bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Simultaneous Didanosine Administration on Itraconazole Absorption in Healthy Volunteers
Authors: May D. Byron , Drew Richard H. , Yedinak Kimberly C. , Bartlett John A.
Published: October 2023

Study Objective. To investigate the effect of simultaneously administered didanosine (ddI) on the absorption of a single dose of itraconazole.

Design. Randomized, crossover, unblinded single‐dose pharmacokinetic study in healthy volunteers. Comparisons of itraconazole alone and itraconazole with simultaneous ddI were performed on days 1 and 15.

Setting. A university medical center.

Patients. Seven healthy men and women. Six subjects (86%) completed the study; one was removed due to the development of a rash.

Interventions. Volunteers received a single 200‐mg oral dose of itraconazole or itraconazole with concomitant oral ddI 300 mg (two 150‐mg tablets) dispersed in 240 ml water. Each regimen was separated by a 2‐week washout period. Serum samples were obtained frequently for 12 hours after the dose.

Measurements and Main Results. Concentrations of itraconazole were determined using a microbiologic assay. Individual concentrations in serum versus time data were evaluated by linear regression analysis. Peak serum concentration and time to peak were determined by visual inspection of each individual's serum concentration‐time curve. A mean ± SD peak serum itraconazole concentration of 0.90 ± 0.30 μg/ml was observed at 3.0 ± 0.7 hours when itraconazole was administered alone, compared with undetectable levels in all patients during therapy with ddI.

Conclusions. Simultaneous oral administration of ddI significantly decreases absorption of itraconazole. These drugs should not be administered concurrently.
Effect of Intravenous Fructose‐1,6‐Diphosphate on Myocardial Contractility in Patients With Left Ventricular Dysfunction
Authors: Munger Mark A. , Botti Robert E. , Grinblatt Michael A. , Kasmer Richard J.
Published: October 2023

Study Objective. To examine the effects of fructose‐1,6‐diphosphate on myocardial performance using nuclear scintigraphy.

Design. Prospective, randomized, single‐blind, parallel study.

Setting. Urban teaching hospital clinical research center.

Patients. Individuals with New York Heart Association functional class II—III heart failure (mild to moderate).

Interventions. Subjects received either intravenous fructose‐1,6‐diphosphate 125 mg/kg or normal saline 1.3 ml/kg every 12 hours over 10 minutes for four consecutive doses. Left ventricular performance was assessed by radionuclide ventriculography at baseline and within 60 minutes after the fourth infusion. Vital signs were monitored throughout the study period.

Measurements and Main Results. Fructose‐1,6‐diphosphate resulted in a modest 7% increase in left ventricular ejection fraction (p<0.05). Peak ejection rate and peak diastolic filling rate did not change significantly. There were no changes in blood pressure or heart rate with either fructose‐1,6‐diphosphate or placebo.

Conclusions. Fructose‐1,6‐diphosphate produces a modest but significant increase in left ventricular ejection fraction in patients with mild to moderate heart failure.
Genital Herpes Simplex Infections in Patients With the Acquired Immunodeficiency Syndrome
Authors: McGrath Betty J. , Newman Cheryl L.
Published: October 2023

On August 14, 1987, the Centers for Disease Control revised the surveillance case definition for the acquired immunodeficiency syndrome (AIDS) to include several indicator diseases. The addition of herpes simplex virus (HSV) infections to the definition reemphasized the increasing frequency of severe HSV infections in patients also infected with the human immunodeficiency virus (HIV). These infections in patients with AIDS are associated with considerable morbidity similar to reports of HSV in other immunocompromised populations. Their spectrum can include persistent or recurrent genital disease, severe visceral involvement, and disseminated infection. Patients with AIDS also are at increased risk of drug toxicities when receiving treatment for HSV infections in addition to antiretroviral therapy. Acyclovir, a selective and specific inhibitor of HSV replication, has been the mainstay of safe and effective treatment for HSV for more than a decade. However, reports of acyclovir‐resistant strains of HSV in patients with AIDS have been steadily increasing since 1989. Although foscarnet has been successful in treating acyclovir‐resistant strains, foscarnet‐resistant strains have also been isolated. The search to find novel approaches for the treatment and suppression of HSV in patients with AIDS has become an added challenge in the management of this devastating disease.
Predictors of Future Antihypertensive Use in Patients With Mildly Elevated Blood Pressure
Authors: Barbour Marilyn McFarland , Hume Anne Lamont , Lapane Kate L. , Derby Carol A. , Carleton Richard A.
Published: October 2023

We prospectively identified predictors of future antihypertensive use in untreated persons age 18–65 years who had elevated diastolic blood pressures of 90–104 mm Hg or systolic blood pressures of at least 140 mm Hg. Data were derived from two independent cohorts completing household surveys conducted in 1981–1984 and 8 years later, as part of the Pawtucket Heart Health Program. Demographics, self‐reported health behaviors and beliefs, and physiologic measurements were obtained. Drug use was determined through structured interviews. Analysis of covariance and logistic regression were performed. In the 492 subjects, independent baseline predictors of future antihypertensive use (p<0.05) included female gender, older age, diastolic blood pressure elevation, self‐perceived high blood pressure, and self‐reported salt limitation. Antihypertensive use for previously untreated mild hypertension is diverse. Older women with diastolic elevations who are health conscious are most likely to be treated.
Effects of Carbamazepine on Cyclosporine Metabolism in Pediatric Renal Transplant Recipients
Authors: Cooney Gerard F. , Mochon Manuel , Kaiser Bruce , Dunn Stephen P. , Goldsmith Barbara
Published: October 2023

This study documents a pharmacokinetic interaction between carbamazepine and cyclosporine (CsA) in pediatric renal transplant recipients. Noncompartmental steady‐state CsA pharmacokinetics were determined in three pediatric renal transplant recipients who were receiving both CsA and carbamazepine as long‐term therapy (carbamazepine group) and in three matched renal transplant subjects who were not receiving carbamazepine (control group). Even though the mean daily dosage of CsA was consistently higher in the carbamazepine group than in the control group (16.2 mg/kg/24 hrs vs 10.8 mg/kg/24 hrs, respectively), the predose trough CsA blood concentrations were significantly lower in the carbamazepine group (57 ng/ml vs 162 ng/ml, respectively; p=0.0023). Mean average steady‐state blood concentrations of CsA (Cav) per mg of CsA administered were less than 50% in the carbamazepine group compared with the control group. This reflects either an induction of CsA hepatic metabolism or a reduced systemic bioavailability (possible induction of pre‐hepatic metabolism) by concurrent use of carbamazepine.
Platelet‐Activating Factor Acetylhydrolase Activity in Bovine Seminal Plasma
Authors: PARKS JOHN E. , HOUGH SHELLEY R.
Published: October 2023

Platelet‐activating factor (PAF) is a potent signaling molecule that has been detected in mammalian sperm from several species. The biological function of sperm‐derived PAF and mechanisms controlling its production have not been clearly defined. In the remodeling pathway for PAF biosynthesis, PAF is produced by phos‐pholipase A2 hydrolysis of 1‐O‐alkyl phospholipids followed by acetylation by PAF acetyltransferase. PAF is inactivated by PAF acetylhydrolase. PAF acetylhydrolase activity has been detected recently in human seminal plasma, where it may play a role in regulating PAF production or content by sperm. The purpose of this study was to measure and partially characterize PAF acetylhydrolase in bovine seminal plasma. Acetylhydrolase activity was detected in seminal plasma, was linear with time and protein concentration, and had a specific activity of 122 nmol/minute/mg protein. The enzyme was cation independent and was not inhibited by phosphatidylcholine but was inhibited by p‐bromophenacylbromide and partially inhibited by phenylmethylsulfonylfluoride. Very little acetylhydrolase activity was detected in caudal epididymal fluid or caudal epididymal sperm. Enzyme activity associated with ejaculated sperm was largely removed by their centrifugation through Percoll and subsequent washing. These results demonstrate very high PAF acetylhydrolase activity in bovine seminal plasma. The enzyme appears to be of accessory gland origin and has properties similar to those of the enzyme from other sources.
The Effect of Aging on the Seminiferous Epithelium of the Brown Norway Rat
Authors: WRIGHT WILLIAM W. , FIORE CARA , ZIRKIN BARRY R.
Published: October 2023

ABSTRACT:Aging of the mammalian testis is often accompanied by loss of germ cells and, as a result, decreased daily sperm production. It is currently unknown whether cell loss is the result of aging‐related changes in germ cells or whether there are also aging‐related changes in the Sertoli cells that normally support germ development and differentiation. To begin to compare the effects of age on germ cells and on Sertoli cells, we examined brown Norway rats of 6, 12, 18, 21, and 24 months of age for the frequency of seminiferous tubule regression and total testis contents of transcripts for three Sertoli cell products: SGP‐2, transferrin, and cyclic protein‐2 (CP‐2)/cathepsin L. Histological analysis revealed no changes in the seminiferous epithelium from 6 to 12 months of age. However, from 12 to 24 months of age, the percentage of normal tubules gradually decreased from 95% to 15% of the total while the percentage of fully regressed tubules (containing no germ cells per tubule cross section) increased from 0% to 78%. In our analysis of specific Sertoli cell transcripts, we noted no change in total testis content of SGP‐2 mRNA from 6 to 24 months. However, total testis content of transferrin mRNA was unchanged from 6 to 18 months, but increased by 24 months to 368% of the content of a 6‐month‐old testis. In contrast, total testis content of CP‐2/cathepsin L mRNA was unchanged from 6 to 12 months, but decreased by 24 months to 58% of the content of a 6‐month‐old testis. We conclude that aging‐related loss of spermatogenic cells in the brown Norway rat is accompanied by specific changes in expression of particular Sertoli cell transcripts.
Neonatal Goitrogen Treatment Increases Adult Testis Size and Sperm Production in the Mouse
Authors: JOYCE KIMBERLY L. , PORCELLI JOHN , COOKE PAUL S.
Published: October 2023

ABSTRACT Male rats made hypothyroid during neonatal life show unprecedented increases in adult testis size and daily sperm production (DSP). To determine if this effect was unique to the rat or could also be demonstrated in other species, we examined the effects of neonatal treatment with the reversible goitrogen 6‐propyl‐2‐thiouracil (PTU) on adult testis size and function in the mouse. Male Swiss‐Webster mice were untreated (control) or given PTU by adding 0.1% (w/v) to their mother's water from birth to day 25 postpartum. All pups were then weaned and given no further treatment. Sertoli cell proliferation was examined using tritiated thymidine autoradiography in some control and treated mice at 0, 5, 10, 15, 20, and 25 days, while the remainder were killed at 90 days to determine a variety of reproductive parameters. Neonatal PTU treatment decreased growth; body weight of treated mice at 4 weeks of age was 57% less than controls. Treated mice grew rapidly following cessation of PTU treatment, although their weights never equalled controls, remaining 17% smaller at 90 days of age. At 90 days of age, testis weight and DSP were increased by approximately 30% and 50%, respectively, in PTU‐treated mice compared to controls. Despite the increased testis weight and function, serum testosterone concentrations were not different in control and treated mice. Testicular and epididymal histology in treated mice was similar to controls, while epididymal sperm in treated mice were motile and morphologically normal. Sertoli cell proliferation was altered in treated mice. The normal decrease in proliferative rate seen during early postnatal life was slowed, and by day 10 postnatal, the labeling index of treated Sertoli cells was about fourfold greater than that of controls. Furthermore, Sertoli cells in treated mice proliferated until day 25, whereas proliferation ceased in controls by day 15. In summary, neonatal PTU treatment increases testis weight, DSP, and the efficiency of sperm production (DSP/g testis) in the mouse, indicating that the PTU effect on testis development clearly occurs in other species. Furthermore, increased Sertoli cell proliferation appears to be the critical event for the development of this phenomenon in mice, as it is in rats. The existence of unique mutations that affect testicular development make the mouse an advantageous model for determining the mechanism of this effect. This technique may also be useful for increasing testicular size, sperm production, and fertility in various mutant mouse strains and transgenic mice in which these parameters are reduced.
Studies on Sperm Chromatin Structure Alterations and Cytogenetic Damage of Mouse Sperm Following In Vitro Incubation. Studies on In Vitro‐Incubated Mouse Sperm
Authors: ESTOP A. M. , MUNNÉ S. , JOST L. K. , EVENSON D. P.
Published: October 2023

ABSTRACT: Mouse epididymal sperm incubated in Tyrode's T6 fertilization media were analyzed over time for chromosome damage by two methods. First, cytogenetic analysis was done on paternal pronuclei metaphase chromosomes. After 6 hours incubation 11% of the cells demonstrated chromosome structural abnormalities. Secondly, sperm nuclei were measured by the sperm chromatin structure assay, which is a measure of the susceptibility of sperm DNA to the nuclei demonstrated an increased susceptibility to DNA denaturation, reaching near 100% by 48 hours. Changes in chromatin structure at the molecular level may lead to chromosome breaks seen in pronuclear chromosomes.
Seminal Tract Washout: A New Diagnostic Tool in Complicated Cases of Male Infertility
Authors: COLPI GIOVANNI M. , NEGRI LUCIANO , SCROPPO FABRIZIO I. , GRUGNETTI CRISTINA , PATRIZIO PASQUALE
Published: October 2023

ABSTRACT: The diagnosis of azoospermia or severe oligospermia that is made using conventional techniques (testicular biopsy, epididymal exploration, and vasovesiculography) may in some cases remain a dilemma. In such circumstances, post‐testicular causes of obstruction must be evaluated. Following the clinical experience acquired in a selected population of 150 severely infertile subjects, the total sperm count in the fluid obtained from the bladder after a seminal tract washout during vasovesiculography has proved to be a valid tool to diagnose the location of the (sub‐)obstruction in the seminal tract in complicated cases.

Some representative cases are presented. In particular, seminal tract washout (STW) helps to identify functional distal seminal tract emptying disturbances and epididymal incomplete obstruction.
Hematospermia
Authors: Papp György K. , Hoznek Andras , Hegedüs Magdolna , Juhasz Endre
Published: October 2023

ABSTRACT: The appearance of blood in the seminal fluid is an alarming sign, with a rather inconstant origin. The causes of hematospermia are discussed based on a review of the literature and the authors' own experience with 84 patients. The importance of differential diagnosis is emphasized and a diagnostic scheme is presented. Therapeutic opportunities depending on etiology are discussed. It is concluded that although hematospermia is an often self‐limiting sign, resolving in a few weeks, all patients should undergo a careful investigation to rule out the presence of malignancy or other significant disease.
Transurethral Endoscopic Treatment of Distal Seminal Tract Obstruction
Authors: RUIZ‐CASTAÑÉ E. , VICENTE J.
Published: October 2023

ABSTRACT: The two distal obstructive pathologies of the seminal duct found at our center are ejaculatory duct obstruction and utriculocele. Between 1979 and 1993, we present a total of 22 cases, 13 cases of ejaculatory duct obstruction and nine of utriculocele. The usual manifestations include infertility, ejaculatory discomfort, testicular pain, perineal discomfort, and hematospermia. Also, symptoms of urinary obstruction and repeated urinary infections can be present.

The preparatory evaluation studies are many and varied. Excellent images are obtained with transrectal echography. In cases associated with infertility, very low seminal volume is recorded (1 ml or less) with azoospermia or oligospermia. The semen fructose is either very low or absent altogether. The serum FSH is normal. The testicular biopsy is indicative of the conservation of the spermatogenesis. It is also of prime importance to check that there is no epididymal tubular rupture caused by increased pressure or by epididymitis because a combination of endoscopic surgery with epididymovasostomy would then be necessary. Seminal vesiculography indicates the level of obstruction.

A high scrotal incision was made over the vas deferens and the vas cannulated with a 24‐gauge intravenous catheter into which methylene blue was injected while the prostatic urethra was monitored under direct vision endoscopically (chromo‐ejaculoscopy). Endoscopic resection was accomplished and appearance of the blue dye could be used as a measure of adequate resection.

An improvement in semen volume was observed in 14 patients, and in two patients pregnancies were obtained by means of assisted reproduction techniques. There were no serious complications in any of the cases; only two patients suffered postsurgical epididymitis.
A unified DNA‐ and RNA‐based NGS strategy for the analysis of multiple types of variants at the dual nucleic acid level in solid tumors
Authors: Chen Huijuan , Wang Bing , Zhang Yiran , Shu Yingshuang , Dong Henan , Zhao Qian , Yang Chunyan , Li Jianji , Duan Xiaohong , Zhou Qiming
Published: October 2023

Background

Targeted next‐generation sequencing (NGS) is a powerful and suitable approach to comprehensively identify multiple types of variants in tumors. RNA‐based NGS is increasingly playing an important role in precision oncology. Both parallel and sequential DNA‐ and RNA‐based approaches are expensive, burdensome, and have long turnaround times, which can be impractical in clinical practice. A streamlined, unified DNA‐ and RNA‐based NGS approach is urgently needed in clinical practice.

Methods

A DNA/RNA co‐hybrid capture sequencing (DRCC‐Seq) approach was designed to capture pre‐capture DNA and RNA libraries in a single tube and convert them into one NGS library. The performance of the DRCC‐Seq approach was evaluated by a panel of reference standards and clinical samples.

Results

The average depth, DNA data ratio, capture ratio, and target coverage 250 (×) of the DNA panel data had a negative correlation with an increase in the proportion of RNA probes. The SNVs, indels, fusions, and MSI status were not affected by the proportion of RNA probes, but the copy numbers of the target genes were higher than expected in the standard materials, and many unexpected gene amplifications were found using D:R (1:2) and D:R (1:4) probe panels. The optimal ratio of DNA and RNA probes in the combined probe panel was 1:1 using the DRCC‐Seq approach. The DRCC‐Seq approach was feasible and reliable for detecting multiple types of variants in reference standards and real‐world clinical samples.

Conclusions

The DRCC‐Seq approach is more cost‐effective, with a shorter turnaround time and lower labor requirements than either parallel or sequential targeted DNA NGS and RNA NGS. It is feasible to identify multiple genetic variations at the DNA and RNA levels simultaneously in clinical practice.
Dose–response effects of resistance training on physical function in frail older Chinese adults: A randomized controlled trial
Authors: Lai Xiaoxing , Zhu Hongwei , Wu Zhao , Chen Baoyu , Jiang Qian , Du Hongdi , Huo Xiaopeng
Published: October 2023

Background

Effective exercise for the frail elderly has been found to contribute to healthy aging; the corresponding relationship between intensity and volume of exercise and health effects remains unclear. The present study aimed to investigate the dose–response effects of resistance training on muscle strength and physical fitness in frail older adults.

Methods

In this randomized controlled trial, participants were randomized into seven groups: moderate‐volume low‐intensity, moderate‐volume moderate‐intensity, moderate‐volume high‐intensity, high‐volume low‐intensity, high‐volume moderate‐intensity, high‐volume high‐intensity and routine care, receiving 12 weeks of resistance training of different intensities and volumes of exercise. The outcomes were muscle strength (assessed by ergonomics force gauges) and physical fitness function (assessed by the 6‐min walking test [6MWT], the 30‐s sit‐to‐stand test [30sSTST] and the 8‐foot up‐and‐go test [8‐FUGT]) before and at 6 and 12 weeks of intervention.

Results

A total of 161 participants completed the exercise intervention. There were no significant differences in age, sex, height, body weight and body mass index among the seven groups. The exercise volume of resistance training showed linear relationships with muscle strength of the lower limbs, 30sSTST and 6MWT results and a non‐linear relationship with 8‐FUGT. Resistance training intensity was found to have a linear relationship with muscle strength of the lower limbs and 6MWT and non‐linear relationships with 30sSTST and 8‐FUGT. The mixed linear model analysis revealed that the lower limb muscle strength differed significantly before and during the intervention (W = 8571.5, Padj < 0.001), before and after the intervention (W = 6968, Padj = 0.001) and during and after the intervention (W = 2834.5, Padj < 0.001); that the 6MWT performance differed during and after the intervention (W = 3184, Padj < 0.001); and that the 30sSTST was different between before and during the intervention (W = 2350.5, Padj = 0.012) and between during and after the intervention (W = 2290.5, Padj = 0.045).

Conclusions

Resistance training was found to be associated with muscle strength and physical fitness in frail older adults in a dose‐dependent manner. High‐intensity resistance training could be more effective for improving the muscle strength of frail older adults, and the improvement of 6MWT performance was even higher. High‐volume resistance training significantly improved muscle strength, with even greater improvement in the 30sSTST and 6MWT performances. Both the intensity and volume of exercise were found to greatly value physical function in frail older adults. Low–moderate‐intensity resistance training and low–moderate‐volume resistance training also had some advantages in terms of safety, efficacy and acceptance in elderly with frailty.
Exploring and describing current behavioral and social sciences curricula in predoctoral dental programs
Authors: Wright Casey D. , Young Lance Brendan
Published: October 2023

Purpose

To maintain accreditation status, predoctoral dental programs in the United States and Canada are required to train future dentists in the fundamentals of behavioral sciences. Each program independently determines how to fulfill this task, and little information exists on the consistency of training across programs. The purpose of this study was to identify the range of topics currently taught in predoctoral dental programs in the United States and Canada, who teaches them, and the modes of instruction and assessment.

Methods

Invitations to complete an online survey were emailed to faculty responsible for, or familiar with, the behavioral sciences curricula at 75 predoctoral dental programs in the United States and Canada. Questions elicited information on behavioral sciences education at each program, including instructor background, topics taught, instructional and assessment methods, and sources of content.

Results

Of those invited, 27 (36%) completed surveys. Per the responses, prototypical behavioral sciences programs usually consist of didactic/lecture format teaching, mostly during the first 2 years of the predoctoral program, by a dentist who assesses students using multiple‐choice or true/false exams. The results indicated, however, substantial variation in what is taught, how it is taught, who teaches it, and how it is assessed.

Conclusions

While being a requirement for accreditation, this study demonstrated how behavioral and social sciences topics, teaching strategies, and assessments, along with the individuals teaching those topics varied across predoctoral programs. Consistency, coordination, and clinical integration are possible ways of enhancing behavioral science instruction.
Benefit of lymph node dissection for perihilar and distal cholangiocarcinoma according to lymph node stations
Authors: Terasaki Fumihiro , Sugiura Teiichi , Okamura Yukiyasu , Ashida Ryo , Ohgi Katsuhisa , Yamada Mihoko , Ohtsuka Shimpei , Uesaka Katsuhiko
Published: October 2023

Background

The benefits of lymph node (LN) dissection at each station have not previously been fully investigated in perihilar cholangiocarcinoma (PHCC) and distal cholangiocarcinoma (DCC).

Methods

The efficacy index (EI) was calculated in patients who underwent surgery for PHCC (n = 134) and DCC (n = 135) by multiplying the frequency of metastasis to the LN station and the 5‐year overall survival (OS) rate of patients with metastasis to that station.

Results

In PHCC, the frequency of metastasis, 5‐year OS rates, and the EI in para‐aortic LNs (4.7%, 0%, and 0, respectively) and posterior pancreaticoduodenal LNs (8.1%, 0%, and 0, respectively) were lower than those in hepatoduodenal ligament LNs (30.1%, 24.1%, and 7.25, respectively) and LNs along the common hepatic artery (CHA) (16.2%, 15.0%, and 2.43, respectively). In DCC, these values were lower in LNs along the CHA (6.4%, 0%, and 0, respectively) than in the posterior pancreaticoduodenal LNs (31.2%, 34.5%, and 10.8, respectively), the hepatoduodenal ligament LNs (14.8%, 15.2%, and 2.25, respectively), and para‐aortic (4.0%, 25.0%, and 0.99, respectively) LNs.

Conclusions

According to the EI, this study raises concerns about the effectiveness of dissection in the posterior pancreaticoduodenal LNs in PHCC and LNs along the CHA in DCC.
Effectiveness of a career intervention for improving career‐related outcomes in higher education students with disabilities
Authors: Ip Priscilla Sei Yah , Hui Anna Na Na
Published: October 2023

Young people with disabilities (YPWDs) in higher education require tailored career support in finding employment. Seventy‐five YPWDs in Hong Kong participated in a quantitative program effectiveness study using a three‐group comparison design (experimental, other intern, and control) to improve career‐related outcomes. Generalized estimating equations revealed that the experimental group showed significant improvements in career‐related outcomes such as career decision self‐efficacy and focused job search strategy while increasing disability‐related outcomes and work cynicism. This study reveals the impact of disability on work experience and its benefits for YPWDs. Important policy implications for future school–work transition programs for YPWDs are discussed.
Dimer acid used as CO2‐responsive surfactant for reducing viscosity of heavy crude oil
Authors: He Xiran , Luan Huoxin , Guan Dan , Zhang Mingmin , Li Zhengyang , Su Xin , Wu Yuanpeng
Published: October 2023

The efficacy of CO2‐switchable surfactants in reducing viscosity of heavy crude oil has received widespread attention due to its switchable surface activity for constructing reversible emulsion. However, the intricate synthesis processes of these surfactants pose a significant challenge in their practical application. The present investigation involved the preparation of surfactants that are responsive to CO2, specifically dimer acid (DA)/tetramethylpropylenediamine (TMPDA), through a facile mixing approach. These surfactants were subsequently employed to mitigate the high viscosity of heavy crude oil. The study employed a surface tension meter to examine the surface behavior of DA/TMPDA, which demonstrated the potential for reducing viscosity. The study examined the CO2 responsiveness of DA/TMPDA through the application of alternating CO2 and N2. It confirmed the reversible CO2 responsiveness of the surface activator. The results from the emulsification and viscosity reduction assessments suggest that the amalgamation of DA and TMPDA in a 1:1 molar ratio yielded a surfactant. This surfactant demonstrated favorable stability in water and heavy crude oil emulsions, as well as low viscosity and rapid emulsion breaking upon exposure to CO2. This investigation demonstrates that it is feasible to produce surfactants that are responsive to CO2 and possess the ability to reduce viscosity through a straightforward mixing process. This presents a viable approach to utilizing oligomeric surfactants that are CO2‐responsive for the purposes of emulsifying and breaking down heavy crude oil.
The Value of Percutaneous Contrast‐Enhanced Ultrasound in Sentinel Lymph Node Identification, Metastatic Status and Burden Diagnosis in Early Breast Cancer
Authors: Pang Wenjing , Zhou Fei , Zhu Yangyang , Jia Yingying , Nie Fang
Published: October 2023

Objective

The aim of this study was to evaluate the value of percutaneous contrast‐enhanced ultrasound (PCEUS) in the identification and characterization of sentinel lymph node (SLN).

Methods

A total of 102 breast cancer patients were collected and underwent preoperative PCEUS, which was used to identify SLN and lymphatic drainage. SLNs were classified into 4 enhancement patterns, including 6 subtypes: homogeneous (I), featured inhomogeneous (II) including inhomogeneous hypoenhancement (IIa) and annular or semi‐annular enhancement (IIb), focal filling defect (III) including filling defect area < 50% (IIIa) and filling defect area ≥ 50% (IIIb), and no enhancement (IV). The enhancement patterns of SLNs were compared with the final pathological diagnosis.

Results

The identification rate of SLNs using PCEUS was 100% (102/102); the rate of identification of LCs was 100% (102/102), and the coincidence rate was 98.0% (100/102). Four lymphatic drainage patterns (LDPs) including 5 subtypes were found: single LC/single SLN(74.5%), multiple LCs/ single SLN (13.7%) including 2 subtypes:2 LCs/1 SLN and 3 LCs/1 SLN, single LC/multiple SLNs (7.8%), and multiple LCs/multiple SLNs (3.9%). A total of 86.3% (44/51) of patients without axillary metastasis could be safely selected for types I, IIa, and IIb, while the axillary metastasis rates of types III and IV were 74.4% and 87.5%, respectively (P < .001). Compared with grayscale US, the PCEUS significant improvement in diagnosing metastatic SLNs (.794 versus .579, P < .001). For the SLN metastatic burden, Types I, IIa, IIb, and IIIa had ≤2 SLNs metastases, with a pathological coincidence rate of (64/67, 95.5%), and types IIIb and IV had >2 SLNs metastases, with a pathological coincidence rate of (25/35, 71.4%) (P < .001). The AUC of PCEUS for the diagnosis of SLN metastatic status and burden was .794 and .879, respectively (P < .001).

Conclusion

PCEUS has a high identification rate for SLN and has good potential for diagnosing SLN metastatic status and burden by enhancement patterns.
ANXA1sp attenuates sepsis‐induced myocardial injury by promoting mitochondrial biosynthesis and inhibiting oxidative stress and autophagy via SIRT3 upregulation
Authors: Qin Song , Ren Ying‐Cong , Liu Jun‐Ya , Chen Wen‐Bo , Fu Bao , Zheng Jie , Fu Xiao‐Yun
Published: October 2023

Sepsis‐induced myocardial injury is one of the most difficult complications of sepsis in intensive care units. Annexin A1 (ANXA1) short peptide (ANXA1sp) protects organs during the perioperative period. However, the protective effect of ANXA1sp against sepsis‐induced myocardial injury remains unclear. We aimed to explore the protective effects and mechanisms of ANXA1sp against sepsis‐induced myocardial injury both in vitro and in vivo. Cellular and animal models of myocardial injury in sepsis were established with lipopolysaccharide. The cardiac function of mice was assessed by high‐frequency echocardiography. Elisa assay detected changes in inflammatory mediators and markers of myocardial injury. Western blotting detected autophagy and mitochondrial biosynthesis‐related proteins. Autophagic flux changes were observed by confocal microscopy, and autophagosomes were evaluated by TEM. ATP, SOD, ROS, and MDA levels were also detected.ANXA1sp pretreatment enhanced the 7‐day survival rate, improved cardiac function, and reduced TNF‐α, IL‐6, IL‐1β, CK‐MB, cTnI, and LDH levels. ANXA1sp significantly increased the expression of sirtuin‐3 (SIRT3), mitochondrial biosynthesis‐related proteins peroxisome proliferator‐activated receptor γ co‐activator 1α (PGC‐1α), and mitochondrial transcription factor A (TFAM). ANXA1sp increased mitochondrial membrane potential (△Ψm), ATP, and SOD, and decreased ROS, autophagy flux, the production of autophagosomes per unit area, and MDA levels. The protective effect of ANXA1sp decreased significantly after SIRT3 silencing in vitro and in vivo, indicating that the key factor in ANXA1sp's protective role is the upregulation of SIRT3. In summary, ANXA1sp attenuated sepsis‐induced myocardial injury by upregulating SIRT3 to promote mitochondrial biosynthesis and inhibit oxidative stress and autophagy.
Fabrication of Gentamicin Sulfate‐Loaded 3D‐Printed Polyvinyl Alcohol/Sodium Alginate/Gelatin‐Methacryloyl Hybrid Scaffolds for Skin Tissue Replacement
Authors: Izgordu Muhammet Sefa , Ayran Musa , Ulag Songul , Yildirim Ridvan , Bulut Berrak , Sahin Ali , Guncu Mehmet Mucahit , Aksu Burak , Gunduz Oguzhan
Published: October 2023

3D‐printed scaffolds can better mimic the function of human skin, both biologically and mechanically. Within the scope of this study, the effect of the addition of different amounts (10, 15, 20 mg) of gentamicin sulfate (GS) to a 10 mL solution of natural and synthetic polymers is investigated. Sodium alginate (SA), gelatin‐methacryloyl (GelMA), and polyvinyl alcohol (PVA) are chosen as bioactive materials. The surface morphology and pore structures are visualized by scanning electron microscopy (SEM). According to the results, it is observed that the pore sizes of all scaffolds are smaller than 270 µm, the lowest value (130 µm) is obtained in the scaffold loaded with 15 mg GS, and it also has the highest tensile strength value (12.5 ± 7.6 MPa). Similarly, it is observed that the tensile strength (9.7 ± 4.5 MPa) is high in scaffold loaded with 20 mg GS. The biocompatibility test is performed with fibroblast cells, and the results show that the scaffolds are biocompatible with cells. The antibacterial test is carried out against the S.aureous and E. coli and the results indicate that all GS‐loaded scaffolds demonstrate antibacterial activity.
Prenatal diagnosis and preimplantation genetics testing of 3M syndrome in a Chinese family with novel biallelic variants of CUL7
Authors: Wang Xueqian , He Yaqiong , Wang Xiaorong , Kong Xiangtian , Lin Yunying , Yao Yejie , Huang Yi
Published: October 2023

Background

3M syndrome is a rare autosomal recessive developmental disorder characterized by pre and postnatal growth deficiency, dysmorphic facial features, and normal intelligence. 3M syndrome should be suspected in a proband with a combination of characteristic or recognizable dysmorphic features. The diagnosis of 3M syndrome could be confirmed by identifying biallelic variants in CUL7, OBSL1, or CCDC8.

Methods

Whole‐exome sequencing (WES) was performed to identify genetic causes. Reverse‐transcription polymerase chain reaction (RT‐PCR) was performed to detect aberrant splicing events. Haplotypes were constructed using multiplex PCR and sequencing. Variants of the parental haplotype and target likely pathogenic variants were detected by PCR and Sanger sequencing from the embryos. Copy number variant (CNV) detection was performed by next‐generation sequencing.

Results

We present the case of a nonconsanguineous Chinese couple with one abnormal pregnancy, where the fetus showed 3M phenotypes of shortened long bones. WES identified two novel heterozygous mutations in CUL7: NM_014780.5:c.354del (p.Gln119ArgfsTer52) and NM_014780.5:c.1373‐15G>A. RT‐PCR from RNA of the mother's peripheral blood leucocytes showed that c.1373‐15G>A caused the insertion of a 13‐bp extra intron sequence and encoded the mutant p.Leu459ProfsTer25. Both variants were classified as likely pathogenic according to ACMG/AMP guidelines and Clinical Genome Resource specifications. During genetic counseling, the options of prenatal diagnosis through chorionic villus sampling or amniocentesis, adoption, sperm donation, and electing not to reproduce, as well as preimplantation genetic testing for monogenic disorders (PGT‐M), were discussed. The couple hopes to conceive a child of their own and refused to accept the 25% risk during the next pregnancy and opted for PGT‐M. They finally successfully delivered a healthy baby through PGT‐M.

Conclusion

This study expanded the mutation spectrum of CUL7, detected the aberrant splicing event of CUL7 via RT‐PCR, constructed the haplotype for PGT‐M, and demonstrated the successful delivery of a healthy baby using PGT‐M.
A novel de novo frameshift variant in the CHD2 gene related to intellectual and developmental disability, seizures and speech problems
Authors: Mir Atefeh , Song Yongjun , Lee Hane , Nadeali Zakiye , Tabatabaiefar Mohammad Amin
Published: October 2023

Background

The chromodomain helicase DNA‐binding protein 2 (CHD2) is a member of the ATP‐dependent chromatin remodelling family of proteins, which are critical for the assembly and regulation of chromatin. De novo variants and deletions in the CHD2 gene have been associated with childhood‐onset developmental and epileptic encephalopathies type 94 (DEE 94). This study reports a novel deleterious de novo heterozygous frameshift insertion variant in the CHD2 gene.

Methods

The causative variant was diagnosed using whole‐exome sequencing. Sanger sequencing and cosegregation analysis were applied to confirm the candidate variant. Multiple in silico analysis tools were employed to interpret the variant using the American College of Medical Genetics and Genomics and the Association for Molecular Pathology guidelines.

Results

A de novo deleterious variant, NM_001271.4:c.1570dup (NP_001262.3:p.Ser524PhefsTer30), in the CHD2 gene, was identified in a 16‐year‐old boy with an intellectual and developmental disability, seizures and speech problems. The de novo occurrence of the variant was confirmed by segregation analysis in the family.

Conclusion

The findings of this study expand the existing knowledge of variants of the CHD2 gene and provide a detailed phenotype associated with this gene. These data could have implications for genetic diagnosis and counselling in similar conditions. Moreover, this information could be useful for therapeutic purposes, including the proper administration of medication to control epilepsy.
3′‐Hydroxypterostilbene Potently Suppresses Tumor Growth via Inhibiting the Activation of the JAK2/STAT3 Pathway in Ovarian Clear Cell Carcinoma
Authors: Koh Yen‐Chun , Huang Wei‐Zhe , Nagabhushanam Kalyanam , Ho Chi‐Tang , Pan Min‐Hsiung
Published: October 2023

Scope

Ovarian clear cell carcinoma (OCCC) is a subtype of epithelial ovarian cancer (EOC) that is associated with higher interleukin‐6 (IL‐6) levels, and suppression of the Janus kinase 2/Signal transducer and activator of transription 3 (JAK2/STAT3) pathway may contribute to the suppression of this cancer. This study aims to compare the anti‐cancer effect of pterostilbene (PSB) and 2’‐ and 3’‐hydroxypterostilbene (2HPSB and 3HPSB, respectively) on the JAK2/STAT3 pathway.

Methods and results

In vitro experiments with the OCCC cell line TOV21G and a xenograft nude mouse model are used to achieve the study aims. The results showed that 3HPSB has the greatest anti‐proliferative and pro‐apoptotic effects of the three compounds studied. Activation of the JAK2/STAT3 pathway and the nuclear translocation of STAT3 are effectively inhibited by 3HPSB and PSB. Both 3HPSB and PSB can effectively suppress tumor growth, which is mediated by the inhibition of JAK2/STAT3 phosphorylation.

Conclusion

This is the first study to compare the efficacy of PSB, 3HPSB, and the newly identified compound 2HPSB regarding ovarian cancer. Moreover, targeting JAK2/STAT3 is shown to be a potentially effective strategy for OCCC treatment. This study is expected to provide new insights into the potential of the abovementioned phytochemicals for development as adjuvants for cancer treatment in the future.
Does Flavonoid Supplementation Alleviate Non‐Alcoholic Fatty Liver Disease? A Systematic Review and Meta‐Analysis of Randomized Controlled Trials
Authors: Li Lu , Ji Kexin , Du Fengqi , Jin Nini , Boesch Christine , Farag Mohamed A. , Li He , Liu Xinqi , Xiao Jianbo
Published: October 2023

Scope

Higher flavonoid intake is associated with reduced risk of non‐alcoholic fatty liver disease (NAFLD). However, there is a large discrepancy in the effects of flavonoid supplementation on NAFLD. To fill such knowledge gap, we systematically reviewed randomized clinical trials (RCTs) to critically assess flavonoid supplementation effect on liver function, lipid profile, inflammation, and insulin resistance in adults with NAFLD.

Methods and results

A systematic search was conducted from 4 databases from inception until May 2023. Twelve RCTs were included in the final analysis demonstrating beneficial effects of flavonoids on ALT (SMD = −3.59, p = 0.034), AST (SMD = −4.47, p = 0.001), GGT (SMD = −8.70, p = 0.000), CK‐18M30 (SMD = −0.35, p = 0.042), TG (SMD = −0.37, p = 0.001), LDL‐C (SMD = −0.38, p = 0.039), TC (MD = −0.25 mmol/l, p = 0.017), steatosis score (MD = −18.97, p = 0.30), TNF‐α (MD = −0.88, p = 0.000), and NF‐κB (MD = −1.62, p = 0.001).

Conclusion

This meta‐analysis suggests that flavonoid alleviates NAFLD through exerting favourable effects on liver function, lipid profile, and inflammation, indicating flavonoid supplementation presents a promising drug regimen for the management of NAFLD and its associated complications.
High Plant Protein Diet Ameliorated Hepatic Lipid Accumulation Through the Modulation of Gut Microbiota
Authors: Zhu Shanshan , Zhao Yawen , Liu Ludi , Xu Yingxi , Zhu Jiangyuan , Li Wenkang , Liu Yan , Xia Min
Published: October 2023

Scope

Substituting plant protein for animal protein has emerged as a promising strategy for managing atherogenic lipids. However, the impact of long‐term intake of a high plant protein diet (HPD) on hepatic lipid disorder remains unclear.

Methods and results

Eight‐week‐old apolipoprotein E deficient (apoE−/−) mice are fed with either a normal protein diet (NCD) or HPD for 12 weeks. HPD intervention results in decreased body weight accompanied by increased energy expenditure, with no significant effect on glycemic control. Long‐term intake of HPD improves the serum and hepatic lipid and cholesterol accumulation by suppressing hepatic squalene epoxidase (SQLE) expression, a key enzyme in cholesterol biosynthesis. Integrated analysis of 16S rDNA sequencing and metabolomics profiling reveals that HPD intervention increases the abundance of the Lachnospiraece family and serum levels of 12,13‐DiHOME. Furthermore, in vivo studies demonstrate that 12,13‐DiHOME significantly inhibits lipid accumulation, as well as SQLE expression induced by oleic acid in HepG2 cells.

Conclusion

Diet rich in plant protein diet alleviates hyperlipidemia via increased microbial production of 12,13‐DiHOME.
The dirty and clean dose concept: Towards creating proton therapy treatment plans with a photon‐like dose response
Authors: Heuchel Lena , Hahn Christian , Ödén Jakob , Traneus Erik , Wulff Jörg , Timmermann Beate , Bäumer Christian , Lühr Armin
Published: October 2023

Background

Applying tolerance doses for organs at risk (OAR) from photon therapy introduces uncertainties in proton therapy when assuming a constant relative biological effectiveness (RBE) of 1.1.

Purpose

This work introduces the novel dirty and clean dose concept, which allows for creating treatment plans with a more photon‐like dose response for OAR and, thus, less uncertainties when applying photon‐based tolerance doses.

Methods

The concept divides the 1.1‐weighted dose distribution into two parts: the clean and the dirty dose. The clean and dirty dose are deposited by protons with a linear energy transfer (LET) below and above a set LET threshold, respectively. For the former, a photon‐like dose response is assumed, while for the latter, the RBE might exceed 1.1. To reduce the dirty dose in OAR, a MaxDirtyDose objective was added in treatment plan optimization. It requires setting two parameters: LET threshold and max dirty dose level. A simple geometry consisting of one target volume and one OAR in water was used to study the reduction in dirty dose in the OAR depending on the choice of the two MaxDirtyDose objective parameters during plan optimization. The best performing parameter combinations were used to create multiple dirty dose optimized (DDopt) treatment plans for two cranial patient cases. For each DDopt plan, 1.1‐weighted dose, variable RBE‐weighted dose using the Wedenberg RBE model and dose‐average LETd distributions as well as resulting normal tissue complication probability (NTCP) values were calculated and compared to the reference plan (RefPlan) without MaxDirtyDose objectives.

Results

In the water phantom studies, LET thresholds between 1.5 and 2.5 keV/µm yielded the best plans and were subsequently used. For the patient cases, nearly all DDopt plans led to a reduced Wedenberg dose in critical OAR. This reduction resulted from an LET reduction and translated into an NTCP reduction of up to 19 percentage points compared to the RefPlan. The 1.1‐weighted dose in the OARs was slightly increased (patient 1: 0.45 Gy(RBE), patient 2: 0.08 Gy(RBE)), but never exceeded clinical tolerance doses. Additionally, slightly increased 1.1‐weighted dose in healthy brain tissue was observed (patient 1: 0.81 Gy(RBE), patient 2: 0.53 Gy(RBE)). The variation of NTCP values due to variation of α/β from 2 to 3 Gy was much smaller for DDopt (2 percentage points (pp)) than for RefPlans (5 pp).

Conclusions

The novel dirty and clean dose concept allows for creating biologically more robust proton treatment plans with a more photon‐like dose response. The reduced uncertainties in RBE can, therefore, mitigate uncertainties introduced by using photon‐based tolerance doses for OAR.