bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disposition of Tablet and Capsule Formulations of Digoxin in the Elderly
Authors: Hui James , Wang Yow‐Ming C. , Chandrasekaran Appavu , Geraets Douglas R. , Caldwell James H. , Robertson Larry W. , Reuning Richard H. 
Published: October 2023

Study Objective. To compare digoxin tablets and liquid‐filled capsules with respect to excretion of the drug and its metabolites in urine and feces at steady state.Design. A randomized, crossover trial, each period lasting 3 weeks, with no washout period.Setting. A university hospital.Patients. Six patients, five of whom were elderly, with histories of gastrointestinal disorders, such as hypochlorhydria, intestinal bacterial overgrowth, and inflammatory bowel disease.Interventions. The patients received digoxin once/day in either tablet or capsule form for 3 weeks, and then were switched to the other formulation. Total urinary and fecal excretion from the last 3 days of each regimen were analyzed for the drug and metabolites.Measurements and Main Results. No statistically significant differences were found between tablets and capsules in recovery of digoxin or its metabolites in urine or feces (p=0.05). One subject had a 4‐fold increase in urinary drug excretion and 50% decrease in fecal excretion after taking the capsules compared with tablets. Intersubject variability in extent and type of metabolite excretion was greater than intrasubject variability.Conclusions. Fecal analyses may be an accurate way to classify patients as formers of digoxin reduction products.
Dose Evaluation Study of Alprostadil in Erectile Dysfunction
Authors: DA SILVA JOSE PEREIRA 
Published: October 2023

ABSTRACT: Intracavernous injection of vasoactive drugs is an important therapeutic advance for the treatment of erectile dysfunction. Namely three drugs used alone or in combination have gained clinical acceptance: papaverine, papaverine and phentolamine, and alprostadil.Since the first reports on the use of alprostadil in 1987, investigators of many countries published studies reporting the efficacy of alprostadil in inducing erections with tolerable local side‐effects. Based on his personal experience, methodology, and support to the patients who entered a self‐injection program, the author performed a formal dose evaluation study in 116 patients who self‐injected alprostadil for treatment of erectile dysfunction.Of the 296 patients seen during the years of 1988 to 1992 and who were eligible for self‐injection of alprostadil to maintain their capacity for intercourse, only 116 patients were entered in the selfinjection program. Their ages were between 27 and 69 years old (average 53). One hundred eleven (94.8%) have elected a dose equal or inferior to 20 mcg of alprostadil as the minimal dose producing complete and functional erections. The optimal dose range is decided for each patient based on his satisfaction and tolerance and includes erections of 1 to 2 hours long, without adverse systemic or local reactions. The side effects were minimal (16 cases = 13.78%). They were hematoma (12), prolonged erection (2), fibrosis with penile curvature (1), and dizziness (1). The results are similar to others related in previous literature.The author believes that intracavernous injection of vasoactive drugs is an important instrument to deal with impotence and alprostadil is the drug of choice for the self‐injection program. Longterm use of alprostadil and its effects, social acceptability, and its adoption by national health authorities are, according to the author, issues that need to be addressed.
Microsurgical Vasovasostomy
Authors: FOX MILES 
Published: October 2023

ABSTRACT: Over 3% of patients who have had a vasectomy now ask for reversal of their sterility in the United Kingdom, with divorce rates of more than one in three. Patency rates following vaso/asostomy using the usual methods with either no magnification or a loupe commonly result in patency rates of about 60–65% with ensuing fertility in about half of these cases. The thick‐walled vas has a lumen diameter of less than 1 mm, and there is often considerable disparity between proximal and distal ends resulting in obstruction as a major cause of failure. Division in the convoluted part of the vas, which is not uncommon, makes anastomosis even more difficult. Only accurate microsurgical anastomosis will consistently create optimal conditions for continuity without stenosis or leakage.The present paper describes the technique used and outcome of patency and fertility obtained in a personal series of the first 103 cases of microsurgical vasovasostomy, employing a two‐layer anastomosis carried out over a 5‐year period between 1 and 6 years ago. Ten had had a failed reversal operation elsewhere. A two‐layer microsurgical method of end‐to‐end anastomosis was employed, using a fine intraluminal nylon splint as a guide, which was withdrawn before the last interrupted suture was tied. Initially 8/0 Vicryl was used, and subsequently, with more experience, 10/0 Ethilon was employed.Sperm in the ejaculate was achieved in the whole series of bilateral primary operations in 85% rising to 94% with the use of 10/0 suture material and more experience. The patency results obtained match well those of previous microsurgical series, the largest recent one of Belker et al (1991) reporting 86% patency from five institutions, similar to whether a two‐layer or a modified one‐layer anastomosis was employed. However, a two‐layer anastomosis with approximation of the mucosa first is likely to attain more accurate results, particularly in the presence of disparity between the distal and proximal lumina, which is the usual finding (Owen and Kapila, 1984; Silber, 1988). It is for this reason that the two‐layer method was employed, and the results have been very gratifying with the patency rates achieved.Sperm concentration, quality, and motility improved in half the patients over the next 12 months. Fertility over a range of 12 months to 6 years postoperatively was 64% if vasectomy had been performed less than 10 years before, and 39% if 10 years or more had elapsed. In patients with previously failed reversal attempts elsewhere, 40% attained sperm in the ejaculate and half of these became fertile.The additional time and effort required for a microsurgical approach to vasovasostomy were worthwhile to obtain these results.
Combined colour deconvolution and artificial intelligence approach for region‐selective immunohistochemical labelling quantification: The example of alpha smooth muscle actin in mouse kidney
Authors: Luchian Andreea , Ressel Lorenzo 
Published: October 2023

AbstractImmunohistochemical (IHC) localisation of protein expression is a widely used tool in pathology. This is semi‐quantitative and exhibits substantial intra‐ and inter‐observer variability. Digital approaches based on stain quantification applied to IHC are precise but still operator‐dependent and time‐consuming when regions of interest (ROIs) must be defined to quantify protein expression in a specific tissue area. This study aimed at developing an IHC quantification workflow that benefits from colour deconvolution for stain quantification and artificial intelligence for automatic ROI definition. The method was tested on 10 whole slide images (WSI) of alpha‐smooth muscle actin (aSMA) stained mouse kidney sections. The task was to identify aSMA‐positive areas within the glomeruli automatically. Total aSMA detection was performed using two channels (DAB, haematoxylin) colour deconvolution. Glomeruli segmentation within the same IHC WSI was performed by training a convolutional neural network with annotated examples of glomeruli. For both aSMA and glomeruli, binary masks were created. Co‐localisation was performed by overlaying the masks and assigning red/green colours, with yellow indicative of a co‐localised signal. The workflow described and exemplified using the case of aSMA expression in glomeruli can be applied to quantify the expression of IHC markers within different structures of immunohistochemically stained slides. The technique is objective, has a fully automated threshold approach (colour deconvolution phase) and uses AI to eliminate operator‐dependent steps.
PortPred: Exploiting deep learning embeddings of amino acid sequences for the identification of transporter proteins and their substrates
Authors: Anteghini Marco , Santos Vitor AP Martins dos , Saccenti Edoardo 
Published: October 2023

AbstractThe physiology of every living cell is regulated at some level by transporter proteins which constitute a relevant portion of membrane‐bound proteins and are involved in the movement of ions, small and macromolecules across bio‐membranes. The importance of transporter proteins is unquestionable. The prediction and study of previously unknown transporters can lead to the discovery of new biological pathways, drugs and treatments. Here we present PortPred, a tool to accurately identify transporter proteins and their substrate starting from the protein amino acid sequence. PortPred successfully combines pre‐trained deep learning‐based protein embeddings and machine learning classification approaches and outperforms other state‐of‐the‐art methods. In addition, we present a comparison of the most promising protein sequence embeddings (Unirep, SeqVec, ProteinBERT, ESM‐1b) and their performances for this specific task.
Anatomical and physiological adaptation of the scrotal artery with muscular reinforcement in the middle layer and connective reinforcement of the adventitia
Authors: Rodríguez Héctor , Arriaza Camilo , Sarabia Luis , Espinoza‐Navarro Omar 
Published: October 2023

AbstractThe histology of blood vessels shows they are structured in three layers or tunics: tunica intima, which includes the internal limiting lamina with high elastin content; tunica media of smooth muscles fibers of circular disposition, which includes the external limiting lamina; and tunica adventitia of connective tissue. The vascular system is essential in regulating body temperature, especially in the scrotum and testis. This study aimed to analyze the histology of the scrotal arteries and their possible relationship to testicular temperature homeostasis. This study used scrotal samples from human adults, anonymized and obtained from the University of Chile's teaching bank. The control group corresponds to an arteriole of muscle tissue. The results show that the middle layer of the scrotal artery is made up of smooth muscle fibers distributed in two layers: a longitudinal inner sublayer and a circular outer sublayer, different from the findings in muscle tissue arteries, with a single, circularly arranged muscle layer. This arrangement could be related to testicular temperature homeostasis by reducing the temperature of the testis and seminiferous tubules. The results described in this work suggest that these anatomical adaptations may be very significant in the face of the constant increase in global temperature. Further and better research is required to understand the mechanisms of thermoregulation in human reproduction and the histological particularities of the tissues that form the scrotum.Research Highlights
The human scrotal artery has a histological composition adapted for regulation of testicular temperature.
The muscular double middle layer of the scrotal artery retains intravascular temperature.
Distribution and developmental changes of IL‐21 immunopositive cells in the bursa of Fabricius of Jinhu silky chicken
Authors: Ke Yanyan , Khaliq Haseeb , Jiafu Lin , Waqas Muhammad Yasir , Javid Muhammad Arshad , Basit Muhammad Abdul , Bhatti Sheraz Ahmed , Saleem Muhammad Usman , Farooq Abdul Asim , Murtaza Saeed 
Published: October 2023

AbstractBursa of Fabricius (BOF) is a unique immune organ of birds. It is the place where lymphocytes develop, differentiate and mature. Young chicken BOF is susceptible to infection and damage, and even atrophy, causing immune suppression, and bringing huge economic losses to chicken production. Therefore, studying the regulatory mechanism of chicken bursa development is of great practical significance for disease prevention and diagnosis. Jinhu silky chicken (JSC) is a local excellent breed in the Fujian Province of China and with strong disease resistance. However, studies on the disease resistance of JSC are scarce. This study aimed to provide a theoretical basis for reproduction and disease control of JSC. Developmental features of the structure and the IL‐21‐positive cell (IL‐21 PC) distribution on the BOF in JSC were measured from 7 to 300 days of age. Bursas of chicken (n = 36) were taken at 7, 35, 70, 150, 240, and 300 days of age for preparation of paraffin sections and stained with hematoxylin–eosin (HE) and immunohistochemistry. The microstructure of JSC's BOF was similar to that of other poultry. The cortical‐medullary boundary of the bursa nodule was not obvious at 7 days of age, but it was evident after 35 days of age. Before 70 days of age, IL‐21 positive cells (PC) were scattered on the BOF. At 150 days of age, the number of IL‐21 PC in the bursa were the highest and the nuclei were clear. The level of IL‐21 PC gradually decreased with age. The BOF degenerated and disappeared in 300‐day‐old JSC. The histological structure of the BOF was similar to that of other poultry. IL‐21 PC were widespread in the BOF at different ages, but the numbers were different.
Transcriptional background effects on a tumor driver gene in different pigment cell types of medaka
Authors: Abdulsahib Shahad , Boswell William , Boswell Mikki , Savage Markita , Schartl Manfred , Lu Yuan 
Published: October 2023

AbstractThe Xiphophorus melanoma receptor kinase gene, xmrk, is a bona fide oncogene driving melanocyte tumorigenesis of Xiphophorus fish. When ectopically expressed in medaka, it not only induces development of several pigment cell tumor types in different strains of medaka but also induces different tumor types within the same animal, suggesting its oncogenic activity has a transcriptomic background effect. Although the central pathways that xmrk utilizes to lead to melanomagenesis are well documented, genes and genetic pathways that modulate the oncogenic effect and alter the course of disease have not been studied so far. To understand how the genetic networks between different histocytes of xmrk‐driven tumors are composed, we isolated two types of tumors, melanoma and xanthoerythrophoroma, from the same xmrk transgenic medaka individuals, established the transcriptional profiles of both xmrk‐driven tumors, and compared (1) genes that are co‐expressed with xmrk in both tumor types, and (2) differentially expressed genes and their associated molecular functions, between the two tumor types. Transcriptomic comparisons between the two tumor types show melanoma and xanthoerythrophoroma are characterized by transcriptional features representing varied functions, indicating distinct molecular interactions between the driving oncogene and the cell‐type‐specific transcriptomes. Melanoma tumors exhibit gene signatures that are relevant to proliferation and invasion, while xanthoerythrophoroma tumors are characterized by expression profiles related to metabolism and DNA repair. We conclude the transcriptomic backgrounds, exemplified by cell‐type‐specific genes that are downstream of xmrk effected signaling pathways, contribute the potential to change the course of tumor development and may affect overall tumor outcomes.
Toward depathologizing queerness: An analysis of queer oppression in clinical genetics
Authors: Berro Tala , Zayhowski Kimberly 
Published: October 2023

AbstractCritically examining the way that the field of clinical genetics has impacted queer communities offers the field an opportunity to strengthen our commitment to inclusive high‐quality care to all patients, families, and communities. This article reviews the origins of clinical genetics and genetic counseling in the eugenics movement and how this ontology promoted harmful medical practices grounded in assumptions of what is “normal.” We critically examine existing clinical genetics practices and how commonly used binary frameworks for gender, sex, and sexuality perpetuate heteronormative, cisnormative, and bioessentialist assumptions. In order to move toward queer inclusivity, the genetic counseling field must first take accountability for past injustices. Restorative justice and trauma‐informed approaches offer a way to engage with the queer community and to begin to rectify the history of medical harm. Through our analysis, we advocate for expanding efforts to depathologize queerness, promote bodily autonomy, and provide equitable healthcare for the queer community.
Hospital‐based opioid treatment: Expanding and sustaining the model in Texas
Authors: Moriates Christopher , Boulton Alanna , Walker Blair , Holliman Rachel , Christian Nicholaus , Weems John , Humphry Emily , Young Sara , Bottner Richard , Potter Jennifer 
Published: October 2023

AbstractThis Brief Report includes follow‐up data about the sustainability and expansion of the Buprenorphine Team (B‐Team), a hospital‐based opioid treatment (HBOT) program. Between September 2018 and January 2023, the B‐Team started 398 patients with opioid‐use disorder (OUD) on buprenorphine therapy and coordinated outpatient care for 353 patients before discharge. Two‐hundred and forty‐nine of these patients were scheduled for follow‐up at our partner addiction treatment clinic. Retention rates at our partner clinic remain relatively high: 73 patients (36% of eligible patients) continued to attend appointments between 6 and 12 months, and 40 of 180 patients (22%) who have been discharged from the hospital for at least 1 year continued to attend appointments. This model has been adopted at three additional Texas hospitals, resulting in rapid growth: 1037 patients were started on buprenorphine across these four sites during 2021–2022. Our longitudinal results support HBOT as an effective model for treating patients with OUD.
Deep Learning‐Driven Transformation: A Novel Approach for Mitigating Batch Effects in Diffusion MRI Beyond Traditional Harmonization
Authors: Wada Akihiko , Akashi Toshiaki , Hagiwara Akifumi , Nishizawa Mitsuo , Shimoji Keigo , Kikuta Junko , Maekawa Tomoko , Sano Katsuhiro , Kamagata Koji , Nakanishi Atsushi , Aoki Shigeki 
Published: October 2023

Background“Batch effect” in MR images, due to vendor‐specific features, MR machine generations, and imaging parameters, challenges image quality and hinders deep learning (DL) model generalizability.PurposeWe aim to develop a DL model using contrast adjustment and super‐resolution to reduce diffusion‐weighted images (DWIs) diversity across magnetic field strengths and imaging parameters.Study TypeRetrospective.SubjectsThe DL model was built using an open dataset from one individual. The MR machine identification model was trained and validated on a dataset of 1134 adults (54% females, 46% males), with 1050 subjects showing no DWI abnormalities and 84 with conditions like stroke and tumors. The 21,000 images were divided into 80% for training, 20% for validation, and 3500 for testing.Field Strength/SequenceSeven MR scanners from four manufacturers with 1.5 T and 3 T magnetic field strengths. DWIs were acquired using spin‐echo sequences and high‐resolution T2WIs using the T2‐SPACE sequence.AssessmentAn experienced, board‐certified radiologist evaluated the effectiveness of restoring high‐resolution T2WI and harmonizing diverse DWI with metrics such as PSNR and SSIM, and the texture and frequency attributes were further analyzed using gray‐level co‐occurrence matrix and 1‐dimensional power spectral density. The model's impact on machine‐specific characteristics was gauged through the performance metrics of a ResNet‐50 model. Comprehensive statistical tests were employed for statistical robustness, including McNemar's test and the Dice index.ResultsOur DL protocol reduced DWI contrast and resolution variation. ResNet‐50 model's accuracy decreased from 0.9443 to 0.5786, precision from 0.9442 to 0.6494, recall from 0.9443 to 0.5786, and F1 score from 0.9438 to 0.5587. The t‐SNE visualization indicated more consistent image features across multiple MR devices. Autoencoder halved learning iterations; Dice coefficient >0.74 confirmed signal reproducibility in 84 lesions.ConclusionThis study presents a DL strategy to mitigate batch effects in diffusion MR images, improving their quality and generalizability.Evidence Level3Technical EfficacyStage 1
Temporal and structural patterns of hepatitis B virus integrations in hepatocellular carcinoma
Authors: Ren Haozhen , Chen Xun , Wang Jinglin , Chen Ying , Hafiz Alex , Xiao Qian , Fu Shiwei , Madireddy Advaitha , Li Wei Vivian , Shi Xiaolei , Cao Jian 
Published: October 2023

AbstractChronic infection of hepatitis B virus (HBV) is the major cause of hepatocellular carcinoma (HCC). Notably, 90% of HBV‐positive HCC cases exhibit detectable HBV integrations, hinting at the potential early entanglement of these viral integrations in tumorigenesis and their subsequent oncogenic implications. Nevertheless, the precise chronology of integration events during HCC tumorigenesis, alongside their sequential structural patterns, has remained elusive thus far. In this study, we applied whole‐genome sequencing to multiple biopsies extracted from six HBV‐positive HCC cases. Through this approach, we identified point mutations and viral integrations, offering a blueprint for the intricate tumor phylogeny of these samples. The emergent narrative paints a rich tapestry of diverse evolutionary trajectories characterizing the analyzed tumors. We uncovered oncogenic integration events in some samples that appear to happen before and during the initiation stage of tumor development based on their locations in reconstituted trajectories. Furthermore, we conducted additional long‐read sequencing of selected samples and unveiled integration‐bridged chromosome rearrangements and tandem repeats of the HBV sequence within integrations. In summary, this study revealed premalignant oncogenic and sequential complex integrations and highlighted the contributions of HBV integrations to HCC development and genome instability.
Cultivating Creative Problem‐Solving Skills in a Strategic Communication Class: Student Perceptions of a Collaborative Assignment
Authors: Hether Heather J. 
Published: October 2023

ABSTRACTProblem‐solving is an essential undergraduate learning outcome that also supports students' professional success. The creative problem‐solving model (CPS) (Isaksen et al., 2011) facilitates the development of these skills and aligns well with the scope of public relations (PR). The current study investigates student perceptions of an assignment anchored in the CPS model, designed to support their problem‐solving skills in a collaborative context. Survey findings of students enrolled in an upper division PR course (N = 42) indicate students enjoyed generating ideas and developing solutions and found these stages also supported their learning the most. However, not all students benefitted similarly from the assignment. There were differences associated with gender and race/ethnicity. Student enjoyment, comfort, and team dynamics were also important predictors of perceived learning. Findings from this study have implications for future research and development of undergraduate learning opportunities.