bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase I, open‐label, single‐dose study to evaluate the effect of hepatic impairment on the pharmacokinetics and safety of futibatinib
Authors: Gao Ling , Yamamiya Ikuo , Pinti Mark , Rondon Juan Carlos , Marbury Thomas , Tomlinson Gareth , Makris Lukas , Hangai Nanae , Wacheck Volker 
Published: August 2023

AbstractFutibatinib is a covalently binding FGFR1–4 inhibitor that received US Food and Drug Administration approval for the treatment of patients with previously treated, advanced intrahepatic cholangiocarcinoma harboring FGFR2 gene fusions/rearrangements. This phase I trial evaluated the pharmacokinetics (PKs), safety, and tolerability of futibatinib in subjects with impaired hepatic function and matched healthy volunteers. Twenty‐two subjects with hepatic impairment (8 mild [Child‐Pugh 5–6], 8 moderate [7–9], and 6 severe [10–15]) and 16 matched healthy control subjects received a single oral dose of futibatinib 20 mg. Futibatinib PKs were compared between subjects with mild/moderate/severe hepatic impairment and each corresponding control cohort and the overall control cohort. Relationships between futibatinib PKs and Child‐Pugh scores and liver function tests were examined via scatter/regression plots. Compared with matched controls, the area under the plasma concentration–time curve from time zero to infinity increased by 21%/20%/18% and the maximum plasma concentration (Cmax) increased by 43%/15%/10% in subjects with mild/moderate/severe hepatic impairment, respectively. Changes were not considered clinically relevant: geometric mean ratios were within 80%–125%, except for Cmax in subjects with mild hepatic impairment (143%). No obvious trends were observed among futibatinib PK parameters versus Child‐Pugh scores, bilirubin, albumin, international normalized ratio, and aspartate aminotransferase (all p > 0.05). Futibatinib was well‐tolerated, with only four grade 1 treatment‐emergent adverse events (mild hepatic impairment = 2 and control = 2). The results demonstrate that futibatinib dose adjustments due to mild/moderate/severe hepatic impairment are not necessary in patients receiving futibatinib 20 mg daily.
One Thing Leads to Another: Supporting DE&I and Mental Health Through Multisensory Workplace Design
Authors: Marsh Melissa 
Published: August 2023

While the importance of mental health in the workplace is gaining attention, so is the impact that the physical workplace itself has on employee well‐being.Explore the many intricacies of reimagining the workplace to prioritize worker mental health and well‐being—priorities that will ultimately improve employee morale and retention.
Fostering an Environment of Belongingness in the Post‐pandemic Workplace
Authors: Aftab Mersha , Pinnock Hannah 
Published: August 2023

Post‐pandemic work is different, and many organizations have embraced this new way of working with little time to consider the policy, strategy, or impact on people.Remote and hybrid work have changed and challenged how we interact with each other in our jobs, elevating the importance of fostering belongingness in the workplace.
Comparative evaluation of the sedative and physiological effects of dexmedetomidine alone and in combination with methadone, morphine, tramadol or pethidine in miniature donkeys
Authors: Samimi Amir Saeed , Molaei Mohammad Mahdi , Safizadeh Zahra , Allahtavakkoli Mohammad 
Published: August 2023

SummaryBackgroundThe use of combinations of α2‐adrenergic agonists and opioids has been published as providing superior sedation than either drug alone.ObjectivesThe present study aimed to compare the sedative and physiological effects of intravenous (IV) administration of dexmedetomidine alone and in combination with methadone, morphine, tramadol or pethidine in miniature donkeys.Study designExperimental, crossover Latin square, randomised, blinded study.MethodsTwelve clinically healthy miniature donkeys with a mean age of 6 ± 2 (mean ± SD) years, weight of 94 ± 5 kg and height at withers of 0.80 ± 0.06 m were assigned to six IV treatments. They received either 0.9% saline, 5 μg/kg dexmedetomidine, 5 μg/kg dexmedetomidine and 0.2 mg/kg methadone, 5 μg/kg dexmedetomidine and 0.1 mg/kg morphine, 5 μg/kg dexmedetomidine and 2 mg/kg tramadol or 5 μg/kg dexmedetomidine and 1 mg/kg pethidine, with a washout period of 8 days. The degree of sedation was investigated using a numerical ranking scale of 0–3. Heart rate (HR), respiratory rate (RR), rectal temperature (RT) and intestinal motility were performed before and 5, 10, 15, 30, 45, 60, 75, 90 and 120 min after drug administration.ResultsAnimals in dexmedetomidine or dexmedetomidine/opioid treatments were sedated for 5–60 min. Sedation was significantly higher in dexmedetomidine/opioid treatments than in dexmedetomidine at 15–30 min (p < 0.05). In all treatments, HR and RR significantly decreased from baseline at 5–75 and 30–60 min, respectively (p < 0.05). Intestinal motility was decreased in dexmedetomidine and dexmedetomidine/opioid treatments at 5–60 and 5–90 min, respectively. Compared to dexmedetomidine, intestinal motility was significantly lower in dexmedetomidine/opioid treatments at 75–90 min.Main limitationsAssessment of only HR and RR are inadequate to describe the cardiorespiratory effects of dexmedetomidine/opioids.ConclusionsThe use of combinations of dexmedetomidine/opioids would be considered for superior sedation for 15–30 min after administration in miniature donkeys. No significant differences were detected between opioids in combination with dexmedetomidine in miniature donkeys.
Functional non‐equivalence in ecosystem engineers? Different freshwater mussels (Bivalvia: Unionidae) are associated with different macroinvertebrate communities in a subtropical lake
Authors: Ollard Isobel , Chowdhury Gawsia W. , Aldridge David C. 
Published: August 2023

Abstract

Freshwater mussels (Bivalvia: Unionidae) are often described as ecosystem engineers, with the capacity to alter abiotic habitats; this can facilitate certain macroinvertebrate taxa, increasing biodiversity and potentially altering community composition. Mussel species are often implicitly considered to be broad ecological equivalents, with similar impacts on abiotic environments and benthic communities. This assumption of redundancy is important in conservation approaches that aim to preserve ecosystem functioning, rather than species identity. We tested this assumption of equivalence in two species of subtropical freshwater mussels, Lamellidens marginalis and Parreysia caerulea, studying the associations between these mussel species and macroinvertebrate communities.

We measured mussel density and abundance of macroinvertebrates, identified to family level, at 50 sites within Dhanmondi Lake, a heavily polluted sub‐tropical urban lake in Dhaka, Bangladesh. We investigated the associations of mussel density on different macroinvertebrate families, which we further classified into functional feeding groups (predators, scrapers, collectors and shredders).

We found that densities of the two mussel species were negatively correlated in the 1–3‐m nearshore zone; average density of Lamellidens was 46.4 ± SE 3.6 individuals/0.25 m2, and average density of Parreysia was 6.4 ± SE 1.4 individuals/0.25 m2. In total, 2319 Lamellidens and 320 Parreysia specimens were recorded. Sites containing higher densities of Lamellidens had greater similarity in macroinvertebrate community composition, while there was no effect for Parreysia. Particular macroinvertebrate families and functional feeding groups were also associated with mussels; the majority of significant associations were with Lamellidens but not Parreysia. The clearest associations were with predators and scrapers, which increased in abundance with Lamellidens density.

This provides support for a possible role for mussels in structuring freshwater invertebrate communities and emphasises the importance of species identity in these effects, with one possible keystone species (Lamellidens) largely accounting for mussel–invertebrate associations. While microhabitat variables (shading and sediment type) were poor predictors of abundance in any invertebrate taxa (including mussels), manipulative studies are needed to disentangle the direct effects of mussels from the role of overlapping habitat preference between mussels and other invertebrates.

Our results highlight the importance of species identity in patterns of community composition, particularly for ecosystem engineer species. We also reinforce the need to test the assumption of ecological redundancy within communities.
Ensilibility and protein degradation characteristics of forage from mountain grasslands containing tanniferous species
Authors: Ineichen Simon , Seiler Andrea B. , Wyss Ueli , Malisch Carsten S. , Reidy Beat 
Published: August 2023

AbstractEnsiling forage from species‐rich mountain grasslands is challenging. Low concentrations of fermentable carbohydrates and the coarse morphological structure of the forage promote the activity of butyric acid forming bacteria. This is associated with the formation of ammonia from protein degradation, resulting in an insufficient pH decline. On the other hand, forage from species‐rich swards may contain tanniferous plant species which contain varying contents of condensed tannins (CT). Therefore, the silage quality of forage prepared from species‐rich mountain grasslands and the role CT may play in silage fermentation was studied. A set‐up of two long‐term mineral fertilization field experiments, located in the Jura mountains and the Alps in Switzerland were used to obtain forage with contrasting species and chemical composition. Collection was done during both the generative and vegetative growth stage from three differently fertilized swards: unfertilised (“0”), fertilized with phosphorus and potassium (“PK”) or fertilized with PK and nitrogen (“NPK”). The forage was wilted to approximately 37% dry matter (DM), chopped to 2 cm lengths and ensiled for at least 65 days as laboratory‐scale silages. The wilted forage was characterized by concentrations of crude protein between 117 and 130 g/kg DM and water‐soluble carbohydrates varying from 84 to 148 g/kg DM. Concentrations of CT ranged from 6 g to 14 g/kg DM and those of soluble CT from 1.8 to 7.6 g/kg DM. All silages contained butyric acid, irrespective of the type of fertilization or harvest stage (range: 1.5 g to 16 g/kg DM). Concentrations of acetic and lactic acid ranged from 2.1 g to 15.0 g/kg DM and from 21.0 to 44.0 g/kg DM, respectively. Concentrations of unfermented sugar remained high and pH levels were above those expected. Formation of non‐protein‐N (NPN) increased in the range of 130 to 264 g/kg N from wilted to ensiled forage. The negative correlations of CT or soluble CT contents with ammonia‐N or NPN in silage were found in both forage from the generative and vegetative harvests indicating a possible relationship with protein degradation during ensiling.
Effects of PK‐guided prophylaxis on clinical outcomes and FVIII consumption for patients with moderate to severe Haemophilia A
Authors: Young Guy , Callaghan Michael U. , Balasa Vinod , Soni Amit , Ahuja Sanjay , Roberts Jonathan C. , Simpson Mindy L. , Kizilocak Hande , Frick Andrew , Mokdad Ali G. , Xing Shan , Caicedo Jorge 
Published: August 2023

AbstractIntroductionIn recent years, there has been increased focus on individualizing treatment for persons with hemophilia including pharmacokinetic‐guided (PK) dosing.AimsIn this retrospective study clinical outcomes before and after PK‐guided prophylaxis were examined.Materials and methodsEight Haemophilia Treatment Centres from the United States participated in the study and included 132 patients classified into two cohorts: those undergoing a PK‐assessment for product switch (switchers) or to optimize treatment (non‐switchers). Subset analyses for the two most common products and patients with dosing per prescription label were included for annual bleeding rates (ABR), mean weekly consumption outcomes, and annualized cost of prophylaxis.ResultsThe most common products before and after index date were octocog alfa, rurioctocog alfa pegol, and efmoroctocog alfa. Seventy‐four (56%) patients were identified as switchers and 58 (44%) patients were classified as non‐switchers. The majority of patients (78.0%) experienced either a decrease in ABR post‐index or maintained 0 ABR during pre‐ and post‐index time periods, with similar proportions identified in both switchers (77.0%) and non‐switchers (79.3%) populations. Non‐switchers were identified as having no significant change in cost of therapy, while switchers experienced increased cost of therapy driven by higher price of extended half‐life products. Within subset analyses, patients receiving rurioctocog alfa pegol and efmoroctocog alfa had mean ABR under 1 after index date.ConclusionPK‐guided prophylaxis has the potential to improve clinical outcomes without increase in cost of therapy for patients maintaining product and can aid in maintaining effective protection against bleeds in those switching product.
Emergency department patient‐centred care perspectives from deaf and hard‐of‐hearing patients
Authors: James Tyler G. , Sullivan Meagan K. , McKee Michael M. , Rotoli Jason , Maruca David , Stachowiak Rosemarie , Cheong JeeWon , Varnes Julia R. 
Published: August 2023

AbstractBackgroundDeaf and hard‐of‐hearing (DHH) patients are a priority population for emergency medicine health services research. DHH patients are at higher risk than non‐DHH patients of using the emergency department (ED), have longer lengths of stay in the ED and report poor patient–provider communication. This qualitative study aimed to describe ED care‐seeking and patient‐centred care perspectives among DHH patients.MethodsThis qualitative study is the second phase of a mixed‐methods study. The goal of this study was to further explain quantitative findings related to ED outcomes among DHH and non‐DHH patients. We conducted semistructured interviews with 4 DHH American Sign Language (ASL)‐users and 6 DHH English speakers from North Central Florida. Interviews were transcribed and analysed using a descriptive qualitative approach.ResultsTwo themes were developed: (1) DHH patients engage in a complex decision‐making process to determine ED utilization and (2) patient‐centred ED care differs between DHH ASL‐users and DHH English speakers. The first theme describes the social‐behavioural processes through which DHH patients assess their need to use the ED. The second theme focuses on the social environment within the ED: patients feeling stereotyped, involvement in the care process, pain communication, receipt of accommodations and discharge processes.ConclusionsThis study underscores the importance of better understanding, and intervening in, DHH patient ED care‐seeking and care delivery to improve patient outcomes. Like other studies, this study also finds that DHH patients are not a monolithic group and language status is an equity‐relevant indicator. We also discuss recommendations for emergency medicine.Patient or Public ContributionThis study convened a community advisory group made up of four DHH people to assist in developing research questions, data collection tools and validation of the analysis and interpretation of data. Community advisory group members who were interested in co‐authorship are listed in the byline, with others in the acknowledgements. In addition, several academic‐based co‐authors are also deaf or hard of hearing.
Anastomosing haemangioma of the adrenal gland: A clinicopathological series of seven cases
Authors: Alaghehbandan Reza , Remer Erick M , Berber Eren , McKenney Jesse K 
Published: August 2023

AimsAnastomosing haemangioma is a rare benign vascular neoplasm that may histologically mimic angiosarcoma. We report the largest single institution series of anastomosing haemangioma in the adrenal gland with emphasis on clinical and radiological features.Methods and resultsOur laboratory information system was searched for a 25‐year period (1999–2023), yielding seven cases confirmed as anastomosing haemangioma of the adrenal gland after pathological re‐review. Clinical, radiological and pathological information was obtained from medical charts and submitting pathologists. Of a total of seven patients, four (57.1%) were men and three women, ranging in age from 37 to 75 years (mean = 61). Six of seven patients underwent adrenalectomies and one had radical nephrectomy. Tumours ranged from 0.7 to 6.4 cm (mean = 2.1 cm) and five of seven (71%) were grossly well‐circumscribed. Five of seven lesions were found incidentally at imaging for other indications. All tumours were unifocal except one, which presented with multifocal disease with a concurrent adjacent retroperitoneal anastomosing haemangioma. Three of five tumours imaged with contrast enhancement were almost completely hyperenhancing with a small central non‐enhancing portion, features overlapping with pheochromocytoma. One of seven tumours involved the peri‐adrenal adipose tissue with a focally infiltrative pattern. There were no recurrences or metastases in six patients with available follow‐up data (median = 95 months).ConclusionsBenign anastomosing haemangiomas of the adrenal gland tend to occur in older patients, may mimic pheochromocytoma on imaging and must be distinguished from angiosarcoma pathologically. Better awareness of this entity by pathologists, radiologists and surgeons is crucial to appropriate work‐up, diagnosis and management.
Microbes mediated immunogenic cell death in cancer immunotherapy
Authors: Huang Jumin , Duan Fugang , Xie Chun , Xu Jiahui , Zhang Yizhong , Wang Yuwei , Tang Yu‐Ping , Leung Elaine Lai‐Han 
Published: August 2023

SummaryImmunogenic cell death (ICD) is one of the 12 distinct cell death forms, which can trigger immune system to fight against cancer cells. During ICD, a number of cellular changes occur that can stimulate an immune response, including the release of molecules called damage‐associated molecular patterns (DAMPs), signaling to immune cells to recognize and attack cancer cells. By virtue of their pivotal role in immune surveillance, ICD‐based drug development has been a new approach to explore novel therapeutic combinations and personalized strategies in cancer therapy. Several small molecules and microbes can induce ICD‐relevant signals and cause cancer cell death. In this review, we highlighted the role of microbe‐mediate ICD in cancer immunotherapy and described the mechanisms through which microbes might serve as ICD inducers in cancer treatment. We also discussed current attempts to combine microbes with chemotherapy regimens or immune checkpoint inhibitors (ICIs) in the treatment of cancer patients. We surmise that manipulation of microbes may guide personalized therapeutic interventions to facilitate anticancer immune response.
Clearance phagocytosis by the retinal pigment epithelial during photoreceptor outer segment renewal: Molecular mechanisms and relation to retinal inflammation
Authors: Lieffrig Stephanie A. , Gyimesi Gavin , Mao Yingyu , Finnemann Silvia C. 
Published: August 2023

SummaryMammalian photoreceptor outer segment renewal is a highly coordinated process that hinges on timed cell signaling between photoreceptor neurons and the adjacent retinal pigment epithelial (RPE). It is a strictly rhythmic, synchronized process that underlies in part circadian regulation. We highlight findings from recently developed methods that quantify distinct phases of outer segment renewal in retinal tissue. At light onset, outer segments expose the conserved “eat‐me” signal phosphatidylserine exclusively at their distal, most aged tip. A coordinated two‐receptor efferocytosis process follows, in which ligands bridge outer segment phosphatidylserine with the RPE receptors αvβ5 integrin, inducing cytosolic signaling toward Rac1 and focal adhesion kinase/MERTK, and with MERTK directly, additionally inhibiting RhoA/ROCK and thus enabling F‐actin dynamics favoring outer segment fragment engulfment. Photoreceptors and RPE persist for life with each RPE cell in the eye servicing dozens of overlying photoreceptors. Thus, RPE cells phagocytose more often and process more material than any other cell type. Mutant mice with impaired outer segment renewal largely retain functional photoreceptors and retinal integrity. However, when anti‐inflammatory signaling in the RPE via MERTK or the related TYRO3 is lacking, catastrophic inflammation leads to immune cell infiltration that swiftly destroys the retina causing blindness.
Comparison of clinical outcomes, demographic, and laboratory characteristics of hospitalized COVID‐19 patients during major three waves driven by Alpha, Delta, and Omicron variants in Tehran, Iran
Authors: heydarifard Zahra , Shafiei‐Jandaghi Nazanin‐Zahra , Safaei Moslem , Tavakoli Forough , Shatizadeh Malekshahi Somayeh 
Published: August 2023

AbstractIntroductionThis study is the first study in which demographic, laboratory data, and outcomes of coronavirus disease‐2019 (COVID‐19) patients due to the circulating SARS‐CoV‐2 infections caused by different variants (Alpha, Delta, and Omicron) are compared in Iran.MethodsWe conducted a retrospective study of confirmed hospitalized COVID‐19 cases from April 9, 2021, to May 22, 2022. Demographic data and laboratory findings were extracted from patients' electronic medical records on the first day of admission to the hospital. All patients were followed up for outcomes related to COVID‐19 including intensive care unit (ICU) admission and mortality rate.ResultsOf 760 confirmed hospitalized COVID‐19 cases, 362, 298, and 100 represented patients during waves 4–6, respectively. During the Omicron wave, hospitalized patients were older than the other two waves and had a lower median level of C‐reactive protein (CRP), alanine transaminase (ALT), aspartate transaminase (AST), and erythrocyte sedimentation rate (ESR). The median length of hospital stay during waves 4–6 was 5 days (interquartile range [IQR]: 4.0–8.0), 7 days (IQR: 6.0–11), and 6 days (IQR: 5.0–9.0), respectively (p < 0.001). The rate of ICU admission during waves 4–6 significantly increased.ConclusionsAlthough the Omicron variant caused less severe disease, in older patients who were hospitalized due to Omicron infection, longer hospital and ICU stays were reported, which could be attributed to their old age. In particular, elderly patients are more vulnerable to severe COVID‐19; otherwise, as expected, other laboratory parameters and clinical outcomes were in accordance with differences in pathogenicity and infectivity of these variants.