bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whole genome sequencing identifies rare genetic variants in familial pancreatic cancer patients
Authors: Tan Ming , Brusgaard Klaus , Gerdes Anne‐Marie , Larsen Martin Jakob , Mortensen Michael Bau , Detlefsen Sönke , de Muckadell Ove B. Schaffalitzky , Joergensen Maiken Thyregod 
Published: March 2022

AbstractPancreatic ductal adenocarcinoma (PDAC) represents one of the most lethal malignancies with very high mortality and short survival time. About 5–10% of the PDAC patients have a familial predisposition to the disease designated as familial pancreatic cancer (FPC), suggesting genetic modulation of FPC pathogenesis. It is estimated that currently identified sequence variants account for less than 20% of the genetic basis of FPC leaving the majority of the genetic architecture unclarified. We performed whole genome sequencing (WGS) analysis on benign formalin‐fixed paraffin‐embedded (FFPE) tissues from 35 FPC patients focusing on genes enriched by rare and functional sequence variants. We identified 40 genes hosting at least 2 protein truncating variants (PTVs). Significant overlaps of the 40 genes were found (p < 1 × 10–22) with cancer genes, cancer driver genes and genes found in previous studies on cancer, including ATM, POLE, BRCA2, TYR03, PABPC1 and SSC5D. The PTV genes are significantly overrepresented in biological pathways in cancer development and progression including extracellular matrix organization, signaling by RHO GTPases and RHO GTPase cycle. Association analysis using external controls detected 6 genes with p < 0.05. The WGS analysis revealed high heterogeneity in the detected rare variants among FPC patients and provides novel genes harboring potential mutational hotspots for future validation and replication.
A retrospective study of the behavioural and psychological symptoms of dementia in patients admitted to a Specialist Dementia Care Unit
Authors: Djekovic Kate , Clowes Kim , Spalding Natasha , Waite Louise 
Published: March 2022

AbstractObjectivesTo explore the nature and severity of behavioural and psychological symptoms of dementia (BPSD) and outcomes for patients admitted to a specialist dementia care unit (SDCU) at a tertiary Australian hospital.MethodsThis single‐centre retrospective study categorised patients into a recognised seven‐tiered model of severity of BPSD using a novel tool developed for this study. Descriptive characteristics, pharmacological management, and range and severity of BPSD were examined.ResultsThere were 125 patients admitted over a two‐year period reviewed, with 62% being males and a mean age of 82.4 years. Those with high severity BPSD (n = 61, 49%) had a longer length of stay (p = 0.049), were on a greater number of psychotropic medications on admission (p < 0.001) and were more likely to be trialled on a new psychotropic medication (p = 0.001). At least five behaviours on admission were demonstrated in 84% of patients. Behaviours were ameliorated with reduction in tier severity at discharge (p < 0.005). The mean number of psychotropic medications on admission was not significantly different to discharge (p = 0.14). Sixty‐seven per cent of patients living independently at admission were discharged to residential care, and 44% in residential care were discharged to a new facility.ConclusionsMulti‐disciplinary management led to optimisation of behaviours and overall reduction in BPSD severity. This was achieved without a significant increase in the use of psychotropic medications, highlighting the importance of an individualised approach by a team skilled in the behavioural management of BPSD. The study confirms the high risk of transition to residential care for patients with BPSD.
Review article: paradoxical psoriasis as a consequence of tumour necrosis factor antagonists in patients with inflammatory bowel disease
Authors: Townsend Cassandra Marie , Lovegrove Fiona , Khanna Reena , Wilson Aze Suzanne 
Published: March 2022

SummaryBackgroundTumour necrosis factor (TNF) antagonists are an efficacious therapy used in the management of several immune‐mediated inflammatory diseases, including inflammatory bowel disease (IBD) and psoriasis. However, since being prescribed more widely, reports of new‐onset psoriatic lesions have began to emerge in the literature and are known as paradoxical psoriasis.AimTo review the evidence available in both the dermatology and gastroenterology literature pertaining to the entity known as paradoxical psoriasis as it relates to IBD and to create a comprehensive guide to assist clinicians who treat this challenging patient population.MethodsA literature search was conducted in PubMed to identify manuscripts that presented, discussed or summarised data pertaining to paradoxical psoriasis presenting in individuals with IBD.ResultsParadoxical psoriasis is now thought to be a contradictory effect of TNF antagonist therapy leading to psoriatic lesions often within the first year of treatment. The underlying pathogenesis, although not completely understood, is likely related to an imbalance of inflammatory cytokines. The histological appearance, while similar to classical psoriasis, does have unique features. The clinical presentation can vary among patients but often presents during maintenance therapy for inflammatory bowel disease. Treatment options should be determined based upon the severity of the skin lesion, activity of the underlying inflammatory bowel disease and the patient’s unique clinical history.ConclusionsThe approach to paradoxical psoriasis in IBD should be discussed with a multidisciplinary team to optimise and preserve intestinal disease remission and to ensure the resolution of debilitating skin lesions.
Laparoendoscopic single‐site surgery for urachal remnant with extraperitoneal approach through a suprapubic port
Authors: Hoshi Akio , Chihara Ichiro , Shiga Masanobu , Nitta Satoshi , Nagumo Yoshiyuki , Sakka Shotaro , Kojo Kosuke , Ikeda Atsushi , Yoshino Takayuki , Kimura Tomokazu , Kawahara Takashi , Kandori Shuya , Negoro Hiromitsu , Nishiyama Hiroyuki 
Published: March 2022

AbstractIntroductionNo standard procedure has been established for laparoendoscopic single‐site surgery for urachal remnants (LESS‐U). This study aimed to report the novel surgical techniques and initial outcomes of laparoendoscopic single‐site surgery with an extraperitoneal approach through a suprapubic port for urachal remnants (spLESS).MethodsFifty‐five patients (median age, 27 years; range, 15–69 years) who underwent LESS‐U were analyzed. To overcome the limitations inherent in the conventional procedure (LESS‐U through an umbilical port: uLESS), we modified the port placement and approached via the extraperitoneal space. spLESS is a novel procedure which reduces intestinal damage caused by the extraperitoneal approach and overcomes incomplete resection of the urachal remnant, especially in the bladder dome. Three trocars are inserted into the extraperitoneal space through a suprapubic port in spLESS, and complete resection of the urachal remnant from the umbilicus to the bladder is performed with an appropriate incision line. Patient characteristics and perioperative results were retrospectively collected. Cosmetic outcomes were prospectively evaluated using self‐administered questionnaires (body image and photo‐series questionnaire).ResultsspLESS and uLESS were performed in 43 and 12 patients, respectively. No differences were observed between the perioperative results. The cosmetic outcomes were compared between the groups using body image and photo‐series questionnaires. No patient developed major complications; there was no recurrence in either group.ConclusionsspLESS is a novel procedure which can completely resect the urachal remnant and reduce the risk of intestinal damage. spLESS is a safe, effective, and feasible procedure with high postoperative cosmesis.
Ground‐penetrating radar (GPR) investigations of a large‐scale buried ice‐marginal landsystem, Skeiðarársandur, SE Iceland
Authors: Harrison Devin , Ross Neil , Russell Andrew J. , Jones Stuart J. 
Published: March 2022

The sedimentary record of Icelandic ice‐contact environments provides critical insights into past glacier margin dynamics and position, relative sea level, and the geomorphic processes that drive the evolution of proglacial environments. This important archive has been little exploited, however, with most glacier and sea‐level reconstructions based on limited sedimentary exposures, coring and surface geomorphic evidence. We report an extensive (42 km of data within a 24‐km2 study area) and deep (reflections recorded at depths up to 100 m) low‐frequency (40 and 100 MHz) ground‐penetrating radar (GPR) survey of the Sandgígur moraines, SE Iceland. GPR profiles reveal a much larger (67 m high) and extensive (1.25 km wide) buried moraine ridge than that suggested by surface topography (typically 125 m wide and 7 m high). These data reveal that the Sandgígur moraines was deposited during a major Holocene re‐advance of Skeiðarárjökull. The moraine ridge is buried by sediments dominated by glacifluvial deposits with an estimated sediment volume of 1.04 km3. We combine GPR‐derived subsurface architecture and the surface morphology to develop a conceptual model detailing the geomorphic evolution of the moraine and surrounding region. These results provide new insights into the Holocene evolution of Skeiðarársandur, identifying the presence of a former major ice‐margin position, as well as a past relative sea‐level limit. Furthermore, we establish that sediment supply and available terrestrial accommodation space are dominant drivers in the formation and evolution of vast sandar environments.
Hurricane‐associated population decrease in a critically endangered long‐lived reptile
Authors: van den Burg Matthijs P. , Madden Hannah , van Wagensveld Timothy P. , Boman Erik 
Published: March 2022

AbstractCatastrophic events, like hurricanes, bring lethal conditions that can have population‐altering effects. The threatened Caribbean dry forest occurs in a region known for its high‐intensity hurricane seasons and high species endemism, highlighting the need to better understand hurricane impacts in combination with habitat fragmentation and loss. However, such studies remain rare and for reptiles are mostly restricted to Anolis. Here, we used single‐season occupancy modeling to infer the impact of the intense 2017 Atlantic hurricane season on the critically endangered Lesser Antillean Iguana, Iguana delicatissima. We surveyed 30 transects across eight habitats on St. Eustatius during 2017–2019, which resulted in 344 individual surveys and 98 iguana observations. Analyses of abundance and site occupancy indicated both measures for 2018 and 2019 were strongly reduced compared to the pre‐hurricane 2017 state. Iguanas at higher elevations were affected more profoundly, likely due to higher wind speeds, tree damage, and extensive defoliation. Overall, our results indicate a decrease in population estimates (23.3%–26.5%) and abundance (22%–23.8%) for 2018 and 2019, and a 75% reduction in opportunistic sightings of tagged iguanas between 2017 and 2018. As only small and isolated I. delicatissima populations remain, our study further demonstrates their vulnerability to stochastic events. Considering the frequency and intensity of hurricanes are projected to increase, our results stress the urgent need for population‐increasing conservation actions in order to secure the long‐term survival of I. delicatissima throughout its range. Given the projected increase and poleward shift of hurricanes, our study provides important insights from a non‐model species.
In silico design of a novel nucleotide antiviral agent by free energy perturbation
Authors: Patel Dharmeshkumar , Cox Bryan D. , Kasthuri Mahesh , Mengshetti Seema , Bassit Leda , Verma Kiran , Ollinger‐Russell Olivia , Amblard Franck , Schinazi Raymond F. 
Published: March 2022

AbstractNucleoside analogs are the backbone of antiviral therapies. Drugs from this class undergo processing by host or viral kinases to form the active nucleoside triphosphate species that selectively inhibits the viral polymerase. It is the central hypothesis that the nucleoside triphosphate analog must be a favorable substrate for the viral polymerase and the nucleoside precursor must be a satisfactory substrate for the host kinases to inhibit viral replication. Herein, free energy perturbation (FEP) was used to predict substrate affinity for both host and viral enzymes. Several uridine 5’‐monophosphate prodrug analogs known to inhibit hepatitis C virus (HCV) were utilized in this study to validate the use of FEP. Binding free energies to the host monophosphate kinase and viral RNA‐dependent RNA polymerase (RdRp) were calculated for methyl‐substituted uridine analogs. The 2’‐C‐methyl‐uridine and 4’‐C‐methyl‐uridine scaffolds delivered favorable substrate binding to the host kinase and HCV RdRp that were consistent with results from cellular antiviral activity in support of our new approach. In a prospective evaluation, FEP results suggest that 2’‐C‐dimethyl‐uridine scaffold delivered favorable monophosphate and triphosphate substrates for both host kinase and HCV RdRp, respectively. Novel 2’‐C‐dimethyl‐uridine monophosphate prodrug was synthesized and exhibited sub‐micromolar inhibition of HCV replication. Using this novel approach, we demonstrated for the first time that nucleoside analogs can be rationally designed that meet the multi‐target requirements for antiviral activity.
Parent's self‐reported tooth brushing and use of fluoridated toothpaste: Associations with their one‐year‐old child's preventive oral health behaviour
Authors: Suokko Hanna , Tolvanen Mimmi , Virtanen Jorma , Suominen Auli , Karlsson Linnea , Karlsson Hasse , Lahti Satu 
Published: March 2022

AbstractObjectiveThe aim of the study was to examine if the tooth brushing frequency and use of fluoridated toothpaste of the mother and father were associated with the tooth brushing frequency and use of fluoridated toothpaste for their 1‐year‐old child.MethodsThis cross‐sectional study is part of the FinnBrain Birth Cohort Study. Questionnaire data were obtained from 1672 mothers and 867 fathers on tooth brushing and use of fluoridated toothpaste, age, education, number of siblings and parity (when the child was 1‐year‐old). For 763 families (mother and father), data from both parents were available. Tooth brushing was dichotomized to at least twice daily (2× day) and less than 2× day, and use of fluoridated toothpaste for child to at least once daily and less than once daily. The association between brushing of child's teeth (both parents less than 2× day) and use of fluoridated toothpaste for the child (both parents less than once daily) with parent's own tooth brushing was modelled with logistic regression analyses adjusted for family‐related variables (parents' age and education, number of older siblings) using odds ratios (OR) and 95% confidence intervals (CI).ResultsFamilies in which both parents brushed their own teeth less than 2× day were more likely to brush their child's teeth less than 2× day than families in which both parents brushed their own teeth 2× day (OR = 9.23; 95%CI = 5.42–15.69). The likelihood of not brushing the child's teeth 2× day was less strong when at least one of the parents brushed his/her own teeth 2× day (mother 2× day: OR = 1.97; 95%CI = 1.25–3.10; father 2× day: OR = 2.85; 95%CI = 1.51–5.40).ConclusionsLess frequent tooth brushing of both mothers and fathers was strongly associated with less frequent tooth brushing of their child. When educating parents on child oral home care, parents' own home care and inclusion of fathers also need more attention.
I have to hold it together: Trauma in law enforcement couples
Authors: Campbell Avery R. , Landers Ashley L. , Jackson Jeffrey B. 
Published: March 2022

AbstractObjectiveGrounded in secondary traumatic stress theory, this study explored the impact of work‐related traumatic stress on law enforcement couples.BackgroundStudies exploring the impact of traumatic stress on law enforcement couples are limited. Such studies suggest that when traumatic stress impacts law enforcement professionals, their spouses often experience secondary traumatic stress and serve in a supportive role after trauma exposure.MethodSemistructured dyadic interviews were conducted with law enforcement couples (N = seven couples, 14 participants) using transcendental phenomenology.ResultsThree themes emerged within the data that captured the essence of law enforcement couples' experiences of traumatic stress: (a) the stressful nature of the law enforcement profession, (b) the impact of work‐related traumatic stress on the couple relationship, and (c) protective factors and resilient coping characteristics.ConclusionThe impact of work‐related traumatic stress manifested in couple's communication, role responsibilities and parenting, and commitment to the relationship and the profession. The impact of work‐related traumatic events differed for the law enforcement professional and their spouse based on the type of traumatic event. Overall, work‐related traumatic stress led couples to engage in a meaning‐making process and activation of resilient couple coping characteristics.ImplicationsGiven the significant impact that work‐related traumatic stress has on the law enforcement couple dyad, couple and family therapy services are needed for law enforcement professionals and their spouses. Couple and family therapists, family researchers, and other professionals working to promote healthy couple and family relationships should inquire about how couples adapt to traumatic stress and reinforce use of resilient coping characteristics.
Numerical Modeling of Head Losses in Different Types of Well Screens
Authors: Bayer‐Raich Martí , Jordana Salvador , Jaime Oscar M. , Lynch Timothy D. , McGillicuddy Kevin B. , Guimerà Jordi , Jaime M. Javier 
Published: March 2022

AbstractQuantifying total well loss through well screens has been traditionally undertaken through experimentally based empirical equations or equations derived for water flow through (circular) orifices. Advances in computer capacity enables incorporation of CFD formulations at millimeter scale, coupling Darcy flow and Reynolds Averaged Navier Stokes (RANS) to better understand and quantify processes related to well loss for different screen types. This study provides a methodology of quantifying well screen head loss using numerical models, coupling Darcy flow (aquifer and filter/gravel pack) with turbulent flow (in‐well and through screen) at a sub‐millimeter scale. Results are used to compare performance of four different types of well screens (Louver, slotted, bridge and wire wrap) and their overall impact and contribution to total well head loss for different slot apertures, pumping rates and hydraulic conductivity of the filter/gravel pack providing a new empirical formulation to quantify screen head loss.
Antiretroviral drug switches to zidovudine‐based regimens and loss to follow‐up during the first COVID‐19 lockdown in Bali, Indonesia
Authors: Gedela Keerti , Rajus Ngurah , Luis Hendry , Fridayantara Wayan Dede , Irwanto Irwanto , Sukmaningrum Evi , Wignall Frank Stephen 
Published: March 2022

AbstractObjectivesInternational lockdowns during the COVID‐19 pandemic impacted antiretroviral drug supplies in Indonesia. We assessed the impact of antiretroviral treatment (ART) provision and being lost to follow‐up (LTFU) on people living with HIV, attending a key population‐focused HIV clinic in Denpasar, Bali.MethodsThis was a retrospective note review of anonymized data from adult Indonesian patients living with HIV. We collected demographic data and information on being LTFU, and assessed the numbers of patients impacted by ART switches from fixed‐dose combination (FDC) tenofovir/lamivudine/efavirenz to multi‐pill zidovudine‐based regimens, during the first international lockdown from March 2020.ResultsRecords of 260 Indonesian adult patients registered for HIV care and prescribed ART were reviewed; 240 (92.3%) were men, and 90% were men who have sex with men. Between 13 March and 28 May 2020, 214 (87%) out of 247 patients (previously diagnosed with HIV) had to switch to individual, multi‐pill zidovudine‐based regimens from their FDC. The switch lasted a mean of 35 days (range 10–85). Twenty‐five patients (10%) were LTFU; patients who switched were more likely to remain in care. Data on viral load status and toxicity are lacking as laboratory testing requires self‐payment.ConclusionsThe majority of patients living with HIV had no choice but to switch to multi‐pill, zidovudine‐based regimens.Despite significant efforts to minimize the impact of lockdown on care, 10% of patients were LTFU. Patients switching ART required greater clinic attention and support, improving retention.Complete national data are needed to understand the impact of ART stockouts on virological suppression and drug resistance throughout Indonesia.
Soybean extruded by‐products as substrate for obtaining food ingredients containing probiotics
Authors: Castellanos‐Fuentes Adriana P. , Cortés Nazareno , Genevois Carolina E. , Flores Silvia K. , de Escalada Pla Marina F. 
Published: March 2022

SummaryExtruded expeller meal (EEM) was widely used for feed production, but few exploited it as a food ingredient. Solid‐state fermentation (SSF) was applied for obtaining food ingredients (FI) based on EEM containing Lacticaseibacillus casei. The FI were characterised physicochemically and functionally. The effect of the SSF on these characteristics as well as the effect of the expeller matrix on the survival capacity of L. casei in in vitro gastrointestinal digestion and on epithelial adhesion were analysed. In general, the SSF process did not produce significant changes on the nutritional and functional properties studied. Probiotic cells supported in the FI were stable for 42 days showing >106 log (CFU g−1) viable probiotic microorganisms. More than 60% of them survived to gastrointestinal simulated conditions. Expeller matrix interfered the adhesion of L. casei with the epithelium. The FI could be incorporated to a porridge for improving the nutritional profile and providing functionality.
Rapidly progressive crescentic diabetic nephropathy: two case reports
Authors: Schroers Jade E. , Gilbert Alexander M. , McKenzie Paul R. , Kirwan Paul D. , Chadban Steven J. , Ying Tracey 
Published: March 2022

AbstractCrescents are not a well recognised feature of diabetic nephropathy. We present two cases of patients presenting with a rapid decline in renal function and subacute onset of nephrotic syndrome. Glomerulonephritis screening was negative, and renal biopsy revealed non‐necrotising cellular crescents and typical features of late‐stage diabetic nephropathy. We review the literature for diabetic nephropathy with crescents and explore possible underlying mechanisms.
Real‐world experience with limited screening for occult malignancy in patients presenting with spontaneous venous thromboembolism: a single‐centre, retrospective cohort study
Authors: Grainger Brian T. , McCrea Te Apatuoterangi , Eaddy Nicola , Ockelford Paul , Young Laura 
Published: March 2022

AbstractSpontaneous venous thromboembolism (VTE) may represent the first manifestation of previously undiagnosed malignancy; however, contemporary international guidelines call for a limited approach to screening for malignancy in such patients. This retrospective cohort study of 328 patients presenting to the Auckland City Hospital Thrombosis Unit identified 17 patients who were subsequently diagnosed with some form of malignancy within 12 months of their presentation. Review of their history, physical examination and limited age and gender‐appropriate cancer screening investigations as described by the National Institute for Clinical Excellence and International Society of Thrombosis and Haemostasis guidelines revealed that all 17 would have been safely diagnosed by the ‘limited’ screening approach endorsed by these guidelines, thus presenting a ‘real‐world’ basis for clinicians to pursue ‘limited’ screening for malignancy in their everyday practice in patients with spontaneous VTE.