bluuebunny/crossref_metadata_2025 huggingface dataset:
Green extraction and partial purification of roselle (Hibiscus sabdariffa L.) extracts with high amounts of phytochemicals and in vitro antioxidant and antibacterial effects
Authors: Chongwilaikasem Namthip , Sithisarn Patchima , Rojsanga Piyanuch , Sithisarn Pongtip
Published: October 2024

The aim of this study is to develop roselle (Hibiscus sabdariffa L.) extracts with high amounts of phytochemicals and in vitro antioxidant and antibacterial effects using green extraction technique. Roselle extract prepared by ultrasonic extraction with 80% ethanol and 1% hydrochloric acid (RSUEH) promoted the highest yield and high total phenolic (5.21 ± 0.05 g% gallic acid equivalent of dried extract), total flavonoid (1.29 ± 0.06 g% quercetin equivalent of dried extract), and total anthocyanin contents (0.21 ± 0.00 and 0.44 ± 0.00 g% cyanidin 3‐glucoside equivalent of dried extract determined by pH‐differential method with standard calculation and pH‐differential method with standard curve of cyanidin 3‐glucoside, respectively). From the validated high‐performance liquid chromatography analysis, delphinidin‐3‐sambubioside, delphinidin‐3‐glucoside, and cyanidin‐3‐glucoside were found to be the major anthocyanins in roselle extract. This extract exhibited moderate 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) scavenging effect (EC50 289.61 ± 0.16 µg/mL) and strong inhibitory effects against Escherichia coli, Staphylococcus aureus, Staphylococcus intermedius, Proteus mirabilis, and Pseudomonas aeruginosa with the inhibitory concentration (IC50) values in the range of 0.15 ± 0.05 to 4.64 ± 0.07 mg/mL and the minimum inhibitory concentration (MIC) values ranged from 1.66 ± 0.06 to 7.11 ± 1.05 mg/mL. From partial purification, fraction 28 (F28) contained higher amounts of all analyzed phytochemicals than roselle extracts and promoted stronger DPPH scavenging effects (EC50 54.88 ± 2.23 µg/mL). F28 showed antibacterial activity with IC50 values against all tested bacteria in the range of 0.19 ± 0.07 to 4.69 ± 0.09 mg/mL, and the MIC values ranged from 2.46 ± 0.08 to 6.24 ± 0.09 mg/mL.
Effect of NaCl partial replacement by KCl, Ca‐ascorbate, and spent hen meat hydrolysate on the physicochemical properties and quality of Cantonese sausage
Authors: Chen Ruixia , Xiang Junyi , Liu Xiao‐Chen , Yao Xianqi , Tomasevic Igor , Wang Wei , Sun Weizheng
Published: October 2024

A large amount of NaCl is usually used to provide a unique flavor and extend the shelf life of meat products. However, excessive sodium intake may cause diseases such as cardiovascular diseases. Spent hen meat hydrolysate (SHH) as an efficient NaCl substitute was developed with inefficient research related to SHH application in food systems. Therefore, the effects of NaCl replacement with SHH, KCl, and Ca‐ascorbate on the quality of low‐sodium Cantonese sausage were investigated. Four groups of salt formulation, I (100% NaCl), II (NaCl/KCl/Ca‐ascorbate = 60%/30%/10%), III (NaCl/KCl/Ca‐ascorbate/SHH = 50%/30%/10%/10%), and IV (NaCl/KCl/Ca‐ascorbate/SHH = 30%/30%/10%/30%), were used to produce Cantonese sausages. The moisture and nitrite content decreased, the microbiological growth was inhibited, and the protein content increased after adding SHH for Cantonese sausages with NaCl substitution degrees of 50% and 70%. The saltiness, overall flavor, color, and texture of low‐sodium Cantonese sausages with SHH were maintained or improved compared to the Cantonese sausage without sodium replacement. The proportion of peptides with molecular weight <1 kDa in Cantonese sausages increased after adding SHH, which may improve the overall flavor by interacting with peptides or other compounds. SHH combined with KCl and Ca‐ascorbate is an efficient NaCl substitute, which can maintain and even improve Cantonese sausage quality and reduce sodium content up to 70%. These findings offer a promising reference for SHH application in the food industry and promote the development of salt taste–enhancing hydrolysate in food science.
Assessment of quality and antioxidant capacity of peach in response to different UV‐C dose irradiation
Authors: Han Shuai , Wang Xu , Cong Haihua , Wu Youzhi , Cai Hongfang
Published: October 2024

The effects of different doses of UV‐C irradiation (0, 0.5, 1.0, 2.0, and 4.0 kJ m−2) on the quality and antioxidant capacity of peach fruit were examined. Results showed that irradiation at 2.0 kJ m−2 led to higher firmness and total soluble solids, as well as lower weight loss and decay index. Additionally, peach fruits irradiated with 2.0 kJ m−2 UV‐C exhibited increased production of reactive oxygen species, which in turn stimulated the synthesis of total phenolics and total flavonoids and enhanced the activities of superoxide dismutase, catalase, peroxidase, and ascorbate peroxidase. Overall, the best abiotic stress effect was observed with 2.0 kJ m−2 UV‐C irradiation, resulting in improved shelf quality and increased antioxidant capacity of peach fruits during storage.

Practical Application

This study provides a theoretical basis for the application of UV‐C irradiation in peach fruit preservation.
Cultivating complexity: Advancements in establishing in vitro models for the mucus‐adhering gut microbiota
Authors: Calvigioni Marco , Mazzantini Diletta , Celandroni Francesco , Vozzi Giovanni , Ghelardi Emilia
Published: October 2024

A healthy mucus is essential for maintaining intestinal homeostasis and overall well‐being. In recent years, extensive research focused on understanding the intricate interactions between mucus and the gut microbiota. Mucus‐adhering bacteria play crucial roles in preserving barrier integrity, epithelial permeability and mucus architecture, as well as in the colonization resistance against pathogens. Unravelling the significance of these microorganisms in human health and disease is challenging, primarily because most of the studies on the human gut microbiota rely on faecal samples, which do not fully represent the microecological complexity found in the intestinal mucosa. This review discusses novel strategies to specifically target and evaluate the mucosal microbiota, such as culturomics applied to mucosal biopsies or brushings, intestinal organoids and artificial in vitro models incorporating mucus.
Luteinizing hormone is independently associated with high‐sensitive cardiac troponin T elevation in postmenopausal T2DM patients: A cross‐sectional study
Authors: Wang Yahao , Li Yixuan , Liu Chuanfeng , Wang Yangang , Li Yiming
Published: October 2024

Background

It is known that the risk of ischemic heart disease increases in patients with type 2 diabetes mellitus (T2DM). For female patients, the incidence of heart disease can be even greater after menopause, accompanied by dramatic changes in sex hormones. We investigated the correlations between sex hormones and markers of ischemic heart diseases in postmenopausal females with T2DM patients.

Methods

This cross‐sectional study collected data from 324 hospitalized postmenopausal females with T2DM. Multiple linear regression analyses were conducted to determine the correlations between sex hormones and cardiac markers including high‐sensitive cardiac troponin T (hs‐cTnT) and N‐terminal prohormone of brain natriuretic peptide (NT‐proBNP) levels.

Results

Multiple linear regression analyses revealed that luteinizing hormone (LH) was positively and independently associated with hs‐cTnT concentrations in postmenopausal females with T2DM (β = 0.189, p = 0.002). Postmenopausal females with T2DM and subclinical myocardial injury had higher LH levels than those without subclinical myocardial injury (29.67 vs. 25.08 mIU/mL, p < 0.001). A multivariate logistic regression analysis confirmed an independent and significant association between elevated LH and subclinical myocardial injury in postmenopausal females with T2DM (adjusted odds ratio [OR] = 1.077, 95% confidence interval [CI], 1.033–1.124; p < 0.001). As another gonadotropin, the follicle‐stimulating hormone did not show independent correlations with hs‐cTnT or NT‐proBNP (p > 0.05). Neither estrogen nor testosterone was correlated with cardiac markers.

Conclusions

Elevated LH levels were positively and independently associated with increased hs‐cTnT levels in postmenopausal women with T2DM. Our findings suggest that LH could serve as a potential marker for assessing the risk of subclinical myocardial injury in postmenopausal females with T2DM.

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Protective effect of regular physical activity against diabetes‐related lower extremity amputation
Authors: Kim Jae Won , Han Kyung‐Do , Kim Jun Hyeok , Lee Yoon Jae
Published: October 2024

Background

Foot ulcers are a major complication of diabetes mellitus that increase morbidity and mortality in patients with diabetes, affect their quality of life, and increase the overall social burden. A considerable number of patients with diabetic foot ulcers (DFUs) require amputations every year.

Methods

This nation population–based study included 1 923 483 patients with diabetes who underwent regular health screening through the National Health Insurance Service during January 2009 and December 2012. We investigated the association between changes in physical activity (PA) status and the incidence of lower extremity amputation (LEA). Based on changes in PA status, participants were categorized into four groups: “remained inactive,” “remained active,” “active‐to‐inactive,” and “inactive‐to‐active.”

Results

Regular PA is an independent factor associated with a decreased risk of LEA in patients with diabetes. During the follow‐up period, 0.23% (n = 4454) of the patients underwent LEA. Compared with the “remained inactive” group, the “remained active” group were at the lowest risk of LEA (adjusted hazard ratio 0.5888; 95% confidence interval 0.524–0.66). A protective effect of regular PA against LEA was observed in the “remaining active” group.

Conclusions

Our findings suggest a protective role of PA against LEA in individuals with diabetes. This highlights the importance of recommending appropriate levels of PA for patients with diabetes. The study also showed a dose–response relationship, indicating that engaging in vigorous‐intensity PA was most beneficial, and higher amounts of PA may provide additional benefits.

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The potential adverse effects of hypodermic glucagon‐like peptide ‐1 receptor agonist on patients with type 2 diabetes: A population‐based study
Authors: Cheng Zhiyuan , Wang Shuang , Li Fu‐rong , Jin Cheng , Mo Chunbao , Zheng Jing , Li Xia , Liang Fengchao , Yang Jinkui , Gu Dongfeng
Published: October 2024

Background

Glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs), a class of injectable antidiabetic drugs, have shown significant efficacies in improving glycemic and weight control in patients with type 2 diabetes (T2D). However, the long‐term safety of GLP‐1 RAs remains insufficiently studied. This study aimed to provide real‐world evidence on potential adverse outcomes associated with GLP‐1 RAs use in T2D patients without major chronic diseases including impaired cardiac or renal function.

Methods

We conducted a retrospective cohort study involving 7746 T2D patients on GLP‐1 RAs in Shenzhen, China. They were compared with 124 371 metformin‐only users and 36 146 insulin‐only users, forming two therapy control groups. GLP‐1 RAs users were also further 1:2 paired with the control groups. Competing risk survival analyses were conducted to assess the incidence risks, presenting subdistributional hazard ratios (sHRs) with 95% confidence intervals (CIs) for various adverse outcomes associated with GLP‐1 RAs use.

Results

Compared with metformin‐only users, GLP‐1 RAs use was associated with increased risks of various adverse outcomes (sHRs with 95% CIs), including pancreatitis (2.01, 1.24–3.24), acute nephritis (3.20, 2.17–4.70), kidney failure (3.73, 2.74–5.08), thyroid cancer (2.25, 1.23–4.10), and thyroid dysfunction (1.27, 1.00–1.63), respectively; Similar results were also found when compared with insulin‐only users. Importantly, long‐term (≥12 months) GLP‐1 RAs use may further elevate the incidence risks of pancreatitis, acute nephritis, thyroid cancer, and thyroid dysfunction.

Conclusion

Compared with traditional T2D treatments, GLP‐1 RAs use may be associated with increased risks of various adverse outcomes in a Chinese population. Cautions were strongly warranted in the use of GLP‐1 RAs. Further validation is crucial across diverse populations.

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Three Novel Spider Genomes Unveil Spidroin Diversification and Hox Cluster Architecture: Ryuthela nishihirai (Liphistiidae), Uloborus plumipes (Uloboridae) and Cheiracanthium punctorium (Cheiracanthiidae)
Authors: Schöneberg Yannis , Audisio Tracy Lynn , Ben Hamadou Alexander , Forman Martin , Král Jiří , Kořínková Tereza , Líznarová Eva , Mayer Christoph , Prokopcová Lenka , Krehenwinkel Henrik , Prost Stefan , Kennedy Susan
Published: October 2024

Spiders are a hyperdiverse taxon and among the most abundant predators in nearly all terrestrial habitats. Their success is often attributed to key developments in their evolution such as silk and venom production and major apomorphies such as a whole‐genome duplication. Resolving deep relationships within the spider tree of life has been historically challenging, making it difficult to measure the relative importance of these novelties for spider evolution. Whole‐genome data offer an essential resource in these efforts, but also for functional genomic studies. Here, we present de novo assemblies for three spider species: Ryuthela nishihirai (Liphistiidae), a representative of the ancient Mesothelae, the suborder that is sister to all other extant spiders; Uloborus plumipes (Uloboridae), a cribellate orbweaver whose phylogenetic placement is especially challenging; and Cheiracanthium punctorium (Cheiracanthiidae), which represents only the second family to be sequenced in the hyperdiverse Dionycha clade. These genomes fill critical gaps in the spider tree of life. Using these novel genomes along with 25 previously published ones, we examine the evolutionary history of spidroin gene and structural hox cluster diversity. Our assemblies provide critical genomic resources to facilitate deeper investigations into spider evolution. The near chromosome‐level genome of the ‘living fossil’ R. nishihirai represents an especially important step forward, offering new insights into the origins of spider traits.
An aggregative approach to pricing equilibrium among multi‐product firms with nested demand
Authors: Garrido Francisco
Published: October 2024

I show equilibrium existence for a price‐setting game among multi‐product firms facing a nested logit/CES demand. As opposed to previous research I allow arbitrary firm/nest overlap, making the result relevant for applied work. Additionally, under easy‐to‐verify conditions, I show that there exist extreme equilibria, which are the most and least preferred by consumers, and provide an algorithm to find them. This allows researcher to numerically verify equilibrium uniqueness in applications, that is, if the extreme equilibria are equal to each other. As a by‐product, I show that inverting FOCs correctly identifies the marginal costs that rationalize observed prices.
Bank relationship and contractual flexibility: Evidence from covenant enforcement
Authors: Gam Yong Kyu , Liu Chunbo
Published: October 2024

This paper investigates how banks utilize soft information to provide contractual flexibility in loan covenant enforcement. We find that relationship lenders are significantly less likely than non‐relationship lenders to enforce covenants for material violations when borrowers are potentially in breach of financial covenants. The mitigation of information asymmetry by relationship lending, as opposed to alternative explanations, serves as the underlying mechanism. Furthermore, relationship borrowers with potential covenant breaches are less likely to experience increases in loan interest rates after renegotiation, to adopt conservative financial or investment policies, or to file for bankruptcy. Following potential covenant breaches of borrowers, relationship banks are better able to preserve regulatory capital and secure future lending business. Our findings suggest that soft information accumulated during lending relationships is vital for banks to provide contractual flexibility.
Intragenic duplication disrupting the reading frame of MFSD8 in Small Swiss Hounds with neuronal ceroid lipofuscinosis
Authors: Rietmann Stefan J. , Loderstedt Shenja , Matiasek Kaspar , Kiefer Ingmar , Jagannathan Vidhya , Leeb Tosso
Published: October 2024

Neuronal ceroid lipofuscinosis (NCL) represents a heterogenous group of lysosomal storage diseases resulting in progressive neurodegeneration. We investigated two Small Swiss Hound littermates that showed progressive ataxia and loss of cognitive functions and vision starting around the age of 12 months. Both dogs had to be euthanized a few months after the onset of disease owing to the severity of their clinical signs. Pathological investigation of one affected dog revealed cerebral and cerebellar atrophy with cytoplasmic accumulation of autofluorescent material in degenerating neurons. The clinical signs in combination with the characteristic histopathology led to a tentative diagnosis of NCL. In the subsequent genetic investigation, the genome of one affected dog was sequenced. This revealed a duplication of 18 819 bp within the MFSD8 gene. The duplication breakpoints were located in intron 3 and exon 12 of the gene and were predicted to disrupt the reading frame. Both affected dogs carried the duplication in a homozygous state and there was perfect cosegregation of the genotypes with the phenotype in a large pedigree, consistent with autosomal recessive inheritance. MFSD8 loss‐of‐function variants are a known cause of NCL7 in human patients, dogs and other mammalian species. The existing knowledge on MFSD8 together with the experimental data strongly suggests that the identified intragenic MFSD8 duplication caused the disease in the Small Swiss Hounds. These results allow their diagnosis to be refined to NCL7 and enable genetic testing in the breed to avoid further unintentional carrier × carrier matings.
An experimental approach to farmer valuation of African rice genetic resources
Authors: Tyack Nicholas , Arouna Aminou , Aboudou Rachidi , Ndjiondjop Marie Noelle
Published: October 2024

Genebanks serve as both providers of valuable traits for breeding programs and repositories of diverse crop genetic material representing society's agricultural heritage. In this study, we use a Becker‐DeGroot‐Marschak mechanism to elicit the willingness‐to‐pay of rice farmers in Côte d'Ivoire for small amounts of African rice (Oryza glaberrima) landraces held by the genebank of the Rice Biodiversity Center for Africa, and for seed of newly developed ARICA rice varieties bred using genebank materials. Using a field experiment, we additionally investigate how randomized exposure to and experimentation with small amounts of African rice landrace seed or seed of advanced rice varieties developed by AfricaRice affect how smallholder rice farmers value these novel genetic resources. Surprisingly, we find that farmers generally value having access to African rice landraces at approximately the same level as for advanced rice varieties (and far above market rates for improved seed), and that those farmers who grew landrace seed in the offseason were willing to pay more than those who did not. Our results demonstrate the additional value provided by the conservation of African rice landrace varieties (apart from their use in breeding) and highlight the importance of experimentation in the adoption process.
Pyodermatitis vegetans confined to the umbilicus: Report of 2 cases
Authors: Matsumura Natsuko , Hiraiwa Tomoko , Yamamoto Toshiyuki
Published: October 2024

Pyodermatitis pyostomatitis vegetans is a rare variant of neutrophilic disorders, affecting the intertriginous areas such as axilla and groin, umbilicus, as well as the oral mucosa. We herein describe 2 female patients, in both of whom the umbilicus was restrictedly involved.
Association Between Maternal Cytomegalovirus Seropositivity, Preterm Birth, and Preeclampsia in Two Cohorts From Quebec, Canada: A Mediation Analysis
Authors: Balegamire Safari Joseph , Mâsse Benoît , Audibert François , Lamarre Valerie , Giguere Yves , Forest Jean‐Claude , Boucoiran Isabelle
Published: October 2024

Problem

Preterm birth and preeclampsia significantly contribute to infant morbidity and mortality, posing critical public health concerns. Viral infections, particularly Cytomegalovirus (CMV), associated with chronic inflammation, may play a role in these adverse pregnancy outcomes. The contribution of CMV to preterm birth and preeclampsia requires further investigation.

Method of Study

Data from 6048 pregnant women from two prospective Quebec cohorts, recruited between May 2005 and August 2012, were analyzed. First‐trimester CMV serology was the exposure variable. Associations were assessed using multivariable logistic regression adjusted by inverse probability treatment weighting (IPTW) of propensity scores. Mediation analyses estimated the direct effect of maternal CMV serostatus on preterm birth, excluding mediation by preeclampsia.

Results

Preterm birth and preeclampsia proportions were 5.1% (95% CI: 4.6–5.7) and 1.9% (95% CI: 1.6–2.3), respectively. Multivariable logistic regression adjusted by IPTW showed associations between CMV seropositivity and preterm birth (OR 1.20, 95% CI: 1.02–1.41) and CMV seropositivity and preeclampsia (OR 1.41, 95% CI: 1.08–1.84). Mediation analysis indicated that 97% of the total effect of CMV seropositivity on preterm birth is direct, with the remaining 3% mediated by preeclampsia.

Conclusions

CMV seropositivity appears to be a risk factor for both preterm birth and preeclampsia. The effect of maternal CMV seropositivity on preterm birth is primarily direct, not mediated by preeclampsia. Future studies should explore the impact of preventive measures against CMV infection on the incidence of preterm delivery and preeclampsia.
National survey found that paediatricians frequently used messaging apps to hold informal consultations with parents and patients
Authors: Goffer Yonatan , Levinsky Yoel , Landau Daniel , Berger Itay , Vardy Yoav , Chodick Gabriel , Lowenthal Alexander , Ashkenazi‐Hoffnung Liat , Scheuerman Oded
Published: October 2024

Aim

Paediatricians using instant messaging phone apps for informal medical discussions poses ethical and legal risks. We filled a gap in the research, by assessing the use of apps and the possible risks.

Methods

A national, cross‐sectional, questionnaire study was conducted in Israel from 11 August to 20 November 2019. The frequency of informal discussions, clinical details and recommendations were compared to the paediatricians' expertise and work settings. The discussions included work and private phones, consultation with the parents of patients and advice to the paediatricians' friends and families.

Results

The 305 paediatricians who responded had a median age of 37 (range 27–74) years: 42% were residents and 58% were specialists. The majority (99%) had carried out informal discussions using a messaging app in the last week and 65% had used them for 1–5 discussions. Specialists were more likely to use apps for more than 10 discussions per week than residents (24% vs. 5%, p < 0.001) and recommend treatment via apps (35% vs. 22%, p < 0.001). A third failed to provide disclaimers about the risks of app‐based discussions.

Conclusion

Using instant messaging apps for informal medical discussions was common, but ethical and legal aspects were not always fully considered.
The multiple patterns of factional influence: Evidence from the 2021 LDP presidential election
Authors: Asano Masahiko , Patterson Dennis
Published: October 2024

Traditionally, factions and seniority determined who became President of the Liberal Democratic Party (LDP) and, thus, Japan's Prime Minister. Since the electoral reform of 1994, however, some scholars have argued that the role of factions has declined, and this has led to ongoing debates over the extent to which factions and other factors have helped determine who will become the leader of Japan's LDP. Using data from the 2021 LDP Presidential election, we find that it is not policy but factional affiliations that matter for LDP members in selecting their leader. In addition to this finding, we disaggregate faction and show that the influence of this political institution in LDP Presidential elections varies across different factions. We also find that electorally weaker LDP incumbents are more likely to support a candidate who is more popular among Japanese voters in general.
Avatrombopag for the treatment of patients with chemotherapy‐induced thrombocytopenia: A case series
Authors: Galamaga Robert , Johnston Stephanie , Acosta Cassaundra
Published: October 2024

Management of chemotherapy‐induced thrombocytopenia (CIT) is challenging, often resulting in chemotherapy treatment delays, dose reduction, and treatment interruption. Randomized trials support the potential efficacy and safety of thrombopoietin receptor agonists in CIT management. A phase III trial of avatrombopag (AVA) demonstrated increased platelet counts (PC) in patients with solid tumours experiencing CIT. To complement those findings, this case series of six patients with solid tumours and CIT is presented. Results from these cases support the clinical benefit of AVA in improving PC and reducing the impact of CIT on tumour treatment, allowing continued therapy without dose reduction or treatment interruption.
P2RY6 deletion promotes UVB‐induced skin carcinogenesis by activating the PI3K/AKT signal pathway
Authors: Xu Peng , Liu Tanglin , Yang Zile , Zang Kai , Gao Xiaoxuan , Shi Yuling , Ye Xiyun , Dang Yongyan
Published: October 2024

Our previous research has demonstrated that P2RY6 functions as an oncogene in DMBA/TPA‐induced two‐stage chemical skin carcinogenesis in mice. However, considering that human skin cancer is predominantly attributed to UV radiation from sunlight, additional investigations are needed to elucidate the role of P2RY6 in UVB‐induced skin carcinogenesis. Surprisingly, we found that P2ry6‐deficient mice exhibited marked promotion to UVB‐induced skin papilloma formation compared with wild‐type mice, suggesting its tumor‐suppressive role in UVB‐induced skin cancer. Additionally, a P2ry6 gene knockout promoted skin hyperplasia induced by short‐term UVB irradiation, while UDP, the ligand of P2RY6, could inhibit the short‐term UVB‐induced increase of epiderma thickness in mouse skin. Furthermore, UVB irradiation could significantly upregulate P2RY6 expression in human and mouse skin cells. These results indicated that P2RY6 may play a crucial protective role in resisting the UVB‐induced formation of skin tumors. At the molecular level, the loss of the P2RY6 gene inhibits the ubiquitination modification and expression of XPC after UVB irradiation in skin keratinocytes, resulting in the accumulation of CPDs (cyclobutane pyrimidine dimers). We have also demonstrated that P2RY6 deletion activates the PI3K/AKT signaling pathway both in vitro and in vivo. The CPD accumulation and acute inflammatory response enhanced by the loss of the P2RY6 gene can be reversed by an AKT inhibitor. These findings suggest that P2RY6 may act as a tumor suppressor in UVB‐induced skin cancer by regulating the PI3K/AKT signaling pathway.
RNU4‐2‐Related Neurodevelopmental Disorder Is Associated With a Recognisable Facial Gestalt
Authors: Rosenblum Jessica , Beysen Diane , Jansen Anna C. , De Rademaeker Marjan , Reyniers Edwin , Janssens Katrien , Meuwissen Marije
Published: October 2024

De novo heterozygous variants in RNU4‐2, a component of the major spliceosome, were recently found to cause a novel neurodevelopmental disorder. Preliminary evidence suggests that this newly discovered syndrome is one of the most common monogenic causes of neurodevelopmental disorders. It is characterised by developmental delay and intellectual disability, microcephaly, short stature and hypotonia. However, much remains to be elucidated regarding the phenotype of the affected individuals. We report on four novel individuals affected by the condition, two of which were identified following targeted sequencing based solely on the facial features that were similar to those of the first patient we identified. This strongly suggests that this syndrome entails a recognisable morphological phenotype, which is particularly relevant for resource‐limited regions where whole genome sequencing is not readily available, and in view of retro‐active selection/prioritisation of individuals with hitherto negative genetic testing.
Utility of Optical Genome Mapping in Repeat Disorders
Authors: Mutlu Mehmet Burak , Karakaya Taner , Çelebi Hamide Betül Gerik , Duymuş Fahrettin , Seyhan Serhat , Yılmaz Sanem , Yiş Uluç , Atik Tahir , Yetkin Mehmet Fatih , Gümüş Hakan
Published: October 2024

Genomic repeat sequences are patterns of nucleic acids that exist in multiple copies throughout the genome. More than 60 Mendelian disorders are caused by the expansion or contraction of these repeats. Various specific methods for determining tandem repeat variations have been developed. However, these methods are highly specific to the genomic region being studied and sometimes require specialized tools. In this study, we have investigated the use of Optical Genome Mapping (OGM) as a diagnostic tool for detecting repeat disorders. We evaluated 19 patients with a prediagnosis of repeat disorders and explained the molecular etiology of 9 of them with OGM (5 patients with Facioscapulohumeral Muscular Dystrophy (FSHD), 2 patients with Friedreich's Ataxia (FA), 1 patient with Fragile X Syndrome (FXS), and 1 patient with Progressive Myoclonic Epilepsy 1A (EPM1A)). We confirmed OGM results with more widely used fragment analysis techniques. This study highlights the utility of OGM as a diagnostic tool for repeat expansion and contraction diseases such as FA, FXS, EPM1A, and FSHD.
A Novel PTPRQ c.3697del Variant Causes Autosomal Dominant Progressive Hearing Loss in Both Humans and Mice
Authors: Zhou Yaqi , Yin Na , Ji Lingchao , Lu Xiaochan , Yang Weiqiang , Ye Weiping , Du Wenhui , Li Ya , Hu Hongyi , Mei Xueshuang
Published: October 2024

PTPRQ plays an important role in the development of inner ear hair cell stereocilia. While many autosomal recessive variants in PTPRQ have been identified as the pathogenic cause for nonsyndromic hearing loss (DFNB84A), so far only one autosomal dominant PTPRQ variant, c.6881G>A (p.Trp2294*), has been reported for late‐onset, mild‐to‐severe hearing loss (DFNA73). By using targeted next‐generation sequencing, this study identified a novel PTPRQ truncating pathogenic variant, c.3697del (p.Leu1233Phefs*11), from a Chinese Han family that co‐segregated with autosomal dominant, postlingual, progressive hearing loss. A Ptprq‐3700del knock‐in mouse model was generated by CRISPR‐Cas9 and characterized for its hearing function and inner ear morphology. While the homozygous knock‐in mice exhibit profound hearing loss at all frequencies at the age of 3 weeks, the heterozygous mutant mice resemble the human patients in mild, progressive hearing loss from age 3 to 12 weeks, primarily affecting high frequencies. At this stage, the homozygous knock‐in mice have a normal hair cell count but disorganized stereocilia. Cochlear proteosome analysis of the homozygous mutant mice revealed differentially expressed genes and pathways involved in oxidative phosphorylation, regulation of angiogenesis and synaptic vesicle cycling. Our study provides a valuable animal model for further functional studies of the pathogenic mechanisms underlying DFNA73.
Gamma‐glutamyl transferase: A potential biomarker for pancreas steatosis in patients with concurrent obesity, insulin resistance and metabolic dysfunction‐associated steatotic liver disease
Authors: Chiyanika Chileka , Shumbayawonda Elizabeth , Pansini Michele , Liu Kin Hung , Yip Terry Cheuk‐Fung , Wong Vincent Wai‐Sun , Chu Winnie Chiu Wing
Published: October 2024

To evaluate the relationship between serum gamma‐glutamyl transferase (GGT) levels and fatty pancreas in subjects with concurrent obesity, insulin resistance and metabolic dysfunction‐associated steatotic liver disease (MASLD) without a history of pancreatitis. From March 2019 to September 2021, 31 adult subjects with concurrent obesity and MASLD were recruited as part of the study investigating the biological impact of bariatric surgery and lifestyle modification on obesity. Chemical shift encoded MRI of the abdomen, LiverMultiScan, anthropometric, clinical and blood biochemistry analyses were performed prior to any intervention at baseline. GGT (p <.001) was significantly different between those ‘with fatty pancreas’ and ‘without fatty pancreas’ groups. GGT (p <.001) was significantly different between those ‘with both metabolic syndrome and fatty pancreas’ and those ‘with metabolic syndrome but without fatty pancreas.’ GGT (p <.001) was also significantly different between those ‘with both diabetes and fatty pancreas’ and those ‘with diabetes but without fatty pancreas’. Logistic regression analysis showed that abnormal GGT levels (p = .010) and Hypertension (p = .045) were significant independent predictors of fatty pancreas. GGT was associated with fatty pancreas by an odds ratio 7.333 (95% [CI]: 1.467–36.664), while the AUROC of GGT in determining fatty pancreas was 0.849. Elevation in serum GGT might be a potential marker to identify fatty pancreas.
A spatially explicit assessment of factors shaping attitudes toward African elephant conservation
Authors: Carroll Sarah L. , Vogel Susanne M. , Taek Purity Nititi , Tumuti Clevers , Vasudev Divya , Goswami Varun R. , Wall Jake , Mwiu Stephen , Reid Robin S. , Salerno Jonathan
Published: October 2024

Conservation plans that explicitly account for the social landscape where people and wildlife co‐occur can yield more effective and equitable conservation practices and outcomes. Yet, social data remain underutilized, often because social data are treated as aspatial or are analyzed with approaches that do not quantify uncertainty or address bias in self‐reported data. We conducted a survey (questionnaires) of 177 households in a multiuse landscape in the Kenya–Tanzania borderlands. In a mixed‐methods approach, we used Bayesian hierarchical models to quantify and map local attitudes toward African elephant (Loxodonta africana) conservation while accounting for response bias and then combined inference from attitude models with thematic analysis of open‐ended responses and cointerpretation of results with local communities to gain deeper understanding of what explains attitudes of people living with wildlife. Model estimates showed that believing elephants have sociocultural value increased the probability of respondents holding positive attitudes toward elephant conservation in general (mean increase = 0.31 [95% credible interval, CrI, 0.02–0.67]), but experiencing negative impacts from any wildlife species lowered the probability of respondents holding a positive attitude toward local elephant conservation (mean decrease = −0.20 [95% CrI −0.42 to 0.03]). Qualitative data revealed that safety and well‐being concerns related to the perceived threats that elephants pose to human lives and livelihoods, and limited incentives to support conservation on community and private lands lowered positive local attitude probabilities and contributed to negative perceptions of human–elephant coexistence. Our spatially explicit modeling approach revealed fine‐scale variation in drivers of conservation attitudes that can inform targeted conservation planning. Our results suggest that approaches focused on sustaining existing sociocultural values and relationships with wildlife, investing in well‐being, and implementing species‐agnostic approaches to wildlife impact mitigation could improve conservation outcomes in shared landscapes.
Histological and photoacoustic evaluation of rectal cancer after neoadjuvant therapy using microvascular density
Authors: Eltahir Ahmed A. , Nie Haolin , Kou Sitai , Marolt Clayton , Navale Pooja , Mutch Matthew G. , Chapman William C. , Zhu Quing
Published: October 2024

Aim

As non‐operative management of rectal cancer proliferates, re‐staging and surveillance methods are critical in selecting appropriate patients for organ preservation versus proctectomy. In previous work, the authors have shown that transrectal acoustic resolution photoacoustic microscopy (ARPAM) co‐registered with ultrasound can differentiate residual cancer from complete tumoural response to neoadjuvant therapy. We hypothesize that these findings are due to changes in microvascular density (MVD).

Methods

Patients with rectal adenocarcinoma who underwent neoadjuvant therapy, transrectal photoacoustic imaging and resection were included. We first compared immunohistochemical staining with erythroblast transformation‐specific‐related gene (ERG) immunostain to standard CD31 to confirm adequate identification of endothelium. Tissue sections from identical blocks were stained with CD31 and ERG, and then a correlation was calculated between manually labelled CD31‐stained vessels and ERG nuclei density. Second, representative tissue blocks from responders, partial responders and non‐responders were stained with ERG. ERG nuclei density was quantified as a proxy for MVD.

Results

CD31 MVD and ERG nuclei density were strongly correlated (R2 = 0.87; P < 0.01). In the tumour bed of patients after neoadjuvant therapy, MVD of complete responders (599 nuclei/mm2; 95% CI 434–764) is significantly higher (P < 0.01) than that of partial responders (185 nuclei/mm2; 95% CI 64–306) and non‐responders (117 nuclei/mm2; 95% CI 42–192). No significant difference was found between the partial responders and non‐responders (P = 0.60).

Conclusion

Microvascular density appears highest in cases of complete tumour response to neoadjuvant therapy, similar to normal rectal tissue. The histological microvascular patterns seen in treated tissue may explain the imaging patterns seen in photoacoustic microscopy.
A Benchmark Proposal for Non‐Generative Fair Adversarial Learning Strategies Using a Fairness‐Utility Trade‐off Metric
Authors: de Lima Luiz Fernando F. P. , Ricarte Danielle Rousy D. , Siebra Clauirton A.
Published: October 2024

AI systems for decision‐making have become increasingly popular in several areas. However, it is possible to identify biased decisions in many applications, which have become a concern for the computer science, artificial intelligence, and law communities. Therefore, researchers are proposing solutions to mitigate bias and discrimination among decision‐makers. Some explored strategies are based on GANs to generate fair data. Others are based on adversarial learning to achieve fairness by encoding fairness constraints through an adversarial model. Moreover, it is usual for each proposal to assess its model with a specific metric, making comparing current approaches a complex task. Therefore, this work proposes a systematical benchmark procedure to assess the fair machine learning models. The proposed procedure comprises a fairness‐utility trade‐off metric (), the utility and fairness metrics to compose this assessment, the used datasets and preparation, and the statistical test. A previous work presents some of these definitions. The present work enriches the procedure by increasing the applied datasets and statistical guarantees when comparing the models' results. We performed this benchmark evaluation for the non‐generative adversarial models, analyzing the literature models from the same metric perspective. This assessment could not indicate a single model which better performs for all datasets. However, we built an understanding of how each model performs on each dataset with statistical confidence.
Leveraging how animals learn in conservation science: Behavioral responses of reintroduced bison to management interventions
Authors: Verzuh Tana L. , Heuer Karsten , Merkle Jerod A.
Published: October 2024

Reintroduction programs have increased amid unprecedented biodiversity loss, yet the success of these programs lag. A prominent reason for program failure is dispersal beyond the planned range of the population. Management techniques, such as hazing, can be used to prevent movement beyond set boundaries, but to be effective long‐term, the animals must learn to avoid the areas where they are hazed. Although concepts of animal learning have been used to improve reintroduction programs, learning is not often explicitly tested or used as an indicator of program success. We used a conservation behavior framework to evaluate how a range of management techniques influenced learning in a reintroduced population of bison in Banff National Park, Canada. We hypothesized exposure to stronger negative stimuli would enhance learning, leading to more pronounced behavioral responses. Specifically, we tested the degree to which management actions (i.e., drift fence encounters, foot, horseback, helicopter, and combined hazing) elicited behavioral responses and how they facilitated learning. Consistent with our predictions, drift fence interactions and foot and horseback hazing elicited fewer behavioral responses of a smaller magnitude than helicopter hazing or combined methods, suggesting these techniques cause less disturbance to the bison. Bison continually returned to locations where they encountered management actions that caused the least disturbance, demonstrating a lack of associative learning. Bison appeared to form negative associations with locations where they were hazed via helicopter or combined methods, however, and rarely returned to these locations. Evaluating management techniques is essential for improving conservation success. We demonstrate that by bridging the fields of conservation biology and animal learning, we can understand how management techniques influence learning and behavior thereby facilitating effective conservation plans that incorporate disruption levels of the animals, financial costs, and overall effectiveness. Effective conservation plans, in turn, improve our likelihood of successfully managing and recovering species.
Evaluation of Single Versus Two‐Dose Basiliximab Induction Therapy in Live‐Donor Liver Transplant
Authors: Herrmann Benjamin N. , Moore Cody A. , Johnson Heather J. , Humar Abhinav , Shimko Kristen A.
Published: October 2024

Background

Basiliximab is a high‐cost induction agent typically given as two doses in liver transplant recipients. This study evaluated renal outcomes in live‐donor liver transplant recipients (LDLTRs) with stable renal function at the time of transplant receiving one versus two doses of basiliximab.

Methods

We retrospectively identified 231 adult LDLTR with a serum creatinine (SCr) <1.5 mg/dL on post‐transplant Day 5. The primary endpoint was a change in SCr from post‐transplant Days 5 to 30 between the groups. Secondary endpoints included incidence of acute kidney injury (AKI), liver rejection, and culture‐positive infections within 3 and 6 months of transplant. Basiliximab‐related cost savings were also evaluated.

Results

Median change in SCr from post‐transplant Days 5 to 30 was no different between the single‐dose or two‐dose groups (0.1 [IQR: −0.1–0.3] vs. 0.2 [IQR: −0.1–0.4], p = 0.08). Incidence of AKI was 56.9% in the two‐dose group versus 39.0% in the single‐dose group (p = 0.01). There was no difference in bacterial (p = 0.40), fungal (p = 0.59), or viral (p = 0.78) infections. Acute cellular rejection through 6 months post‐transplant was noted in 9.7% of patients receiving two doses and 6.3% in the single‐dose arm (p = 0.42). Basiliximab‐related cost savings in the single‐dose arm was ∼$697 863.72 over 159 transplants.

Conclusions

Single‐dose basiliximab appears to be safe and effective in place of two doses in LDLTR with stable renal function on post‐transplant Day 5. Utilization of a single basiliximab dose significantly reduced medication‐related costs.
Compound Follicles in Folliculitis Decalvans Do Not Contain Vellus and Retained Telogen Follicles—A Pilot Histopathologic Series on Polytrichia
Authors: Lee Juwon , Miteva Mariya
Published: October 2024

Background

Polytrichia is a common clinical and trichoscopic feature in folliculitis decalvans (FD) that morphologically corresponds to compound follicular structures (CFS) of six or more follicles sharing a single infundibulum, surrounded by fibrosis.

Objectives

To characterize the type of follicles in the CFS in scalp biopsy specimens from FD.

Methods

We retrospectively reviewed 10 scalp biopsy specimens obtained by using the trichoscopy‐guided approach from the affected scalp of patients diagnosed with early‐stage FD between 2018 and 2023. We assessed the number and type of follicles within the CFS on horizontal sections.

Results

The total number of assessed follicles was 205, out of which 159 were part of CFS. Of those, 156 were terminal follicles (146 anagen and ten telogen), three intermediate, and zero vellus follicles. Other common findings included dense mixed cell infiltrate consisting of histiocytes, plasma cells, lymphocytes, neutrophils, and eosinophils; psoriasiform hyperplasia; and fragmented hair shafts.

Conclusions

We show that CFS in FD are composed largely of terminal anagen follicles. This may help with further understanding of the disease.
Pricing in response to new information: The case of betting markets
Authors: Fischer Kai , Schmal W. Benedikt
Published: October 2024

Markets are information aggregators. But how do they incorporate new data into their pricing? We examine the response of prediction markets to a novel information shock in a quasi‐natural experiment: How did the absence announcements of elite soccer players influence the betting odds of affected matches? Analyzing the first four statistical moments of 117,174 odds from 32 bookmakers, we identify initial inertia followed by a lagged reaction that we cannot reason with learning. Our findings raise questions about how bettors and bookmakers incorporate new information into their beliefs. It has broader implications regarding information processing in markets.
How do firms respond to state retirement plan mandates?
Authors: Bloomfield Adam , Lee Kyung Min , Philbrick Jay , Slavov Sita Nataraj
Published: October 2024

We investigate how state “Auto‐IRA” mandates affect firm offerings of employer‐sponsored retirement plans (ESRPs). These policies require firms without ESRPs to facilitate automatic employee contributions to state‐created individual retirement accounts. We find that these policies increase an individual's probability of working for a firm with an ESRP by 6%–9% and of being included in the ESRP by 8%–13%. At the firm level, these policies increase the probability of offering an ESRP by 7%, the probability of establishing a new ESRP by 41%–44%, and the number of ESRP participants by 6 percent.