bluuebunny/crossref_metadata_2025 huggingface dataset:
EFEMP1 haploinsufficiency causes a Marfan‐like hereditary connective tissue disorder
Authors: Forghani Irman , Lang Steven H. , Rodier Matthew J. , Bivona Stephanie A. ,   Undiagnosed Diseases Network, Morales Alejo A. , Zuchner Stephan , Bademci Guney , Tekin Mustafa
Published: February 2024

Phenotypic features of a hereditary connective tissue disorder, including craniofacial characteristics, hyperextensible skin, joint laxity, kyphoscoliosis, arachnodactyly, inguinal hernia, and diverticulosis associated with biallelic pathogenic variants in EFEMP1 have been previously described in four patients. Genome sequencing on a proband and her mother with comparable phenotypic features revealed that both patients were heterozygous for a stop‐gain variant c.1084C>T (p.Arg362*). Complementary RNA‐seq on fibroblasts revealed significantly reduced levels of mutant EFEMP1 transcript. Considering the absence of other molecular explanations, we extrapolated that EFEMP1 could be the cause of the patient's phenotypes. Furthermore, nonsense‐mediated decay was demonstrated for the mutant allele as the principal mechanism for decreased levels of EFEMP1 mRNA. We provide strong clinical and genetic evidence for the haploinsufficiency of EFEMP1 due to nonsense‐medicated decay to cause severe kyphoscoliosis, generalized hypermobility of joints, high and narrow arched palate, and potentially severe diverticulosis. To the best of our knowledge, this is the first report of an autosomal dominant EFEMP1‐associated hereditary connective tissue disorder and therefore expands the phenotypic spectrum of EFEMP1 related disorders.
Robust, Ultrafast and Reversible Photoswitching in Bulk Polymers Enabled by Octupolar Molecule Design
Authors: Fang Long , Lin Ziwei , Zhang Yang , Ye Bin , Li Jing , Ran Qishan , Wang Xiaotong , Yang Meijia , Yuan Zhongke , Lin Xiaofeng , Yu Dingshan , Chen Xudong , Li Quan
Published: February 2024

Improving the photoswitching rate and robustness of photochromic molecules in bulk solids is paramount for practical applications but remains an on‐going challenge. Here, we introduce an octupolar design paradigm to develop a new family of visible light organic photoswitches, namely multi‐branched octupolar Stenhouse Adducts (MOPSAs) featuring a C3‐symmetrical A3‐(D‐core) architecture with a dipolar donor–acceptor (D–A) photochrome in each branch. Our design couples multi‐dimensional geometric and electronic effects of MOPSAs to enable robust ultrafast reversible photoswitching in bulk polymers. Specifically, the optimal MOPSA (4 wt %) in commercial polyurethane films accomplishes nearly 100 % discoloration in 6 s under visible light with ∼ 100 % thermal‐recovery in 17.4 s at 60 °C, while the acquired kinetics constants are 3∼7 times that of dipolar DASA counterpart and 1∼2 orders of magnitude higher than those of reported DASAs in polymers. Importantly, the MOPSA‐doped polymer films sustain 500 discoloration/recovery cycles with slow degradation, superior to the existing DASAs in polymers (≤30 cycles). We discover that multi‐dipolar coupling in MOPSA enables enhanced polarization and electron delocalization, promoting the rate‐determining thermal cyclization, while the branched and non‐planar geometry of MOPSA induces large free volume to facilitate the isomerization. This design can be extended to develop spiropyran or azobenzene‐based ultrafast photochromic films. The superior photoswitching performance of MOPSAs together with their high‐yield and scalable synthesis and facile film processing inspires us to explore their versatile uses as smart inks or labels for time‐temperature indicators, optical logic encryption and multi‐levelled data encryption.
Standardization of ALEX index for the ecological quality assessment under European Framework Directives in Mediterranean sensitive habitats affected by biological invasions
Authors: Piazzi Luigi , Castriota Luca , Livi Silvia , de Biasi Anna Maria , Pacciardi Lorenzo , Pertusati Marco , Pretti Carlo , Gennaro Paola
Published: February 2024

This paper aims at providing a standardized procedure to assess the ecological quality of Mediterranean marine habitats in relation to biological invasions by macroalgae through the employment of the ALEX index.

Available data from previous ALEX applications were used to optimize the sampling design and to propose a standardized procedure. The procedure was applied to the main Mediterranean sensitive habitats, coralligenous reefs and meadows of the endemic seagrass Posidonia oceanica, at two sites in the north‐western Mediterranean Sea.

A total of 73 native macroalgal taxa and four introduced taxa (the Chlorophyta Caulerpa cylindracea and the turf forming Rhodophyta Acrothamnion preissii, Womersleyella setacea and Asparagopsis spp.) were identified. Coralligenous reefs exhibited a higher abundance of both C. cylindracea and introduced turf species, while P. oceanica meadows were mostly affected by W. setacea and A. preissii.

The application of ALEX for different years on coralligenous reefs highlighted the consistency of the index over time in the absence of further invasions.

The use of ALEX index with other ecological quality indices showed similar patterns in both habitats. The concurrent assessment of the ecological quality of ecosystems by generic indices and the level of invasion through ALEX index may be a useful approach for answer to requirements of the European Directives and to plan even more complete and effective conservation programmes.
Catalytic pyrolysis of lignocellulosic and algal biomass using NaOH as a catalyst
Authors: Ram Shri , Ku Xiaoke , Vasudev Vikul
Published: February 2024

In this work, the pyrolysis of barley straw (BS) and brown algae (BA) mixed with NaOH as a catalyst was compared. Four different catalyst‐to‐biomass mass ratios (i.e., 6:100, 8:100, 10:100, and 12:100) and five pyrolysis heating rates were examined. The kinetic parameters (e.g., the activation energy and pre‐exponential factor) were evaluated using the Friedman method and kinetic models. For noncatalytic pyrolysis, the average activation energies for BS and BA samples were 139.71 and 183.19 kJ mol−1, respectively. However, the addition of catalyst generally increased the average activation energy of BS samples but decreased that of BA samples. The enthalpy change and Gibbs free energy change revealed that both catalytic and noncatalytic pyrolysis processes were nonspontaneous and endothermic, and the inclusion of catalyst increased the average entropy change of the BS samples but decreased that of the BA samples. Char and biochar yields after pyrolysis were also analyzed quantitatively. These observations provide insight into the differences in catalytic pyrolysis between lignocellulosic and algal biomass species.
Methods of biotechnology Biotech BioBrawl: A competition‐based learning approach to biotechnology
Authors: Skiados Nicholas , Rehman Rabeea Summer , Riley Megan , Schroeder Kersten T.
Published: February 2024

Biotechnology students entering the workforce often struggle in their application of textbook knowledge to build the solutions that we see in science and health fields today. Some students may be naive to what a job in the biotechnology industry can encompass. Students should graduate having a firm grasp of the prospects of their field and have the confidence to begin contributing to the growth of the industry. For this, it is necessary for students to be able to start practising applications in their coursework before they graduate. A competition titled “Biotech BioBrawl” was incorporated in the University of Central Florida's Methods in Biotechnology (MCB4721C/MCB5722C) course agenda during the semester of Fall 2021. This competition challenged students to harness innovation and applied science in a group setting that led to the development and pitch of an original idea to a panel of judges with various biotechnology industry experiences.
Gas Evolution as a Tool to Study Reaction Kinetics Under Biomimetic Conditions
Authors: Meeus Eva J. , Laan Petrus C. M. , Ham Rens , de Bruin Bas , Reek Joost N. H.
Published: February 2024

The field of bioorthogonal chemistry is rapidly growing, presenting successful applications of organic and transition metal‐catalysed reactions in cells and living systems (in vivo). The development of such reactions typically proceeds through many iterative steps focused on biocompatibility and fast reaction kinetics to ensure product formation. However, obtaining kinetic data, even under simulated biological (biomimetic) conditions, remains a challenge due to substantial concentrations of salts and biomolecules hampering the use of typically employed solution‐phase analytical techniques. In this study, we explored the suitability of gas evolution as a probe to study kinetics under biomimetic conditions. As proof of concept, we show that the progress of two transition metal‐catalysed bioorthogonal chemical reactions can be accurately monitored, regardless of the complexity of the medium. As such, we introduce a protocol to gain more insight into the performance of a catalytic system under biomimetic conditions to further progress iterative catalyst development for in vivo applications.
Asymmetric Synthesis of Dihydrospirotryprostatin B via a Silica Gel‐Mediated Cyclization of Tryptamine‐Ynamide
Authors: Han Changhong , Yang Lu , Yao Kaizong , Zhang Sen , Fu Jiayue , Sun Hanyang , Xu Hongsheng , Lin Bin , Cheng Maosheng , Liu Yongxiang
Published: February 2024

Comprehensive Summary

An asymmetric synthesis of dihydrospirotryprostatin B was achieved in 15 steps (8 purifications) from L‐tryptophan. The main feature of our synthetic strategy is the efficient construction of spirocyclic oxindole intermediate containing a chiral quaternary carbon center, involving the silica gel‐mediated cyclization of tryptamine‐ynamide and oxidation under neat conditions.
Evaluation of the Effects of Meal Type and Acid‐Reducing Agents on the Pharmacokinetics of Cilofexor, a Selective Nonsteroidal Farnesoid X Receptor Agonist
Authors: Weber Elijah J. , Younis Islam R. , Wang Lulu , Xiao Deqing , Barchuk William T. , Othman Ahmed A.
Published: February 2024

Cilofexor is a nonsteroidal farnesoid X receptor agonist being developed in combination with firsocostat/semaglutide for the treatment of nonalcoholic steatohepatitis. This phase 1 study evaluated the effects of food and acid‐reducing agents (ARAs) on the pharmacokinetics of cilofexor (100‐ or 30‐mg fixed‐dose combination with firsocostat) in healthy participants. Cohorts 1 (n = 20, 100 mg) and 2 (n = 30, 30 mg) followed a 3‐period, 2‐sequence crossover design and evaluated effects of light‐fat and high‐fat meals. Cohort 3 (n = 30, 100 mg fasting) followed a 2‐period, 2‐sequence crossover design and evaluated the effects of a 40‐mg single dose of famotidine. Cohort 4 (n = 18, 100 mg) followed a 3‐period, 2‐sequence crossover design and evaluated the effects of a 40‐mg once‐daily regimen of omeprazole administered under fasting conditions or following a light‐fat meal. Administration with light‐fat or high‐fat meals resulted in no change and an ∼35% reduction in cilofexor AUC, respectively, relative to the fasting conditions. Under fasting conditions, famotidine increased cilofexor AUC by 3.2‐fold and Cmax by 6.1‐fold, while omeprazole increased cilofexor AUC by 3.1‐fold and Cmax by 4.8‐fold. With a low‐fat meal, omeprazole increased cilofexor exposure to a lesser extent (Cmax 2.5‐fold, AUC 2.1‐fold) than fasting conditions. This study suggests that caution should be exercised when cilofexor is administered with ARAs under fed conditions; coadministration of cilofexor (100 or 30 mg) with ARAs under fasting conditions is not recommended with the current clinical trial formulations.
Gender‐differentiated preference for sweetpotato traits and their drivers among smallholder farmers: Implications for breeding
Authors: Namirimu Josephine , Okello Julius Juma , Kizito Andrew Muganga , Ssekiboobo Agnes M.
Published: February 2024

To improve sweetpotato (Ipomoea batatas L.) productivity, several improved high‐yielding varieties have been developed by breeders. However, many farmers still grow low‐yielding landraces. Farmers choose varieties to grow based on their preference for the attributes of those varieties. Varietal preferences have been shown to differ between males and females. This study assessed farmer preferences for sweetpotato traits and the factors that drive the choice of most preferred traits. It used a uniquely large data set collected through personal interviews with male and female sweetpotato growers. The study employed multinomial probit regression to examine the drivers of trait preference. It finds a higher preference for production‐oriented traits among farmers in general and especially older ones. This is, however, lower among more educated farmers who mainly prefer risk‐averting traits, and those growing local varieties who mainly prefer quality traits. Hence, alongside production‐oriented traits, other traits critical for the acceptance of new varieties by farmers in their respective contexts should not be ignored.
Alzheimer's disease biomarker utilization at first referral enhances differential diagnostic precision with simultaneous exclusion of Creutzfeldt‐Jakob disease
Authors: Wang Zitianyu , Lewis Victoria , Stehmann Christiane , Varghese Shiji , Senesi Matteo , McGlade Amelia , Ellett Laura J. , Doecke James D. , Eratne Dhamidhu , Velakoulis Dennis , Masters Colin L. , Collins Steven J. , Li Qiao‐Xin
Published: February 2024

Most suspected Creutzfeldt‐Jakob disease (CJD) cases are eventually diagnosed with other disorders. We assessed the utility of investigating Alzheimer's disease (AD) biomarkers and neurofilament light (NfL) in patients when CJD is suspected. The study cohort consisted of cerebrospinal fluid (CSF) samples referred for CJD biomarker screening wherein amyloid beta 1‐42 (Aβ1‐42), phosphorylated tau 181 (p‐tau181), and total tau (t‐tau) could be assessed via Elecsys immunoassays (n = 419) and NfL via enzyme‐linked immunosorbent assay (ELISA;n = 161). In the non‐CJD sub cohort (n = 371), 59% (219/371) had A+T– (abnormal Aβ1‐42 only) and 21% (79/371) returned A+T+ (abnormal Aβ1‐42 and p‐tau181). In the 48 CJD subjects, a similar AD biomarker profile distribution was observed. To partially address the prevalence of likely pre‐symptomatic AD, NfL was utilized to assess for neuronal damage. NfL was abnormal in 76% (25/33) of A+T– subjects 40 to 69 years of age, 80% (20/25) of whom had normal t‐tau. This study reinforces AD as an important differential diagnosis of suspected CJD, highlighting that incorporating AD biomarkers and NfL at initial testing is worthwhile.
Individual behaviour, growth, survival and vulnerability to hunting in a large mammal
Authors: Cusson Pier‐Oliver , Pelletier Fanie
Published: February 2024

Humans have exploited wild animals for thousands of years. Recent studies indicate that harvest‐induced selection on life‐history and morphological traits may lead to ecological and evolutionary changes. Less attention has been given to harvest‐induced selection on behavioural traits, especially in terrestrial systems. We assessed in a wild population of large terrestrial mammals whether decades of hunting led to harvest‐induced selection on trappability, a proxy of risk‐taking behaviour. We investigated links between trappability, horn growth and survival across individuals in early life and quantified the correlations between early‐life trappability and horn growth with availability to hunters and probability of being shot. We found positive among‐individual correlations between early‐life trappability and horn growth, early‐life trappability and survival and early‐life horn growth and survival. Faster growing individuals were more likely to be available to hunters and shot at a young age. We found no correlations between early‐life trappability and availability to hunters or probability of being shot. Our results show that correlations between behaviour and growth can occur in wild terrestrial population but may be context dependent. This result highlights the difficulty in formulating general predictions about harvest‐induced selection on behaviour, which can be affected by species ecology, harvesting regulations and harvesting methods used. Future studies should investigate mechanisms linking physiological, behavioural and morphological traits and how this effects harvest vulnerability to evaluate the potential for harvest to drive selection on behaviour in wild animal populations.
The transformative potential of experimentation as an environmental governance approach: The case of the Dutch peatlands
Authors: Van Den Ende Mandy A. , Hegger Dries L. T. , Mees Heleen L. P. , Driessen Peter P. J.
Published: February 2024

Governance of societal transformations toward sustainability is needed to address the fundamental system failures responsible for environmental problems. Possible transformation pathways range from radical shifts to more incremental change. Experimentation is seen as a form of incremental change, but its actual transformative potential is debated. The transformative potential of experimentation is especially questionable for environmental problems characterizing a “creeping crisis” because this problem type is not particularly a lever for social change. Our empirical research contributes to this debate by systemically evaluating the significance (degree of change) and sufficiency (reach of change) of experiments relating to an environmental problem characterizing a creeping crisis that appears to be predominantly governed through experimentation: land subsidence in Dutch peatlands. We found that experiments have indeed proved to be significant for local regime actors because most have tested technical innovations that kept the overall land use system intact. However, experimentation was less significant in terms of reflecting the complexity of environmental problems; that would require a more diverse set of technical, social, legal, and planning experiments from which the strategy most suitable for specific landscape contexts could be determined. We also found signs of accumulation of outcomes, but whether this eventually initiates transformative change or creates a technological lock‐in can only be determined with longitudinal research. To enhance the transformative potential of experimentation, particularly as a governance approach for creeping crises, attention must be paid to actor and institutional features since they shape experiments. Hence, we conclude with design principles for transformative experimentation.
Tricuspid annular disjunction with varying degrees of tricuspid regurgitation in the setting of Takotsubo syndrome
Authors: Gaylard Benjamin , Montaño‐Krawczuk Angela , Haugaa Kristina , Bäck Magnus
Published: February 2024

Tricuspid annular disjunction (TAD) is concomitant in approximately half of mitral annular disjunction (MAD) cases. Here we report a case of echocardiographically isolated TAD detected during Takotsubo syndrome (TTS) complicated by a transient aggravation of tricuspid regurgitation. An 87‐year‐old female was admitted at the emergency department with ST segment elevation. Coronary angiography findings were consistent with TTS. Transthoracic echocardiography (TTE) showed a left ventricular apical aneurysm with incidental finding of TAD with ‘torrential’ tricuspid regurgitation. Importantly, no concomitant MAD was detected on TTE. No significant arrhythmias were detected on telemetry surveillance. Follow up TTE showed improvement in left ventricular function with reduced regional wall abnormalities. TAD was still present although the tricuspid regurgitation had reduced to ‘moderate’. The patient was discharged home after 23 days of hospital stay. The present case illustrates the need of further investigations into TAD and its clinical implications for acute TR in TTS.
Co‐Evaporated CuSbSe2 Thin Films for Solar Cells
Authors: Wan Lei , Xu Guanglei , Jiao Yufei , Zhang Zishuo , Mao Xiaoli , Niu Haihong , Wang Huan , Xu Jinzhang , Wang Xingzhu , Zhou Ru , Xu Baomin
Published: February 2024

CuSbSe2 is a promising light‐harvesting material for solar cells, which shows advantages including low melting point, low cost, and environmental friendliness, as well as excellent optoelectronic properties. In this work, a three‐source co‐evaporation method is employed to deposit CuSbSe2 thin films for the first time. Well‐crystallized and pure‐phase CuSbSe2 films are obtained through a two‐stage co‐evaporation, and the reaction mechanism of CuSbSe2 is revealed based on the phase evolution during film deposition process. It is also found that the growth atmosphere during the high‐temperature stage of co‐evaporation deposition exerts a significant impact on the phase, composition, crystallinity, and optoelectronic properties of CuSbSe2 films. Eventually, a Mo/CuSbSe2/CdS/ZnO:Al (AZO)/Ag‐structured solar cell is successfully constructed, yielding a considerable power conversion efficiency of 1.83%.
Adverse childhood experiences, low self‐esteem, and salient stimulus response in eating disorders
Authors: Lagan Sarah , Shott Megan E. , Frank Guido K. W.
Published: February 2024

Background

Adverse childhood experiences (ACEs) are elevated in individuals with eating disorders (EDs), but how the neurobiology of EDs and ACEs interact is unclear.

Methods

Women 18–45 years old with anorexia nervosa (AN, n = 38), bulimia nervosa (BN, n = 32), or healthy controls (n = 60) were assessed for ACEs and ED behaviours and performed a taste‐conditioning task during brain imaging. Mediation analyses tested relationships between ACE score, self‐esteem, and ED behaviours.

Results

ACE scores were elevated in EDs and correlated positively with body mass index (p = 0.001), drive for thinness (p = 0.001), and body dissatisfaction (p = 0.032); low self‐esteem mediated the relationship between ACEs and body dissatisfaction, drive for thinness, and bulimia severity. ACE scores correlated negatively (FDR‐corrected) with unexpected, salient stimulus receipt in AN (substantia nigra) and BN (anterior cingulate, frontal and insular cortex, ventral striatum, and substantia nigra). When ACE scores were included in the model, unexpected stimulus receipt brain response was elevated in EDs in the anterior cingulate and ventral striatum.

Conclusions

ACEs attenuate unexpected salient stimulus receipt response, which may be a biological marker for altered valence or hedonic tone perception in EDs. Low self‐esteem mediates the relationships between ACEs and ED behaviours. Adverse childhood experiences should be assessed in biological studies, and their effects targeted in treatment.
Energetic/exergetic study of Kalina and refrigeration bottoming cycles on different solar‐driven organic Rankine cycles
Authors: Dehghan Masood , Akbari Ghasem , Montazerin Nader , Maroufi Arman
Published: February 2024

Combination of different power cycle scenarios is of prime importance in achieving maximum energy utilization from solar‐driven multigeneration systems. To fulfill such objective, the present article proposes a novel energy distribution system, leveraging a combination of direct‐fed organic Rankine cycle (ORC) and a bottom‐cycled arrangement of Kalina cycle system (KCS) and double‐effect absorption refrigeration cycle (DEARC) within a parabolic trough solar collector powered trigeneration system. The study explores three different ORC configurations: simple ORC; ORC equipped with internal heat exchanger (ORC‐IHE) and regenerative ORC (RORC). It is shown that although higher efficiencies are achievable from a larger portion of PTSC energy absorbed by the ORC, the ORC energy absorption is limited by ORC evaporator temperature differences, and there is unused energy that can be recovered by the KCS, based on the proposed energy system. The results indicate that the addition of bottoming KCS leads to a considerable increase in the exergy efficiency of ORC, ORC‐IHE and RORC‐based systems by 11.7%, 30.7% and 32.6%, respectively. The impact of different ORC configurations, key ORC parameters and various organic working fluids on the energetic/exergetic efficiencies is also examined to find the optimal configuration. In terms of overall energetic/exergetic efficiencies, the highest performance belongs to ORC (78.4%/30.4%) while the lowest energetic and exergetic efficiencies belong to ORC‐IHE and RORC, respectively (56.3% and 25.65%). On the basis of a comparative study with the available literature, these values are higher than what is already reported for similar solar‐driven multigeneration systems. Appropriate thermal match and lower exergy destruction in the KCS, and bottoming cycle arrangement of the DEARC are the main reasons for such enhanced performance. This research not only contributes valuable insights into efficient solar‐driven systems but also sets a new benchmark for performance metrics in the existing literature.
The regulatory landscape of genetically engineered crops in Pakistan
Authors: Awais Muhammad , Rao Abdul Qayyum , Sadaqat Sahar , Yaqoob Amina , Bhutta Muhammad Saad , Shakoor Sana , Yasmeen Aneela , Ajmal Sara , Ghramh Hamed A. , Khan Khalid Ali , Bakhsh Allah
Published: February 2024

Genome editing technology has become part and parcel of biotechnological approach to understand the genetic basis of different biological processes in an organism and for its application in different fields. The basic need of world food production demands a highly variable population of plants with maximum diversity of agronomic traits of interest. Genome editing is unique in the sense that it provides a direct approach to generate targeted variability. The worldwide availability of genome‐edited crop varieties in the global market is approaching, whereas the decision to deal with genome‐edited (GE) crops differently from genetically transformed crop varieties is under discussion all around the world. GE may add allochthonous or autochthonous sequences into the genome much like traditional transgenesis or cisgenesis. Considering this fact, the United States declared genome‐edited crops as conventional. Many countries such as Japan, UK, China, and Brazil have already legislated their GE products and their products are near to get entry to the market. In Pakistan, academic and research‐based scientific institutions have been working on genome‐edited crops by using CRISPR (clustered regularly interspaced short palindromic repeats) Cas technology. As being a signatory of the Cartagena protocol, every case of GM (Genetically modified) or GE (Genetically Engineered) should be passed through the Technical Advisory Committee which will be decided on case‐to‐case bases depending upon its nature of random or targeted mutation. Pakistan Environmental Protection Act, Intellectual Property Organization of Pakistan Act, Seed amendment act, and PBR (The Plant Breeders' Rights Act) are the major constitutional acts employed and working for the regulations of GM alongside GE crops. Now, discussions of scientists, academicians and officials from regulatory body are in process for the design of GE crop commercialization policy in Pakistan. The CRISPR‐Cas9 system is now the most in‐demand piece of technology and has become an indispensable component of research and development in the field of life sciences.
Effect of fortifying sorghum and wheat with Longhorn grasshopper (Ruspolia differens) powder on nutritional composition and consumer acceptability of biscuits
Authors: Ronoh Amos Kipkemoi , Serrem Charlotte Atsango , Tumwebaze Susan Balaba , Were Gertrude Mercy
Published: February 2024

This study aimed at improving the nutrient composition and protein quality of biscuits made from sorghum and wheat through fortification with Longhorn Ruspolia differens powder (RDP) for use as a supplementary food targeting children vulnerable to protein–energy malnutrition (PEM). Ten biscuit formulations were prepared by replacing a part of wheat and sorghum–wheat flours with 5, 15, 20, and 40% RDP. To establish the nutrient content of biscuits, proximate and mineral compositions were determined. The amino acid composition, reactive lysine and in vitro protein digestibility were determined for protein quality. Compositing wheat or wheat–sorghum biscuits with RDP increased the protein, fat, ash, and crude fiber by percentages as high as 118, 37, 133, and 573%, respectively. Mineral content increased with, iron, zinc, and potassium as high as 161, 219, and 169%, respectively. The lysine, reactive lysine and in vitro protein digestibility of the fortified biscuits increased significantly, relative to the 100% cereal biscuits. Fortification with RDP significantly improved the amino acid content of the biscuits but had a marginal effect on improvement of the lysine score and did not meet the reference pattern for children aged 3–10 years. The Protein Digestibility Corrected Amino Acid Score (PDCAAS) of wheat–sorghum and wheat biscuits improved by 6% to 47% and 2% to 33%, respectively, compared to the control biscuits. The fortified biscuits were liked by the consumers. The RDP‐fortified biscuits have the potential to alleviate PME in developing countries.
Building capacity for equitable healthcare workforce policy, learning from migrant healthcare workers: A qualitative study with Romanian physicians working in Germany during COVID‐19
Authors: Kuhlmann Ellen , Ungureanu Marius‐Ionuț , Thilo Nancy , Fehr Leonie Mac , Cosma Nicoleta‐Carmen , Brînzac Monica Georgina , Dopfer‐Jablonka Alexandra
Published: February 2024

Background

Attention to the healthcare workforce has increased, yet comprehensive information on migrant healthcare workers is missing. This study focuses on migrant healthcare workers' experiences and mobility patterns in the middle of a global health crisis, aiming to explore the capacity for circular migration and support effective and equitable healthcare workforce policy.

Methods

Romanian physicians working in Germany during the COVID‐19 pandemic served as an empirical case study. We applied a qualitative explorative approach; interviews (n = 21) were collected from mid of September to early November 2022 and content analysis was performed.

Results and Discussion

Migrant physicians showed strong resilience during the COVID‐19 crisis and rarely complained. Commitment to high professional standards and career development were major pull factors towards Germany, while perceptions of limited career choices, nepotism and corruption in Romania caused strong push mechanisms. We identified two major mobility patterns that may support circular migration policies: well‐integrated physicians with a wish to give something back to their home country, and mobile cosmopolitan physicians who flexibly balance career opportunities and personal/family interests. Health policy must establish systematic monitoring of the migrant healthcare workforce including actor‐centred approaches, support integration in destination countries as well as health system development in sending countries, and invest in evidence‐based circular migration policy.
Healthcare workforce equity for health equity: An overview of its importance for the level of primary health care
Authors: Santric Milicevic M. , Scotter C. D. P. , Bruno‐Tome A. , Scheerens C. , Ellington K.
Published: February 2024

Background

Healthcare workforce crises often stem from healthcare workers' inequities. This study provides an overview of the main PHC workforce policy questions related to health equity, offering examples of evidence necessary to support the implementation of policies and strategies that increase equity in the health workforce and access to the PHC workforce and services.

Methods

The equity‐related policies in PHC and workforce were linked with the indicators listed in the Global Health Workforce Network Data and Evidence Hub and guidelines for health workforce management.

Results

The policy‐relevant questions in PHC cover many workforce issues such as the optimal size, equitable distribution, relevant competencies to ensure equitable healthcare access, and equitable approaches for retention, training, recruitment, benefits and incentive schemes and governance. This will require intersectionality evidence of the optimised staffing to PHC workload, that PHC practitioners' training demonstrates evidence‐based knowledge aligned with locally relevant expertise.

Conclusion

Critical for equitable PHC access and health equity is the establishment of efficient measurement of PHC workforce equity and its implications for population health. Using indicators that measure health and workforce equity in research, policy, and practices may improve recruitment and retention, and respond more effectively to the PHC workforce crises.
A color‐based tumor segmentation method for clinical ex vivo breast tissue assessment utilizing a multi‐contrast brightfield imaging strategy
Authors: Wang Roujia , Ekem Lillian , Gallagher Jennifer , Factor Rachel E. , Hall Allison , Ramanujam Nimmi
Published: February 2024

We demonstrate an automated two‐step tumor segmentation method leveraging color information from brightfield images of fresh core needle biopsies of breast tissue. Three different color spaces (HSV, CIELAB, YCbCr) were explored for the segmentation task. By leveraging white‐light and green‐light images, we identified two different types of color transformations that could separate adipose from benign and tumor or cancerous tissue. We leveraged these two distinct color transformation methods in a two‐step process where adipose tissue segmentation was followed by benign tissue segmentation thereby isolating the malignant region of the biopsy. Our tumor segmentation algorithm and imaging probe could highlight suspicious regions on unprocessed biopsy tissue to guide selection of areas most similar to malignant tissues for tissue pathology whether it be formalin fixed or frozen sections, expedite tissue selection for molecular testing, detect positive tumor margins, or serve an alternative to tissue pathology, in countries where these services are lacking.
Study of dispersion extraction for optical coherence tomography imaging
Authors: Gui Jiahui , Zhang Xiao , Li Qin
Published: February 2024

Dispersion mismatch of optical coherence tomography (OCT), caused by inherent dispersion of biological sample, leads to axial resolution degradation and image blurring. However, the dispersion of biological samples may carry characteristic information of itself. Therefore, it is useful and important to extract dispersion as an additional parameter of biological samples. Here, we study and compare five categories of conventional OCT dispersion extraction methods first. The results show that the iterative method has the best accuracy and stability. Furthermore, we propose an improved iterative method, which achieves higher accuracy and stability in simulation compared with conventional methods. Then, the dispersion values of optical glasses are extracted experimentally utilizing the proposed method. The extracted values are consistent well with reference values. Furthermore, we apply the proposed method for extracting the dispersion characteristics of zebrafish eye. With the proposed method, OCT‐based analysis of dispersion characteristics could be a powerful tool in clinical practice.
Intrinsic factors behind long COVID: IV. Hypothetical roles of the SARS‐CoV‐2 nucleocapsid protein and its liquid–liquid phase separation
Authors: Eltayeb Ahmed , Al‐Sarraj Faisal , Alharbi Mona , Albiheyri Raed , Mattar Ehab H. , Abu Zeid Isam M. , Bouback Thamer A. , Bamagoos Atif , Uversky Vladimir N. , Rubio‐Casillas Alberto , Redwan Elrashdy M.
Published: February 2024

When the SARS‐CoV‐2 virus infects humans, it leads to a condition called COVID‐19 that has a wide spectrum of clinical manifestations, from no symptoms to acute respiratory distress syndrome. The virus initiates damage by attaching to the ACE‐2 protein on the surface of endothelial cells that line the blood vessels and using these cells as hosts for replication. Reactive oxygen species levels are increased during viral replication, which leads to oxidative stress. About three‐fifths (~60%) of the people who get infected with the virus eradicate it from their body after 28 days and recover their normal activity. However, a large fraction (~40%) of the people who are infected with the virus suffer from various symptoms (anosmia and/or ageusia, fatigue, cough, myalgia, cognitive impairment, insomnia, dyspnea, and tachycardia) beyond 12 weeks and are diagnosed with a syndrome called long COVID. Long‐term clinical studies in a group of people who contracted SARS‐CoV‐2 have been contrasted with a noninfected matched group of people. A subset of infected people can be distinguished by a set of cytokine markers to have persistent, low‐grade inflammation and often self‐report two or more bothersome symptoms. No medication can alleviate their symptoms efficiently. Coronavirus nucleocapsid proteins have been investigated extensively as potential drug targets due to their key roles in virus replication, among which is their ability to bind their respective genomic RNAs for incorporation into emerging virions. This review highlights basic studies of the nucleocapsid protein and its ability to undergo liquid–liquid phase separation. We hypothesize that this ability of the nucleocapsid protein for phase separation may contribute to long COVID. This hypothesis unlocks new investigation angles and could potentially open novel avenues for a better understanding of long COVID and treating this condition.
BRG1 mediates epigenetic regulation of TNFα‐induced CCL2 expression in oral tongue squamous cell carcinoma cells
Authors: Xu Mingyan , Lu Xuemei , Zhu Feixiang , Sun Xue , Yao Hongfa , Zhang Junling , Chen Weishi , Zhu Haohao , Liu Fan , Shi Song Lin , Deng Xiaoling
Published: February 2024

Strong evidence has indicated that upregulation of chemokine (CC motif) ligand‐2 (CCL2) expression and the presence of an inflammatory tumor microenvironment significantly contribute to the migratory and invasive properties of oral squamous cell carcinoma, specifically oral tongue squamous cell carcinoma (OTSCC). However, the precise epigenetic mechanism responsible for enhanced CCL2 expression in response to the inflammatory mediator tumor necrosis factor alpha (TNF‐α) in OTSCC remains inadequately elucidated. We have demonstrated that the production of CCL2 can be induced by TNF‐α, and this induction is mediated by the chromatin remodel protein BRG1. Through the use of a chromatin immunoprecipitation (ChIP) assay, we have found that BRG1 was involved in the recruitment of acetylated histones H3 and H4 at the CCL2 promoter, thereby activating TNF‐α‐induced CCL2 transcription. Furthermore, we have observed that recruitment of NF‐κB p65 to the CCL2 promoter was increased following BRG1 overexpression and decreased after BRG1 knockdown in OTSCC cells. Our Re‐ChIP assay has shown that BRG1 knockdown completely inhibits the recruitment of both acetylated histone H3 or H4 and NF‐κB to the CCL2 promoter. In summary, the findings of our study demonstrate that BRG1 plays a significant role in mediating the production of CCL2 in OTSCC cells in response to TNF‐α stimulation. This process involves the cooperative action of acetylated histone and NF‐κB recruitment to the CCL2 promoter site. Our data suggest that BRG1 serves as a critical epigenetic mediator in the regulation of TNF‐α‐induced CCL2 transcription in OTSCC cells.
MAGP2 promotes osteogenic differentiation during fracture healing through its crosstalk with the β‐catenin pathway
Authors: Chen Zhiguang , Zhao Qi , Chen Lianghong , Gao Songlan , Meng Lingshuai , Liu Yingjie , Wang Yu , Li Tiegang , Xue Jinqi
Published: February 2024

Osteogenic differentiation is important for fracture healing. Microfibrial‐associated glycoprotein 2 (MAGP2) is found to function as a proangiogenic regulator in bone formation; however, its role in osteogenic differentiation during bone repair is not clear. Here, a mouse model of critical‐sized femur fracture was constructed, and the adenovirus expressing MAGP2 was delivered into the fracture site. Mice with MAGP2 overexpression exhibited increased bone mineral density and bone volume fraction (BV/TV) at Day 14 postfracture. Within 7 days postfracture, overexpression of MAGP2 increased collagen I and II expression at the fracture callus, with increasing chondrogenesis. MAGP2 inhibited collagen II level but elevated collagen I by 14 days following fracture, accompanied by increased endochondral bone formation. In mouse osteoblast precursor MC3T3‐E1 cells, MAGP2 treatment elevated the expression of osteoblastic factors (osterix, BGLAP and collagen I) and enhanced ALP activity and mineralization through activating β‐catenin signaling after osteogenic induction. Besides, MAGP2 could interact with lipoprotein receptor‐related protein 5 (LRP5) and upregulated its expression. Promotion of osteogenic differentiation and β‐catenin activation mediated by MAGP2 was partially reversed by LRP5 knockdown. Interestingly, β‐catenin/transcription factor 4 (TCF4) increased MAGP2 expression probably by binding to MAGP2 promoter. These findings suggest that MAGP2 may interact with β‐catenin/TCF4 to enhance β‐catenin/TCF4's function and activate LRP5‐activated β‐catenin signaling pathway, thus promoting osteogenic differentiation for fracture repair. mRNA sequencing identified the potential targets of MAGP2, providing novel insights into MAGP2 function and the directions for future research.
Training future leaders: A qualitative study exploring leadership development in predoctoral dental curricula
Authors: Mara Matthew D.
Published: February 2024

Purpose/objective

Commission on Dental Accreditation (CODA) accreditation standard 2‐19 states predoctoral dental schools must assess students’ ability to function successfully as the leader of the oral health care team. This study aimed to explore how dental schools incorporate leadership training into their curriculum to better understand the leadership skills students learn, the ways students engage in leadership training, and the opportunities students have to practice leadership skills with their peers.

Methods

The aim of this 2022 qualitative phenomenology study was to use semi‐structured interviews with academic Deans at CODA‐accredited dental schools and one subject matter expert to uncover types of cognitive, behavioral, and environmental factors influencing leadership training through the lens of social cognitive theory. All interviews were recorded on Zoom, transcribed, de‐identified, and analyzed for recurring themes using NVivo. Eight academic Deans and one subject matter expert participated in the study.

Results

Four major themes emerged from the data: leadership is essential for dental professionals, leadership is incorporated into the curricula in diverse ways, students most often engage in leadership training opportunities with dental peers and interprofessional opportunities could be expanded, and dental schools often face barriers to incorporating leadership training. Vertically integrated case presentations and team‐based practice management simulations are meaningful leadership development activities. Prominent barriers include time constraints, lack of faculty champions with teaching leadership expertise, and prioritizing the development of hand skills.

Conclusion

Standard practices for student leadership development and assessment do not appear to exist across dental school curricula. Findings support the need for a leadership development framework.
Health‐related quality of life and fear of progression in individuals with Li‐Fraumeni syndrome
Authors: Kiermeier Senta , Schott Sarah , Nees Juliane , Dutzmann Christina , Strüwe Farina , Kratz Christian P. , Sauer Christina , Fleischer Anna , Keymling Myriam , Maatouk Imad
Published: February 2024

Li‐Fraumeni syndrome (LFS) is a rare autosomal dominant cancer predisposition syndrome associated with a highly elevated lifetime cancer risk. This and the recommended intense surveillance program represent a large psychological burden on families. In order to develop targeted psychosocial interventions, we conducted a needs assessment. Adults (≥18 years) with LFS were included via regular hospital visits and online support groups and newsletters. Individuals filled out a questionnaire addressing among others: fear of progression (FoP‐questionnaire, short‐form), health‐related quality of life (HRQoL, Short‐Form Health Survey‐12), distress (National Comprehensive Cancer Network distress thermometer), perceived cancer risk, and aspects of surveillance adherence. Collecting data over a 14‐month period (March 2020 – June 2021), 70 adults were recruited (female = 58, 82.9%; mean age = 41.53 years). With mean mental component scores (MCS) of 42.28 (SD = 10.79), and physical component scores (PCS) of 48.83 (SD = 10.46), HRQoL was low in 34.8% (physical) and 59.4% (mental) of individuals when applying a mean cut‐off of 45.4 (PCS) and 47.5 (MCS) to indicate poor HRQoL. High levels of FoP and distress were present in 68.6% and 69.1% of the participants, respectively. Performing a multiple linear regression on MCS and PCS, no sociodemographic variable was shown to be significant. FoP (β = −0.33, p < 0.05) and distress (β = −0.34, p < 0.05) were significantly associated with MCS. Individuals in our sample were burdened more than expected, with the majority reporting low levels of (mental) HRQoL, high distress, and FoP. Psychosocial support is necessary to help individuals with LFS (survivors as well as “previvors”) increase their HRQoL, as it is crucial to survival.
Phlebotomy‐free days in children hospitalized with common infections and their association with clinical outcomes
Authors: Collins Megan E. , Hall Matt , Shah Samir S. , Molloy Matthew J. , Aronson Paul L. , Cotter Jillian M. , Steiner Michael J. , McCoy Elisha , Tchou Michael J. , Stephens John R. , Markham Jessica L.
Published: February 2024

Background

Phlebotomy for hospitalized children has consequences (e.g., pain, iatrogenic anemia), and unnecessary testing is a modifiable source of waste in healthcare. Days without blood draws or phlebotomy‐free days (PFDs) has the potential to serve as a hospital quality measure.

Objective

To describe: (1) the frequency of PFDs in children hospitalized with common infections and (2) the association of PFDs with clinical outcomes.

Design, Settings and Participants

We performed a cross‐sectional study of children hospitalized 2018–2019 with common infections at 38 hospitals using the Pediatric Health Information System database. We included infectious All Patients Refined Diagnosis Related Groups with a median length of stay (LOS) >2 days. We excluded patients with medical complexity, interhospital transfers, those receiving intensive care, and in‐hospital mortality.

Main Outcome and Measures

We defined PFDs as hospital days (midnight to midnight) without laboratory blood testing and measured the proportion of PFDs divided by total hospital LOS (PFD ratio) for each condition and hospital. Higher PFD ratios signify more days without phlebotomy. Hospitals were grouped into low, moderate, and high average PFD ratios. Adjusted outcomes (LOS, costs, and readmissions) were compared across groups.

Results

We identified 126,135 encounters. Bronchiolitis (0.78) and pneumonia (0.54) had the highest PFD ratios (most PFDs), while osteoarticular infections (0.28) and gastroenteritis (0.30) had the lowest PFD ratios. There were no differences in adjusted clinical outcomes across PFD ratio groups. Among children hospitalized with common infections, PFD ratios varied across conditions and hospitals, with no association with outcomes. Our data suggest overuse of phlebotomy and opportunities to improve the care of hospitalized children.