bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and functional validation of an enhancer variant in the 9p21.3 locus associated with glaucoma risk and elevated expression of p16INK4a
Authors: Zhu Yizhou , Tazearslan Cagdas , Rosenfeld Michael G. , Fiser Andras , Suh Yousin 
Published: June 2023

AbstractGlaucoma is a leading cause of irreversible blindness, with advanced age being the single most significant risk factor. However, the mechanisms underlying the relationship between aging and glaucoma remain unclear. Genome‐wide association studies (GWAS) have successfully identified genetic variants strongly associated with increased glaucoma risk. Understanding how these variants function in pathogenesis is crucial for translating genetic associations into molecular mechanisms and, ultimately, clinical applications. The chromosome 9p21.3 locus is among the most replicated glaucoma risk loci discovered by GWAS. Nonetheless, the absence of protein‐coding genes in the locus makes interpreting the disease association challenging, leaving the causal variant and molecular mechanism elusive. In this study, we report the identification of a functional glaucoma risk variant, rs6475604. By employing computational and experimental methods, we demonstrated that rs6475604 resides in a repressive regulatory element. Risk allele of rs6475604 disrupts the binding of YY1, a transcription factor known to repress the expression of a neighboring gene in 9p21.3, p16INK4A, which plays a crucial role in cellular senescence and aging. These findings suggest that the glaucoma disease variant contributes to accelerated senescence, providing a molecular link between glaucoma risk and an essential cellular mechanism for human aging.
Compromisos de rasgos del leño en plantas del desierto: un modelo triangular para comprender las variaciones intra e interespecíficas a lo largo de un gradiente de aridez
Authors: Melián Edgardo , Gatica Gabriel , Pucheta Eduardo 
Published: June 2023

ResumenLa arquitectura hidráulica de las plantas leñosas puede mostrar variaciones intra e interespecíficas a lo largo de gradientes de aridez como resultado de compromisos entre rasgos del leño, que dependen de la capacidad de cada especie para resistir o evadir la sequía. La arquitectura hidráulica de las plantas puede definirse como el conjunto de diferentes tipos celulares implicados en el transporte de agua a través del continuo suelo‐planta‐atmósfera. En la actualidad, existen dos modelos diseñados para comprender los compromisos entre rasgos funcionales leñosos del xilema, desarrollados por Baas y Pratt junto a colaboradores, respectivamente. El primer modelo presenta un espacio triangular de compromisos en el que tres funciones principales del xilema de las plantas están vinculadas entre sí para proporcionar resistencia a la embolia en tiempo evolutivo. El segundo modelo representa los tipos de células del xilema asociados a sus funciones principales, a saber, vasos para transporte, parénquima para almacenamiento y fibras para soporte. Proponemos aquí un nuevo modelo que considera la abundancia individual relativa de rasgos de los tipos de células del xilema para tres especies del desierto con diferentes estrategias de tolerancia a la sequía, a lo largo de un gradiente de aridez de más de 300 mm. De este modo, en nuestro modelo se pueden registrar las variaciones intra e interespecíficas de los rasgos del leño para especies de diferentes localidades a lo largo de un gradiente de aridez. El árbol Neltuma flexuosa mostró poca variación intraespecífica en la parte media de resistencia a la sequía del modelo, lo que sugiere que esta especie es independiente de las precipitaciones. Larrea divaricata también mostró una variación intraespecífica baja, pero su ubicación espacial en el modelo sugiere que tiene una alta tolerancia a la sequía. La tercera especie, Bulnesia retama, mostró la mayor variación intraespecífica dentro del modelo, modificando su arquitectura hidráulica aumentando el área de fibras al incrementar la aridez. Nuestro modelo podría convertirse en una herramienta general para evaluar las variaciones intra e interespecíficas en los compromisos de la arquitectura hidráulica entre plantas leñosas como respuesta a la sequía.
HCM‐associated ALMS1 variant: Allele drop‐out and frequency in Italian Sphynx cats
Authors: Turba Maria Elena , Ferrari Paolo , Milanesi Raffaella , Gentilini Fabio , Longeri Maria 
Published: June 2023

AbstractHypertrophic cardiomyopathy (HCM) is the most common cardiomyopathy in domestic cats, and some inherited variants are available for genetic testing. A variant of the Alstrom syndrome protein 1 gene (ALMS1) was recently reported to be associated with HCM in the Sphynx cat breed (A3: g.92439157G>C). Genetic screening of the variant, promoted by the Osservatorio Veterinario Italiano Cardiopatie and Genefast Laboratory, was offered to Sphynx cat owners and breeders in Italy. Genotype data were initially obtained by Sanger sequencing. In one case where the samples of a trio were available, inconsistency in the vertical transmission of the variant suggested an allele dropout (ADO) of the wt allele. A new external primer pair was designed as an alternative to the original. The larger PCR product obtained was sanger sequenced, and five novel single nucleotide variants (SNVs) not yet annotated in open‐access databases were detected. Three of these SNVs were within the original primer‐binding regions and were assumed to have caused ADO. The haplotype, including the ADO SNVs, was detected in two cats belonging to different lineages. To accurately genotype ALMS1 g.92439157G>C in the samples, we set up a real‐time TaqMan MGB assay while avoiding all surrounding SNVs. At g.92439157G>C, for 136 Sphynx cats, g.92439157 C variant was highly widespread (freq. >0.50). The present study reports five new variants surrounding ALMS1 g.92439157G>C that must be considered when designing the test. The study also indicates the need to verify the correspondence between the g.92439157 C variant frequency and the prevalence of HCM by increasing clinical visits and follow‐ups and finally to promote genetic counselling for accurate management of mating plans in Italian Sphynx cats.
In lieu of “keywords”: Toward an anthropology of rapport
Authors: Carruthers Andrew M. 
Published: June 2023

AbstractThe identification of socioculturally important “keywords” remains a distinctive feature of critical social theory. This article asks why this is so while offering a critique of “keyword projects” as they have been formulated and pursued across cultural studies and anthropology. Such projects often remain inattentive to wider patterns of sign relations, concealing from ethnographic view the very patterns within which key “words” emerge and are embedded. Overlooking these patterns precludes finer‐grained considerations of what makes certain words situationally “key” within sociocultural life. Engaging with migrant mobilities across the borderlands and borderwaters of Indonesia and Malaysia, the article examines keywords not simply as sociocultural formations or semiotic regularities, per se, but as captions for and construals of fashions of speaking and forms of life. Connecting hitherto unconnected accounts of “rapport,” it illustrates how anthropologists might move beyond “keyword talk” to more fully consider how rapport configures anthropological assumptions about “keyness” itself.
Single men's attitudes towards posthumous use of their sperm cryopreserved due to illness in Israel
Authors: Stein Anat , Altman Eran , Rotlevi Mali , Seh Donia , Wertheimer Avital , Ben‐Haroush Avi , Shufaro Yoel 
Published: June 2023

AbstractBackgroundBanking of frozen spermatozoa by single men opens the possibility of procreation long after their death. Requests for posthumous reproduction by the families of the deceased are growing, raising an ethical debate, especially when written instructions were not left by the patients and in cases of unplanned perimortem collection. The issue of the progenitors' intention to procreate after death is the key to ethically based decision‐making in these cases.ObjectivesTo evaluate the attitude of single men cryopreserving spermatozoa before life‐threatening medical situations towards post‐mortem usage of their cryopreserved spermatozoa.Materials & methodsAdult single men prior to sperm cryopreservation before cytotoxic therapy were asked to sign a structured form declaring their will and instructions for the usage of their cryopreserved spermatozoa in case of their demise.ResultsFour hundred fifty‐two men of diverse ethnicity, religious and cultural backgrounds signed the form providing instructions for the use of their cryopreserved spermatozoa in case of mortality. Their age was 27.4 ± 8.06 years. Seven (1.5%) patients willed their spermatozoa for posthumous reproduction to a sibling, 22 (4.9%) to parents, and 26 (5.7%) to their informal female partners. The significant majority (n = 397; 87.8 %) of the single men were ordered to destroy their cryopreserved spermatozoa in case of their expiry. Note that, 26–39 years old men were less likely (81.8% vs. >90% in other ages) to order sperm destruction, as well as men with a poorer prognosis (83% vs. 90%).DiscussionIn this study group, most single men cryopreserving spermatozoa in the face of future life‐threatening morbidity do so for their own future live parenthood, and are not interested in posthumous reproduction.ConclusionOur results doubt the claim that single men who had an unplanned perimortem sperm collection can be universally presumed to have wished to father a child posthumously. Any claimed assumed consent in these cases should be considered for each case individually based on its specific circumstances.
Cesarean section trends from 1992 to 2016 in Estonia and Finland: A registry‐based study
Authors: Sildver Kaire , Veerus Piret , Lang Katrin , Pisarev Heti , Gissler Mika 
Published: June 2023

AbstractIntroductionThe number of cesarean sections (CSs) has grown steadily, but the underlying factors driving this increase remain unknown. Data from Medical Birth Registries were retrieved to analyze CS trends in Estonia and Finland during the period 1992–2016.Material and methodsAll births in Estonia (n = 356 063) and Finland (n = 1 437 234) were included. The differences between Estonia and Finland in five‐year time periods for the total CS rate, and rates in Robson 1, 2, and 5 groups (R1, R2, R5) were analyzed by logistic regression. Total CS rates were adjusted for birthweight, parity, previous CS, gestational age, singleton pregnancy, cephalic position, induction, mother's age. R1; R2; R5 rates were adjusted for birthweight and mother's age.ResultsIn Estonia, the proportion of CSs increased from 6.5% to 21.0% and in Finland from 15.1% to 16.8% between 1992 and 2016. In 2016, Estonia and Finland remained within the target value with their R1 + 2 (Estonia 18%; Finland 16%) and R5 (Estonia 59%; Finland 42%) values.ConclusionsComparing Robson groups in different countries can shed light on divergent CS rates and to improve the quality of perinatal and obstetric care.
Epidemiology and risk factors for histopathologic characteristics of non‐alcoholic fatty liver disease in South America
Authors: Akambase Joseph A. , Prieto Jhon E. , Mattos Angelo Z. , Mattos Angelo A. , Carrera Enrique , Díaz‐Ferrer Javier , Gallardo Patricia , Curia Andrea , Ballerga Esteban G. , Tovo Cristiane V. , Balderramo Domingo , Debes Jose D. 
Published: June 2023

SummaryBackgroundThe burden of non‐alcoholic fatty liver disease (NAFLD) in South America is among the highest in the world. However, the epidemiology and risk factors for NAFLD are insufficiently described in the region.AimTo explore the associations between clinical characteristics and histopathological features of NAFLDMethodsThis was a descriptive study of 2722 patients with NAFLD from 8 medical centres across 5 South American countries. We collected clinical, biochemical and histopathological data using a templated chart. Fibrosis was assessed by elastography or fibrosis scores and confirmed with biopsy when available. We examined associations between histopathological features and clinical characteristics with logistic regression models. Models were adjusted for country, age and sex.ResultsThe median age was 53 years (IQR: 41–62), and 63% were women. Subjects from Brazil had the highest body mass index at 42 kg/m2. Sixty‐seven percent had dyslipidemia, 46% had obesity, 30% had hypertension, 17% had type 2 diabetes mellitus (T2DM) and 34% had metabolic syndrome. Biopsy reports were available for 948 (35%), of which 58% showed fibrosis, 91% steatosis and 65% inflammation; 25% showed significant fibrosis and 27% severe steatosis. Metabolic syndrome, T2DM and hypertension were significantly associated with significant fibrosis (OR = 1.94, p < 0.001; OR = 2.93, p < 0.001 and OR = 1.60, p = 0.003, respectively), severe steatosis (OR = 2.05, p < 0.001; OR = 1.91, p = 0.001 and OR = 2.17, p < 0.001, respectively) and liver inflammation (OR = 1.66, p = 0.007; OR = 2.00, p = 0.002; OR = 1.62, p = 0.001, respectively).ConclusionsIn the largest NAFLD cohort study to date from South America, metabolic syndrome, hypertension and T2DM were independently associated with significant fibrosis, severe steatosis, and inflammation. The prevalence of T2DM was lower than the reported global prevalence.
Combined thoraco‐laparoscopic hepatectomy concomitant with resection of the diaphragm for solitary peritoneal seeding from cervical cancer: A case report
Authors: Matsumura Masaru , Seyama Yasuji , Ogawa Rei , Nemoto Satoshi , Tani Keigo , Kawata Yoshiko , Yasugi Toshiharu , Horio Hirotoshi 
Published: June 2023

AbstractCombined thoraco‐laparoscopic resection can aid in precise resection of an invasive tumor of the diaphragm. A 44‐year‐old woman was referred to our department for resection of solitary peritoneal seeding from cervical cancer following systemic chemotherapy. The tumor was located in the right diaphragm with an ill‐defined border of the liver. Combined thoraco‐laparoscopic resection was proposed. Laparoscopy portrayed that the right diaphragm was partially attached to the liver, and the depth of tumor invasion to the diaphragm was ambiguous. Observation from the thoracic cavity indicated a white‐colored distortion following the location of peritoneal seeding. Partial resection and repair of the diaphragm were made using the thoracoscopic‐assisted approach, followed by laparoscopic hepatectomy. The postoperative course was uneventful, and pathological findings revealed that peritoneal metastases of the diaphragm and surgical margin was negative for cancer. Combined thoraco‐laparoscopic resection can cover the drawbacks of each approach and is among the options for minimally invasive surgery for invasive tumor of the diaphragm.
Adverse effects of an aldosterone synthase (CYP11B2) inhibitor, fadrozole (FAD286), on inflamed rat colon
Authors: Launonen Hanna , Toivio Lotta , Linden Jere , Siltari Aino , Salmenkari Hanne , Korpela Riitta , Vapaatalo Heikki 
Published: June 2023

AbstractRecently, we described local aldosterone production in the murine large intestine. Upregulated local aldosterone synthesis in different tissues has been linked with inflammatory conditions, which have been attenuated by the aldosterone synthase (CYP11B2) inhibitor, fadrozole (FAD286). Therefore, we investigated the effect of inhibition of intestinal aldosterone synthesis on the development of intestinal inflammation. Sprague‐Dawley rats were administered 5% (v/w) dextran sodium sulphate (DSS) for 7 days with or without daily FAD286 (30 mg/kg/d) subcutaneous injections on 3 days before, during and one day after DSS. Tissue aldosterone concentrations were evaluated by ELISA, CYP11B2 by Western blot and RT‐qPCR. FAD286 halved adrenal aldosterone production but, intriguingly, increased the colonic aldosterone concentration. The lack of inhibitory effect of FAD286 in the colon might have been affected by the smaller size of colonic vs. adrenal CYP11B2, as seen in Western blot. When combined with DSS, FAD286 aggravated the macroscopic and histological signs of intestinal inflammation, lowered the animals' body weight gain and increased the incidence of gastrointestinal bleeding and the permeability to iohexol in comparison to DSS‐animals. To conclude, FAD286 exerted harmful effects during intestinal inflammation. Local intestinal aldosterone did not seem to play any role in the inflammatory pathogenesis occurring in the intestine.
Knowledge, attitudes, and practices toward COVID‐19 among pregnant women in Jordan during the COVID‐19 outbreak
Authors: Mrayan Lina , Abujilban Sanaa , Tanash Muath , Obeisat Salwa 
Published: June 2023

AbstractBackgroundCOVID‐19 is highly infectious and can cause harmful effects in pregnant women. As COVID‐19 is a relatively new disease, there is a continuing need to assess the knowledge, attitudes, and practices (KAP) toward this virus among pregnant women globally in order to identify any gaps and suggest ways to address them. Little is known about how pregnant Jordanian women responded to the pandemic.ObjectiveThe purpose of this study was to investigate the level of KAP toward COVID‐19 among pregnant women in Jordan and to detect the variables associated with a satisfactory KAP level.MethodsA cross‐sectional online survey based on a predesigned KAP survey was modified for use among pregnant women in Jordan. The data obtained from 574 participants were analyzed using the Statistical Package for the Social Sciences, version 23.ResultsOverall, pregnant women in Jordan were found to be knowledgeable, to have a positive attitude, and to exhibit good practices in relation to COVID‐19. Some demographic factors were significantly associated with high levels of knowledge, positive attitudes, and safer practices.ConclusionsResults suggest that special attention should be given by the government to pregnant women with respect to any future emergent situations such as additional COVID‐19 surges or other novel respiratory conditions in order to ensure that they are fully informed and prepared.
pH‐dependent modulation of TRPV1 by modality‐selective antagonists
Authors: Daniluk Jan , Voets Thomas 
Published: June 2023

AbstractBackground and PurposeAntagonists of TRPV1 that inhibit all activation modes cause hyperthermia, hampering their medical use as novel analgesics. TRPV1 antagonists that do not (fully) inhibit responses to low pH do not cause hyperthermia, but it remains incompletely understood how such antagonists affect channel gating. We tested the hypothesis that pH‐sparing antagonists act in a modality‐selective manner on TRPV1, differentially affecting channel activation by protons and capsaicin.Experimental ApproachUsing whole‐cell patch‐clamp and calcium imaging to measure channel activity in cells expressing wild type human TRPV1 or the pH‐insensitive mutant F660A. Responses to protons and capsaicin were measured at different pH values in the presence of antagonists that reportedly partially spare (A‐1165442) or potentiate (AMG7905) acid‐evoked channel activation.Key ResultsAt pH 5.5, A‐1165442 was equipotent at blocking acid‐ and capsaicin‐evoked responses of wild type TRPV1. Its potency to inhibit acid‐evoked responses was attenuated at pH ≤ 5.0. AMG7905, at a concentration (1 μM) that fully inhibits capsaicin‐evoked responses, potentiated proton‐evoked (pH 5.5) responses of wild type TRPV1. In the F660A mutant, the inhibitory efficacy of A‐1165442 and AMG7905 towards capsaicin‐evoked responses was reduced at lower pH values and AMG7905 acted as a partial agonist.Conclusion and ImplicationsOur findings show that A‐1165442 and AMG7905 interact in a pH‐dependent manner with TRPV1, but this pH dependence is not strictly modality‐selective. Reduced TRPV1 antagonism at acidic pH may limit analgesic efficacy in injured tissue and needs to be considered in models explaining the effects of antagonists on core body temperature.
Exploring self‐care practices of African American informal kinship caregivers
Authors: Washington Tyreasa , Walton Quenette L. , Kaye Hannah , Hong Jun Sung , Cook Benjamin 
Published: June 2023

AbstractAfrican American caregivers providing informal kinship care are vulnerable to chronic stress. Research has indicated stress increases individuals' risk for many adverse physical and mental health outcomes, including cardiovascular disease, Alzheimer's disease and depression. Given the adverse outcomes related to stress, identifying mechanisms to help these caregivers lower and manage their stress is critical to their overall health and well‐being. This pilot qualitative study aimed to explore the self‐care practices of 12 African Americans providing informal kinship care using a phenomenological approach. Three themes emerged: (a) behaviours to manage stress levels, (b) support network reminding caregivers to take care of themselves and (c) prioritizing my own needs. Specifically, our findings indicate that some caregivers have high‐stress levels and engage in maladaptive coping behaviours. The children they cared for reminded them to take care of themselves by attending doctors' appointments or getting their nails done. Nevertheless, some caregivers prioritized their needs by participating in positive self‐care behaviours, such as listening to jazz and gospel music and exercising. Prevention and intervention programs that focus on improving caregivers' health should consider the role of self‐care practices.
Recommendations for risk minimization when using Janus kinase inhibitors for the treatment of chronic inflammatory skin diseases
Authors: Wohlrab Johannes , Kegel Thomas , Große Regina , Eichner Adina 
Published: June 2023

SummaryIn accordance with article 20 of Regulation (EC) No 726/2004, the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) has re‐evaluated the safety of Janus kinase inhibitors for the treatment of inflammatory diseases and formulated safety information deviating from the previous indications in the respective summary of product characteristics of the products concerned. These refer to the consideration of a possibly increased risk of venous thromboembolic or severe cardiovascular events, an increased infection rate and an increase in the prevalence of skin cancer across drugs and indications. Therefore, in patients with independent risk factors (age 65 years and older, smokers or former smokers, patients with oral contraception or hormone replacement therapy and other risk factors), it is recommended to use Janus kinase inhibitors therapeutically only if there are no suitable treatment alternatives. To facilitate a pragmatic and thorough detection of high‐risk patients in everyday clinical practice, an interdisciplinary checklist was developed that is suitable as a working tool from the perspective of the dermatologist.
Indoor air pollution and child development in Indonesia: Stunted by the smoke?
Authors: Kim Younoh , Manley James , Radoias Vlad 
Published: June 2023

AbstractMotivationAir pollution in general, and indoor air pollution in particular, have been linked to severe, acute ill health. Less attention has been paid to long‐term outcomes such as stunting (height for age).PurposeDoes reduced air pollution inside the home resulting from burning cleaner fuels affect child development?Methods and approachWe compare stunting of persons aged under 20 years of age in households with and without clean stoves between 1997 and 2000. Data come from the Indonesian Family Life Survey, a repeat survey that includes over 30,000 respondents. We model relations by regression; correcting for endogeneity (wealth affects both health and choice of stove) and confounders by using instrumental variables.FindingsUsing a clean stove leads to a 0.28 standard deviation reduction in stunting. The result is significant and consistent across specifications; the estimate is double the size of estimates that do not address the endogeneity of wealth.Policy implicationsPolicy‐makers should encourage households to adopt clean stoves and to use clean fuels. Public intervention is especially indicated in rural areas, where many households prefer to use cheaper, but polluting, stoves and fuels.