bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bank relationship and contractual flexibility: Evidence from covenant enforcement
Authors: Gam Yong Kyu , Liu Chunbo 
Published: October 2024

AbstractThis 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

AbstractNeuronal 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

AbstractGenebanks 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

AbstractPyodermatitis 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

ABSTRACTProblemPreterm 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 StudyData 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.ResultsPreterm 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.ConclusionsCMV 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

AbstractAimPaediatricians 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.MethodsA 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.ResultsThe 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.ConclusionUsing 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

AbstractTraditionally, 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

SummaryManagement 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

AbstractOur 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

ABSTRACTDe 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

ABSTRACTGenomic 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

ABSTRACT
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

SummaryTo 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

AbstractConservation 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

AbstractAimAs 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).MethodsPatients 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.ResultsCD31 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).ConclusionMicrovascular 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.