea for 7‐DHC de novo biosynthesis by S. cerevisiae cell factory.
Macroscopic modeling of the growth and substrate consumption of wild type and genetically modified Pichia pastoris
Authors: Joseph Jewel Ann , Akkermans Simen , Van Impe Jan F.
Published: September 2023

Pichia pastoris is a popular yeast platform to generate several industrially relevant products which have applications in a wide range of sectors. The complexities in the processes due to the addition of a foreign gene are not widely explored. Since these complexities can be dependent on the strain characteristics, promoter, and type of protein produced, it is vital to investigate the growth and substrate consumption patterns of the host to facilitate customized process optimization. In this study, the growth rates of P. pastoris GS115 wild type (WT) and genetically modified (GM) strains grown on glycerol and methanol in batch cultivation mode were estimated and the model providing the best representation of the true growth kinetics based on substrate consumption was identified. It was observed that the growth of P. pastoris exhibits Haldane kinetics on glycerol rather than the most commonly used Monod kinetics due to the inability of the latter to describe growth inhibition at high concentrations of glycerol. Whereas, the cardinal parameter model, a newly proposed model for this application, was found to be the best fitting to describe the growth of P. pastoris on methanol due to its ability to describe methanol toxicity. Interestingly, the findings from this study concluded that in both substrates, the genetically engineered strain exhibited a higher growth rate compared to the WT strain. Such an observation has not been established yet in other published works, indicating an opportunity to further optimize the carbon source feeding strategies when the host is grown in fed‐batch mode.
Two‐way reaction of versatile peroxidase with artificial lignin enhances low‐molecular weight fractions
Authors: Spasojević Dragica , Prodanović Olivera , Mutavdžić Dragosav , Sekuljica Nataša , Jovanović Jelena , Maksimović Vuk , Radotić Ksenija
Published: September 2023

In recent years, versatile peroxidase (VP) has emerged as a promising enzyme for biotechnological applications, as it can oxidize lignin without the external mediators. To gain insights into the breakdown process of artificial lignin by VP, reaction between the two was studied. Degradation products were fractionated using ultrafiltration and analyzed by RP‐ high performance liquid chromatography with mass detection (HPLC‐MS) chromatography. Four fractions were obtained based on their molecular sizes: >10, 3–10, 1–3, and <1 kDa. Interestingly, while VP did not significantly alter the yields of these fractions, the chromatograms revealed the presence of oligomers with different molecular weights (MWs) resulting from the enzymatic activity. The VP exhibits a dual role in its enzymatic activity: both degrading and synthesizing these oligomers. This was confirmed by principal component analysis (PCA). The positive correlations were found between certain oligomers (D1 and D2, D5 and D6, as well as between D7, D10, T2, and T4), suggesting their simultaneous degradation. On the other hand, a negative correlation was found between the monomer and some oligomers (D7, D10, T2, and T4), indicating the decomposition of these oligomers into monomers. These findings shed light on the intricate interplay between VP and artificial lignin, offering valuable insights for potential applications in lignin valorization.
Recent advances in upstream process development for production of recombinant adeno‐associated virus
Authors: Ou Jianfa , Tang Yawen , Xu Jianlin , Tucci Julian , Borys Michael C. , Khetan Anurag
Published: September 2023

Recombinant adeno‐associated virus (rAAV) is rapidly emerging as the preferred delivery vehicle for gene therapies, with promising advantages in safety and efficacy. Key challenges in systemic in‐vivo rAAV gene therapy applications are the gap in production capabilities versus potential market demand and complex production process. This review summarizes current available information on rAAV upstream manufacturing processes and proposed optimizations for production. The advancements in rAAV production media were reviewed with proposals to speed up the cell culture process development. Furthermore, major methods for genetic element delivery to host cells were summarized with their advantages, limitations, and future directions for optimization. In addition, culture vessel selection criteria were listed based on production cell system, scale, and development stage. Process control at the production step was also outlined with an in‐depth understanding of production kinetics and quality control.
Student therapists' experiences of learning using a machine client: A proof‐of‐concept exploration of an emotionally responsive interactive client (ERIC)
Authors: Prescott Julie , Ogilvie Lisa , Hanley Terry
Published: September 2023

Background

The use of artificial intelligence (AI) is increasing in many areas of healthcare, including mental healthcare. The automated nature of such technologies has the potential to be developed to work with large numbers of people. This paper examines the way that student therapists experience using an interactive text‐based machine client as a training tool.

Methodology

Chatbot technology has been used to develop an emotionally responsive interactive client (ERIC). This introduces individuals to concepts of person‐centred therapy (empathy, congruence and unconditional positive regard) by using a series of pre‐programmed scenarios. Twenty‐eight student therapists evaluated ERIC's potential as a learning tool. Individuals were recruited from one university from a postgraduate and an undergraduate counselling programme.

Findings

Feedback was generally positive, with all reporting that they enjoyed engaging with ERIC as a learning method. ERIC helped individuals consider their understanding of counselling skills in a non‐judgemental environment. Participants felt the scenarios were realistic and engaging, with many reporting that they felt they were engaging with a real client/person due to ERIC's ability to express emotions.

Discussion

ERIC is at the proof‐of‐concept phase. From the feedback presented here, it is evident that it can be a useful learning tool. Further development of ERIC with feedback from a larger sample is, however, required. ERIC is currently a text‐based client, and further development would like to see the intervention be voice‐activated to enhance the experience. ERIC can be further enhanced and adapted to be a useful learning platform for student therapists, as well as for students in other (healthcare‐related) disciplines, whereby a client or patient is required.
From the iron cage to ‘La Jaula de Oro’: Music as a cultural object
Authors: Rodriguez Liliana V.
Published: September 2023

ThenorteñobandLos Tigres del Norte(LTDN) are widely known as the ‘voice’ of the undocumented community for using their music as a vehicle to create and raise social consciousness on pressing issues of immigration. Utilizing Griswold's cultural diamond approach to analysing culture, I examine the culture/society relationship that emerges from their musical repertoire. Using this sociological model of culture, I argue that the wide receptiveness of their music is based on the constructed phenomenon that more than just a celebration of dance rhythms and entertainment their music poses itself as a cultural object attached with ideologies. By appropriating the dominant national discourse that has traditionally belittled, discriminated and dehumanized immigrants in the United States, in particular immigrants of Latin American descent, the music of LTDN markets itself less as a product and more as a cultural component of identity empowering marginalized communities by not only telling their stories but also nurturing a sense of pride. Analysing 56 songs within the musical repertoire of LTDN from 1970 to 2022, I demonstrate how their music on immigrant‐related struggles serves to reinforce a Latina/o collective identity by fostering solidarity, educating the public and instilling pride.
ASER: Adapted squared error relevance for rare cases prediction in imbalanced regression
Authors: Kou Ying , Fu Guang‐Hui
Published: September 2023

Many real‐world data mining applications involve using imbalanced datasets to obtain predictive models. Imbalanced data can hinder the model performance of learning algorithms in rare cases. Although there are many well‐researched classification task solutions, most of them cannot be directly applied to regression task. One of the challenges in imbalanced regression is to find a suitable evaluation and optimization standard that can improve the predictive ability of the model without severe model bias. Based on the importance of rare cases, this study proposes a new evaluation metric called adapted squared error relevance (ASER) by defining new relevance function and weighting functions. This metric weights data points by defining the importance of rare cases and assigns different weights to losses of the same size at different rare cases, thus enabling the model selected by this evaluation metric to better predict rare cases. ASER is compared with SER on 32 real datasets and 9 simulated datasets to verify the predictive performance of the selected model at rare cases. The experimental results show that the new evaluation metric ASER can obtain a high prediction performance at rare cases, while also not losing too much prediction accuracy in common cases.
Breast cancer survivorship experiences among Black women
Authors: Ko Naomi Y. , Fikre Tsion G. , Buck Anne K. , Restrepo Emily , Warner Erica T.
Published: September 2023

Background

Black women experience significant disparities in breast cancer across the care continuum, including survivorship. Ensuring that Black women obtain high‐quality follow‐up care is critical but understudied. This study was aimed at understanding the experiences and needs of Black women during breast cancer survivorship.

Methods

Black patients diagnosed with invasive breast cancer within the past 5 years were invited to participate in a focus group and complete a survey. Focus groups examined the following: (1) the transition from active treatment to survivorship; (2) interactions with health care providers; (3) survivorship experiences, information needs, and preferences; and (4) existing educational materials. Results were thematically coded and analyzed for main themes. Surveys collected information on sociodemographics, health care experiences, quality of life, lifestyle, and education needs.

Results

The study enrolled 53 participants, 43 of whom completed a survey and participated in one of 11 focus groups. The median age was 54 years, 44% had private insurance, 81% were English speaking, and 86% had completed their treatment more than a year before. Participants identified the importance of relationships with health care providers, gaps in survivorship care, experiences with cancer‐related symptoms, challenges with mental health, worry about recurrence, body image, cancer financial toxicity, and coping through religion and spirituality. Unmet needs were centered around preparation for long‐term symptoms, diet and physical activity, emotional support, and more explanations of information resources. Participants reported preferences for educational videos, personal stories, and culturally relevant content.

Conclusions

Some Black breast cancer survivors may have specific challenges and preferences. Supportive interventions that address these concerns can be responsive and help to ameliorate disparities.
Mammography screening beliefs and barriers through the lens of Black women during the COVID‐19 pandemic
Authors: Bea Vivian J. , An Anjile , Gordon Ashley M. , Antoine Francesse S. , Wiggins Plyshette Y. , Hyman Diane , Robles‐Rodriguez Evelyn
Published: September 2023

Background

Mammography is an effective screening tool that leads to decreased breast cancer mortality, yet minority women continue to experience barriers. The coronavirus disease 2019 (COVID‐19) pandemic has been proven to have negatively affected minority communities, yet its effect on mammography screening habits in Black women is uncertain. The purpose of this study was to evaluate breast cancer mammography screening habits and barriers for Black women in two northeast communities amid the COVID‐19 pandemic.

Methods

The study participants were Black women aged 40 years or older who were recruited from community outreach initiatives. Study coordinators conducted telephone surveys to determine mammography screening behaviors, perceptions, and psychosocial factors.

Results

Two hundred seventy‐seven surveys were completed. Two hundred fifty‐six patients who reported ever having a mammogram became the study population of interest. One hundred seventy‐four of these patients (68%) reported having a mammogram within the past year (nondelayed), and 82 (32%) had a mammogram more than a year ago (delayed). Only thirty‐one of the delayed participants (37.8%) had private insurance. There was a significant difference in the mean score for mammography screening perceived barriers for nondelayed participants (mean = 9.9, standard deviation [SD] = 3.6) versus delayed participants (mean = 11.2, SD = 4.3, p = .03). There was also a significant difference in the mean score when they were asked, “How likely is it that ‘other health problems would keep you from having a mammogram’?” (p = .002).

Conclusions

Barriers to mammography screening for Black women during the COVID‐19 era include insurance, competing health issues, and perceptions of screening. Community outreach efforts should concentrate on building trust and collaborating with organizations to improve screening despite the COVID‐19 pandemic.
NiO/ZnO Composite Derived Metal‐Organic Framework as Advanced Electrode Materials for Zinc Hybrid Redox Flow Battery
Authors: Lakshmanan Priya , Janshirani Premnahth Jeyaraj , Rengapillai Subadevi , Sivakumar Marimuthu
Published: September 2023

NiO/ZnO composite derived metal‐organic framework (MOF) is used as to modify carbon felt (CF) via a conventional solid‐state reaction followed by ultrasonication. The prepared electrode material is used in zinc‐hybrid redox flow batteries (RFBs) due to their high redox activity of Zn2+/Zn. The electrochemical performance of composite modified CF and pre‐treated CF was studied by cyclic voltammetry (CV) in 0.5 M aqueous zinc chloride with 5 M potassium hydroxide solutions showed clear confirmation for enhanced electrocatalytic activity. The unique porous structure of NiO/ZnO‐derived MOF with increased surface area improves the battery behavior significantlyThe peak current ratio for the as‐prepared material is about 3 times higher than that of the pre‐treated CF due to more active sites. Zinc‐based RFB with modified CF electrode exhibited better electrochemical performance with voltage efficiency (VE, 88 %), which is higher than true redox flow batteries.
A wide input range, 94% peak efficiency auto‐select multi‐mode boost converter for thermoelectric energy harvesting
Authors: Hajiakbari Fatemeh , Ashraf Mohammadreza
Published: September 2023

In this paper, a high‐efficiency DC–DC boost converter is proposed for thermal energy harvesting systems. The converter's efficiency is improved using a low‐power digital operating mode detector circuit. The operating mode detector circuit changes the converter's operating mode between the continuous conduction mode (CCM) and discontinuous conduction mode (DCM) at a specific input voltage (boundary input voltage), which reduces the total losses, thus improves the efficiency and increases the input voltage range. Besides, the proper boundary input voltage is calculated as a function of the boost converter's parameters. Finally, the proposed converter is designed in a standard 0.18 μm CMOS process. Simulation results show that the peak efficiency of the converter can be up to 94%, 60.4%, and 35% at 300, 20, and 15 mV of the open‐circuit voltage, respectively.
Hypothyroidism and subclinical hypothyroidism are associated with fatty pancreas (Non‐Alcoholic Fatty Pancreas Disease)
Authors: Bayyigit Akif , Gokden Yasemin , Onol Suzan , Ozek Fatma Z. , Saglam Selin , Adas Mine
Published: September 2023

Objectives

Increasing visceral fat deposition with raised prevalence of obesity and metabolic syndrome is associated with many adverse conditions, especially cardiovascular diseases and diabetes. Although there are many studies that investigate hepatic steatosis in hypothyroidism and subclinical hypothyroidism, to the best of our knowledge, there is no study investigating its relationship with pancreatic steatosis. In the present study, the purpose was to investigate this relationship.

Methods

Physical and biochemical characteristics of 30 hypothyroid, 30 subclinical hypothyroid, and 30 euthyroid volunteers were recorded in this cross‐sectional study. Liver and pancreatic steatosis were evaluated with ultrasonography.

Results

It was found that pancreatic steatosis was increased in hypothyroid and subclinical groups when compared to the control group, and hepatic steatosis was increased in the subclinical group when compared to the control group (steatosis; p = 0.002, p = 0.004, p = 0.001, p = 0.002, p = 0.002, p = 0.004). Pancreatic steatosis was positively correlated with age, hepatic steatosis, height, weight, BMI, waist circumference, hip circumference, hemoglobin, Insulin, alanine aminotransferase, Triglyceride, Creatinine, and gamma‐glutamyltransferase and was negatively correlated with total cholesterol, high‐density lipoproteins.

Conclusions

The prevalence of pancreatic steatosis was found to be increased in hypothyroidism and subclinical hypothyroidism when compared with the euthyroid control group.
Detection of capromorelin in urine following oral and dermal routes of administration
Authors: Sobolevsky Tim , Walpurgis Katja , Goergens Christian , Fedoruk Matthew , Lewis Laura , Ahrens Brian , Thevis Mario
Published: September 2023

Capromorelin is a growth hormone secretagogue. Despite promising results to alleviate muscle‐wasting in the elderly, it has not advanced further in human development. Subsequent studies demonstrated capromorelin's ability to increase food intake in animals, leading to approval in the United States and Europe as an appetite stimulant for cats (Elura) and dogs (Entyce). Capromorelin is prohibited in sports due to its ability to stimulate growth hormone production and enhance performance. However, given that its veterinary preparation is formulated as a highly concentrated solution (20 or 30 mg/mL) delivered orally, incidental ingestion or dermal absorption may result in an adverse analytical finding (AAF) by way of direct exposure during oral administration to a pet. An administration study was conducted by either oral or transdermal application of capromorelin solution to mimic the scenario of inadvertent exposure to the drug. Ingestion of 30 μg of capromorelin orally (equivalent to 1 μL of Entyce) resulted in detectable amounts of capromorelin in urine for up to 48 h after administration with a maximum urinary concentration of 7 ng/mL. Importantly, when applied directly to the skin on the hands in larger quantities mimicking a pet administration exposure scenario (30 mg or 1 mL of Entyce), capromorelin was also detected reaching a maximum urinary concentration of 0.7 ng/mL. Athletes and testing authorities should be aware of the risk of an AAF arising due to incidental exposure to veterinary preparations of capromorelin. To our knowledge, before 2022, no positive test for capromorelin had ever been reported.