bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of circular stapler size on the risk of anastomotic stricture following total mesorectal excision in rectal cancer patients: A retrospective cross‐sectional study
Authors: Behboudi Behnam , Ahmadi‐Tafti Seyed‐Mohsen , Hosseini Seyyed‐Alireza , Tadbir‐Vajargah Kiana , Fazeli Mohammad Sadegh , Hadizadeh Alireza , Poopak Amirhossein , Keramati Mohammad Reza , Kazemeini Alireza , Ayati Aryan , Yousefi‐Koma Hannaneh
Published: October 2023

Introduction

Colorectal cancer (CRC) surgery complications are a major issue affecting morbidity and mortality rates. Anastomotic stricture, which occurs in almost 30% of patients after surgery for rectal cancer, is one of the most serious but underreported side effects. In this study, we tried to assess the effect of stapler size on anastomotic stricture rate.

Materials and Methods

At our facility, all patients underwent low anterior resections (LAR) performed using an open laparotomy technique. A contour‐curved stapler and an end‐to‐end anastomosis (EEA) circular stapler were used in the double stapling technique (DST). All patients also underwent a protective loop ileostomy. Patients who developed stricture following leakage were excluded.

Results

This study comprised a total of 173 rectal cancer patients. A 29‐mm circle stapler was used to anastomose 77 patients (44.5%), while a 31‐mm circular stapler was used to anastomose 96 patients (55.5%). Six individuals experienced strictures; two had a 29 mm stamper and four (4.4%) had a 31 mm one. There was no significant difference between the two groups (p:0.575). On aggregate, 8 patients experienced leakage; 3 (3.8%) of these patients received treatment with a 29 mm stapler, whereas 5 (5.2%) received treatment with a 31 mm stapler.

Conclusion

this study found no statistically significant difference in the stricture rates and stapler size. The findings of this study provide credibility to the notion that in rectal cancer patients having LAR, strictures can be safely avoided by performing the anastomoses with both staplers.
Dendritic cell immunoreceptor 2 (DCIR2) deficiency decreases hepatic conventional dendritic cell content but not the progression of diet‐induced obesity
Authors: Bellini Rossella , Moregola Annalisa , Nour Jasmine , Uboldi Patrizia , Bonacina Fabrizia , Norata Giuseppe D.
Published: October 2023

Aims

Inflammatory pathways and immune system dysregulation participate in the onset and progression of cardiometabolic diseases. The dendritic cell immunoreceptor 2 (DCIR2) is a C‐type lectin receptor mainly expressed by conventional type 2 dendritic cells, involved in antigen recognition and in the modulation of T cell response. Here, we investigated the effect of DCIR2 deficiency during the development of obesity.

Methods

DCIR2 KO mice and the WT counterpart were fed with high‐fat diet (HFD) for 20 weeks. Weight gain, glucose and insulin tolerance were assessed, parallel to immune cell subset profiling and histological analysis.

Results

After HFD feeding, DCIR2 KO mice presented altered conventional dendritic cell distribution within the liver without affecting markers of hepatic inflammation. These observations were liver restricted, since immune profile of metabolic and lymphoid organs‐namely adipose tissue, spleen and mesenteric lymph nodes‐did not show differences between the two groups. This reflected in a similar metabolic profile of DCIR2 KO compared to WT mice, characterized by comparable body weight gain as well as adipose tissues, spleen, Peyer's patches and mesenteric lymph nodes weight at sacrifice. Also, insulin response was similar in both groups.

Conclusion

Our data show that DCIR2 has a redundant role in the progression of diet‐induced obesity and inflammation.
Association of IL‐17 and IL‐27 polymorphisms with susceptibility to recurrent pregnancy loss and pre‐eclampsia: A systematic review and meta‐analysis
Authors: Ma Yue , Ma Mingyue , Ye Shenglong , Liu Yuanying , Zhao Xueqing , Wang Yongqing
Published: October 2023

Objective

Recurrent pregnancy loss (RPL) and pre‐eclampsia (PE) are immune‐related pregnancy complications that have been linked to CD4+ T cells and their cytokines, which can be influenced by genetic polymorphisms. This meta‐analysis aimed to investigate the relationship between interleukin (IL)‐17 and ‐27 polymorphisms and the susceptibility to RPL and PE.

Methods

All eligible case‐control studies published up to February 2023 were identified by searching PubMed, EMBASE, Cochrane, Web of Science, and Google Scholar. The risk of recurrent pregnancy loss and PE associated with the IL‐17 rs2275913, IL‐17 rs763780, IL‐27 rs153109, and IL‐27 rs17855750 polymorphisms were estimated for each study.

Results

The meta‐analysis incorporated a total of 13 studies. The overall analysis indicated that IL‐17 rs2275913, IL‐17 rs763780, IL‐27 rs153109, and IL‐27 rs17855750 polymorphisms were not significantly associated with immune‐related pregnancy complications, including RPL and PE. However, when the analysis was stratified by disease type, the IL‐17 rs2275913 polymorphism was found to be associated with an increased risk of RPL (recessive model AA/GA + GG: OR = 1.68, 95% confidence interval [CI]: 1.13–2.49, p = .01).

Conclusions

The IL‐17 rs763780, IL‐27 rs153109, and IL‐27 rs17855750 polymorphisms were not significantly associated with RPL and PE, whereas the IL‐17 rs2275913 polymorphism was associated with the susceptibility to recurrent miscarriage.
The role of inflammatory factors and T‐cell subsets in the diagnosis of recurrence in epithelial ovarian cancer patients and the effect of olaparin treatment on them
Authors: Maowulieti Gulijianati , Zhao Shaojie , Zhao Min , Yuan Hua
Published: October 2023

Background

The aim of the study is to investigate the role of serum inflammatory factors and T‐cell subsets in the diagnosis of recurrence in epithelial ovarian cancer patients and the effect of olaparib on inflammatory factor and T‐lymphocyte subsets in patients with recurrent epithelial ovarian cancer.

Methods

In this study, 100 patients diagnosed as recurrent epithelial ovarian cancer in our hospital and 100 patients without recurrent epithelial ovarian cancer in the same period were selected. According to the treatment plan, the recurrent patients were divided into conventional therapy group (Paclitaxel and Carboplatin) and combined therapy group (Paclitaxel, Carboplatin, and olaparib). The levels of serum inflammatory factors were evaluated by enzyme‐linked immunosorbent assay. The peripheral blood T‐lymphocyte subsets in each group were detected by flow cytometry.

Results

Compared with nonrecurrent patients, recurrent patients have higher serum interleukin‐6 (IL‐6) and tumor necrosis factor‐α (TNF‐α) levels (p < .05), and lower interferon‐γ (IFN‐γ) level and the CD4+/CD8+ ratio. After adjusting for confounding factors, the results showed that the serum IL‐6, IFN‐γ, and TNF‐α levels were influencing factors of recurrence in epithelial ovarian cancer patients. The area under the receiver operating curve and the sensitivity of serum TNF‐α in predicting ovarian cancer recurrence were higher than those of IL‐6 and IFN‐γ. After secondary chemotherapy and/or olaparib maintenance treatment, the IL‐6 (p < .001) and TNF‐α (p < .001) levels in combined therapy group were lower than those in the conventional therapy, whereas the IFN‐γ level (p < .001), the CD4+ T‐cell proportion (p = .0069) and the CD4+/CD8+ ratio (p = .0201) were higher than those in the conventional therapy.

Conclusion

The serum IL‐6, TNF‐α, and IFN‐γ levels were closely related to the recurrence of ovarian cancer. Olaparib maintenance treatment can significantly decrease the IL‐6 and TNF‐α level, and increase IFN‐γ level and the CD4+/CD8+ ratio in patients with recurrent ovarian cancer.
Regulation of cell proliferation and transdifferentiation compensates for ventilator‐induced lung injury mediated by NLRP3 inflammasome activation
Authors: Liu Huan , Yang Xuepeng , Liu Ge
Published: October 2023

Background

Mechanical ventilation is an important means of respiratory support and treatment for various diseases. However, its use can lead to serious complications, especially ventilator‐induced lung injury (VILI). The mechanisms underlying this disease are complex, but activation of inflammatory signalling pathways results in activation of cytokines and inflammatory mediators, which play key roles in VILI. Recent studies have demonstrated that nod‐like receptor protein 3 (NLRP3) inflammasome activation mediates VILI and also accompanied by cell proliferation and transdifferentiation to compensate for alveolar membrane damage. Type I alveolar epithelial cells (AECs I), which are involved in the formation of the blood‐air barrier, are vulnerable to damage but cannot proliferate by themselves; thus, replacing AECs I relies on type II alveolar epithelial cells (AECs II).

Objective

The review aims to introduce the mechanisms of NLRP3 inflammasome activation and its inhibitors, as well as the mechanisms that regulate cell proliferation and transdifferentiation.

Methods

A large number of relevant literature was searched, then the key content was summarized and figures were also made.

Results

The mechanism of NLRP3 inflammasome activation has been further explored, including but not limited to pathogenic and aseptic inflammatory signals, such as, pathogenic molecular patterns and host‐derived danger‐associated molecular patterns activate toll‐like receptor 4/nuclear factor‐kappaB pathway or reactive oxygen species, cyclic stretch, adenosine triphosphate induce K+ efflux through P2X7, Ca2+ inflow, mitochondrial damage, etc, eventually induce NIMA‐related kinase 7/NLRP3 binding and NLRP3 inflammasome activation. Not only that, the review also described in detail the inhibitors of NLRP3 inflammasome. And the mechanisms regulating cell proliferation and transdifferentiation are complex and unclear, including the Wnt/β‐catenin, Yap/Taz, BMP/Smad and Notch signalling pathways.

Conclusions

NLRP3 inflammasome activation mediated VILI, and VILI is alleviated after interfering with its activation, and inflammation and repair exist simultaneously in VILI. Clarifying these mechanisms is expected to provide theoretical guidance for alleviating VILI by inhibiting the inflammatory response and accelerating alveolar epithelial cell regeneration in the early stage.
Revisiting corporate governance and financial risk‐taking
Authors: Alzayed Noora , Eskandari Rasol , Eshraghi Arman , Yazdifar Hassan
Published: October 2023

Corporate governance attributes have varying effects on risk taking when variables are examined separately. We study the effects of a large range of corporate governance attributes on risk taking using a comprehensive US sample. Our findings confirm that although there are certain characteristics that drive this positive effect such as compensation structure, there are those which have the opposite effect such as board‐level attributes. Our paper contributes to the broader literature on the relationship between corporate governance and risk in financial institutions, which are often overlooked in traditional studies. We shed light on the importance of studying corporate governance at a granular level rather than using a single index. The findings offer insights to regulators in determining suitable corporate governance frameworks to ensure the protection of investors rights in financial institutions.
Developing Drug Use Evaluation Criteria for Parenteral Fluoroquinolones
Authors: Guay David R. P. , Covington Tim R. , Alexander Vance L.
Published: October 2023

The basic tenet of pharmaceutical care asserts that the delivery of optimal, cost‐effective pharmacotherapy can be best achieved by identifying, resolving, and preventing drug‐related problems. Drug use evaluation (DUE) is one of the primary tools used to achieve these ends. Fluoroquinolone antimicrobials meet Joint Commission criteria for targeting for DUE: the drugs are used in populations at high risk for adverse drug reactions, quality assurance or infection control committees target them for DUE, the drugs are costly, they may be suspected or known to be used inappropriately, and they are prescribed frequently. Outside this supplement, no published DUE criteria for parenteral fluoroquinolones currently exist. Suggested criteria include use in patients who would otherwise be candidates for oral fluoroquinolone therapy (for which published criteria exist) but who cannot use the oral route of administration due to gastrointestinal conditions predisposing to malabsorption or unavailability of the oral route; for severe infections due to gram‐negative pathogens; as a replacement for aminoglycosides when ototoxicity or nephrotoxicity is a substantial risk; targeting to resistant pathogens (i.e., not as empiric therapy); and targeting to therapeutic use only (not for prophylaxis). The DUE process is crucial for ensuring safe, effective, appropriate, and economical drug therapy. It is an effective mechanism for evaluating the use of new agents and as an educational tool for clinicians in the postmarketing period.
The Role of Helicobacter pylori in Peptic Ulcer Disease
Authors: Partipilo Maria L. , Woster Patricia S.
Published: October 2023

The pathophysiology of peptic ulcer disease (PUD) is often described as an imbalance between aggressive factors such as acid and pepsin and alterations in the mucosal protective mechanisms. Helicobacter pylori is a gram‐negative organism that has been identified as a potential causative agent in the pathogenesis of PUD. The exact mechanism by which it contributes to mucosal damage is unknown. It is thought that the organism may disrupt the protective mucous layer, allowing the underlying epithelium to be injured by gastric acid. Significant evidence indicates that H. pylori is a major etiologic factor in type B gastritis. Data confirming its etiologic role in duodenal ulcer (DU) disease is not conclusive; however, eradication of the organism is associated with a reduction in the recurrence of DU. Optimum therapy to eradicate H. pylori has not been established, although several multidrug regimens have been evaluated. Treatment of H. pylori infection should be reserved for individuals in whom conventional therapy for DU is unsuccessful and those whose ulcers relapse during maintenance therapy.
Liver Disorders in Patients Receiving Chlorpromazine or Isoniazid
Authors: Derby Laura E. , Gutthann Susanne Pérez , Jick Hershel , Dean Alan D.
Published: October 2023

Based on information derived from computers and clinical records obtained from general practitioners in the United Kingdom, we estimated the frequency of liver toxicity associated with two known hepatotoxins, chlorpromazine and isoniazid. Among the cohort of 10,502 users of chlorpromazine, 14 had illnesses compatible with drug‐induced liver disease, a frequency of 1.3/1000 users (95% CI 0.8, 2.2). Four presumed cases of the disorder occurred among 921 users of isoniazid, for a frequency of 4/1000 users (95% CI 1.7, 11.1). This study provides population‐based quantification of the frequency of liver disorders associated with the use of these two agents.
Pharmaco‐legal Considerations in the Clinical Use of Decongestants
Authors: Brushwood David B.
Published: October 2023

Thanks to changes in the health care environment, pharmacists are no longer viewed as merely dispensers of pharmaceuticals. They are now required to render judgments concerning patient therapy based on legal mandates directed at accuracy, efficiency, and quality of care. Moreover, pharmacists' decisions and actions are governed by legal requirements for patient counseling, drug therapy monitoring, and drug substitution. A number of these requirements stem from the federal Omnibus Budget Reconciliation Act of 1990 legislation relating to Medicaid, which mandates expanded responsibilities for pharmacists. For the past decade, however, state regulations have governed risk‐assessment and risk‐management responsibilities with regard to physicians and pharmacists. The original antisubstitution laws, which were exceptionally restrictive, have been replaced by newer regulations clearly defining pharmacists' legal responsibilities regarding drug substitution. These regulations address patient consent, cost savings, Orange Book standards, and delayed‐release dosage forms. All of them have considerable impact on the dispensing of decongestants by pharmacists.
The Use of Angiotensin‐Converting Enzyme Inhibitors After Acute Myocardial Infarction
Authors: Mehra Iia V. , Wilson Marcus D.
Published: October 2023

During and immediately after myocardial infarction (MI), many interrelated and complex processes manifest the body's attempt to minimize damage and compensate for lost cardiac function. Although these compensatory responses may provide some short‐term restoration of function, their long‐term consequences actually may increase morbidity and mortality. Several agents have established roles in the treatment of these patients, whereas others, including the angiotensin‐converting enzyme (ACE) inhibitors, have yet to be investigated thoroughly. Results of two trials investigating the role of ACE inhibition after MI seem to provide sufficient data to warrant the use of these drugs in certain patient populations. These results are promising, but further investigation is necessary to answer key questions arising from these trials.
Prevention of Auditory Sequelae in Pediatric Bacterial Meningitis: A Meta‐Analysis
Authors: Yurkowski Peter J. , Plaisance Karen I.
Published: October 2023

Meta‐analysis methods were used to compare the effect of antibiotic regimens and corticosteroids on the development of auditory sequelae after pediatric bacterial meningitis. After a literature search of two major data bases, 11 studies met the criteria and were included in the analysis. Summary odds ratios, with 95% confidence intervals, were calculated that quantified the relative risk of developing auditory sequelae after specific therapies. No significant differences among antibiotics were identified in terms of reducing the risk of meningitis‐related hearing impairment. However, corticosteroids significantly reduced the frequency of bilateral, moderate, or greater hearing loss. Patients receiving placebo versus dexamethasone were much more likely to develop auditory dysfunction (odds ratio 3.77; 95% CI 1.77‐8.10). The results of this study add quantitative evidence supporting the use of dexamethasone as adjunctive therapy in pediatric bacterial meningitis.
Fetal Exposure to Lisinopril: Neonatal Manifestations and Management
Authors: Bhatt‐Mehta Varsha , Deluga Karl S.
Published: October 2023

The use of angiotensin‐converting enzyme (ACE) inhibitors in pregnancy has been associated with neonatal morbidity and mortality. The mechanism of renal dysfunction likely is related to fetal hypotension and prolonged decreased glomerular filtration. Six of 14 previously published cases of neonatal renal failure after maternal ACE inhibitor therapy resulted in death. Eight infants survived after peritoneal dialysis, some with residual renal impairment. Serum lisinopril levels and ACE activity in our patient indicate that during the anuric state the drug has an extremely prolonged half‐life, and that it is removed by peritoneal dialysis. In view of this prolonged half‐life and the drug's continued suppression of ACE activity and renal function, we recommend institution of early dialysis in infants with renal failure after maternal therapy with lisinopril.
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.
Intranasal l‐threo‐3,4,‐dihydroxyphenylserine in Treating Diarrhea Associated With Familial Amyloidotic Polyneuropathy
Authors: Ando Yukio , Gotoh Toshiomi , Kawaguchi Yutaka , Tanaka Yoshiya , Sakashita Naomi , Ando Masayuki
Published: October 2023

We evaluated the absorption disturbance of the gastrointestinal tract in patients with familial amyloidotic polyneuropathy (FAP). Ursodeoxycholic acid (UDCA) 300 mg was administered orally to 10 patients with FAP and 11 control subjects. Serum levels of total bile acid were determined as an indicator of absorption. The patients had lower serum levels of total bile acid than controls, suggesting an absorption disorder. To attempt to treat the diarrhea commonly associated with FAP, l‐threo‐3,4‐dihydroxyphenylserine (l‐threo‐DOPS), a synthetic precursor of norepinephrine, was administered 100 mg/dose by the oral and 8 mg/0.4 ml by the intranasal route and their effects on the elevation of serum norepinephrine levels were compared. The 3–0‐monohemiphthalate salt of glycyrrhizinic acid and sodium ascorbate were used as vehicles for the intranasal preparation to enhance drug absorption and prevent oxidation. Increased serum levels of norepinephrine, the converted metabolite of l‐threo‐DOPS in serum, was observed 2 hours after intranasal administration, but not after administration of the oral preparation or vehicle alone. Intranasal administration of 8 mg 3 times/day for 1 week resulted in reduction of the daily frequency of diarrhea as well as a decrease in the severe orthostatic hypotension in three patients with FAP. Thus, an intranasal delivery system for l‐threo‐DOPS, which acts by stimulating adrenergic receptors, may be considered in treating patients with FAP with severe diarrhea.
The Nuclear Status of Human Sperm Cells by TEM Image Cytometry: Nuclear Shape and Chromatin Texture in Semen Samples from Fertile and Infertile Men
Authors: AUGER J. , SCHOEVAERT D. , NEGULESCO I. , DADOUNE JP.
Published: October 2023

ABSTRACT Changes in nuclear size, shape, and chromatin texture during spermiogenesis and epididymal transport of human sperm were recently analyzed using transmission electron microscopy (TEM) image cytometry followed by multivariate statistical analysis of data. In the present study, this same methodology was used to investigate the nuclear morphology of spermatozoa in semen samples from fertile and infertile men. Analysis was carried out on a large series of micrographs of sections of sperm nuclei from a donor group with proven fertility and from a patient group with a mean infertility duration of 10 years with no obvious male or female infertility factors (only a slight decrease in the proportion of sperm heads with normal morphology was noted in routine semen tests). For the patient group, it was found that nuclei had a significantly less flattened shape (i.e., increased roundness as a consequence of increased thickness and decreased length). Furthermore, significant differences between donor and patient groups were found for most parameters of chromatin texture. In the patient group, chromatin was less condensed, and there was more homogeneous distribution of the different degrees of chromatin condensation. In addition, the organization of chromatin condensation and distribution along the major axis of the nucleus was found to be significantly different in the two groups. Stepwise linear discriminant analysis indicated a good classification rate of only 66% for nuclel of patients when using the eight major nuclear parameters, thus indicating the striking heterogeneity of nuclear morphology for both patient and donor groups. However, parameter ranking showed the predominant discriminatory capacity of chromatin texture parameters compared to size and shape parameters, thus reinforcing the need for including tests for evaluating the nuclear status of sperm cells in routine semen analysis.
Effect of Spermatocele Fluid on Growth of Human Prostatic Cells in Culture
Authors: SUTKOWSKI DEBRA M. , KASJANSKI RICHARD Z. , SENSIBAR JULIA A. , NEY KENNETH G. , LIM DAVID J. , KOZLOWSKI JAMES M. , LEE CHUNG , GRAYHACK JOHN T.
Published: October 2023

ABSTRACT: The present study was carried out to investigate whether testicular fluid derived from a spermatocele contains substance(s) that promote the growth of human prostatic cells in culture. Human spermatocele fluid was centrifuged to sediment spermatozoa. The supernatant was then added to cultures of human prostatic stromal or epithelial cells that were isolated from surgical specimens of benign prostatic hyperplasia. Addition of spermatocele fluid in quantities of 1 μg/ml of protein resulted in a significant increase in the number of both prostatic stromal and epithelial cells at the end of a 6‐day culture period. Human serum at equivalent protein concentrations in the culture medium had no stimulatory effect. At least two separate growth‐promoting factors were found in spermatocele fluid, one for stromal cells and one for epithelial cells. The mitogen for stromal cells was heat labile and persisted after treatment with activated charcoal. The factor for epithelial cells was heat stable but was removed by charcoal treatment. These observations are consistent with the concept that the human testis secretes nonandrogenic substances that can promote prostatic growth.
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

Immunohistochemical (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

The 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

The 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

Bursa 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

The 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

Critically 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

This 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.

Purpose

We 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 Type

Retrospective.

Subjects

The 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/Sequence

Seven 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.

Assessment

An 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.

Results

Our 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.

Conclusion

This study presents a DL strategy to mitigate batch effects in diffusion MR images, improving their quality and generalizability.

Evidence Level

3

Technical Efficacy

Stage 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

Chronic 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

Problem‐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.