bluuebunny/crossref_metadata_2025 huggingface dataset:
A NEW DOSE DETERMINATION METHOD FOR HP(3) AND DP LENS FOR BETA REFERENCE RADIATION QUALITIES
Authors: Teng Zhongbin , Song Mingzhe , Liu Senlin , Ni Nin , Wei Kexin , Liu Yuntao , Hang Zhongbin , Geng Xuan , Hu Kaixuan , Li Qiao , Jia Minghan , Li Dehong
Published: March 2023

For the purpose of obtaining the smaller uncertainties for Hp(3) and Dp lens in 90Sr/90Y beta reference fields, a new dose determination method based on the Monte-Carlo simulation was proposed. The conversion coefficients from the absorbed dose in air, at the reference point of the extrapolation ionisation chamber, Dair, det to Hp(3; α) and the conversion factors from Dair, det to Dp lens(α) were calculated with EGSnrc, respectively, for the irradiation angles from 0° to 60°. Compared with the dose determination method in International Organization for Standardization (ISO) 6980 standard, the uncertainty reductions of 7.7–52.8% for Hp(3; α) and 7.9–55.0% for Dp lens(α) were achieved, respectively. In addition, for the conversion coefficients from the reference absorbed dose DR to Hp(3; α), the calculations were performed for more irradiation conditions, which are not included in the current ISO 6980 standard. For the calculations of the conversion factors from DR to Dp lens(α), the eye and head phantoms with Chinese characteristics were utilised, which makes the conversion factors more suitable for use in China.
Long-term exposure to di(2-ethylhexyl) phthalate, diisononyl phthalate, and a mixture of phthalates alters estrous cyclicity and/or impairs gestational index and birth rate in mice
Authors: Laws Mary J , Meling Daryl D , Deviney Ashley R K , Santacruz-Márquez Ramsés , Flaws Jodi A
Published: March 2023

Phthalates are found in plastic food containers, medical plastics, and personal care products. However, the effects of long-term phthalate exposure on female reproduction are unknown. Thus, this study investigated the effects of long-term, dietary phthalate exposure on estrous cyclicity and fertility in female mice. Adult female CD-1 mice were fed chow containing vehicle control (corn oil) or 0.15–1500 ppm of di(2-ethylhexyl) phthalate (DEHP), diisononyl phthalate (DiNP), or a mixture of phthalates (Mix) containing DEHP, DiNP, benzyl butyl phthalate, di-n-butyl phthalate, diisobutyl phthalate, and diethyl phthalate. Measurements of urinary phthalate metabolites confirmed effective delivery of phthalates. Phthalate consumption for 11 months did not affect body weight compared to control. DEHP exposure at 0.15 ppm for 3 and 5 months increased the time that the mice spent in estrus and decreased the time the mice spent in metestrus/diestrus compared to control. DiNP exposure (0.15–1500 ppm) did not significantly affect time in estrus or metestrus/diestrus compared to control. Mix exposure at 0.15 and 1500 ppm for 3 months decreased the time the mice spent in metestrus/diestrus and increased the time the mice spent in estrus compared to control. DEHP (0.15–1500 ppm) or Mix (0.15–1500 ppm) exposure did not affect fertility-related indices compared to control. However, long-term DiNP exposure at 1500 ppm significantly reduced gestational index and birth rate compared to control. These data indicate that chronic dietary exposure to phthalates alters estrous cyclicity, and long-term exposure to DiNP reduces gestational index and birth rate in mice.
Kcnma1 is involved in mitochondrial homeostasis in diabetes‐related skeletal muscle atrophy
Authors: Gao Shan‐Yan , Liu Yong‐Ping , Wen Ri , Huang Xin‐Mei , Li Ping , Yang Yu‐Hang , Yang Ni , Zhang Tie‐Ning
Published: March 2023

Uncontrolled diabetes causes a catabolic state with multi‐organic complications, of which impairment on skeletal muscle contributes to the damaged mobility. Kcnma1 gene encodes the pore‐forming α‐subunit of Ca2+‐ and voltage‐gated K+ channels of large conductance (BK channels), and loss‐of‐function mutations in Kcnma1 are in regards to impaired myogenesis. Herein, we observed a time‐course reduction of Kcnma1 expression in the tibialis anterior muscles of leptin receptor‐deficient (db/db) diabetic mice. To investigate the role of Kcnma1 in diabetic muscle atrophy, muscle‐specific knockdown of Kcnma1 was achieved by mice receiving intravenous injection of adeno‐associated virus‐9 (AAV9)‐encoding shRNA against Kcnma1 under the muscle creatine kinase (MCK) promoter. Impairment on muscle mass and myogenesis were observed in m/m mice with AAV9‐shKcnma1 intervention, while this impairment was more obvious in diabetic db/db mice. Simultaneously, damaged mitochondrial dynamics and biogenesis showed much severer in db/db mice with AAV9‐shKcnma1 intervention. RNA sequencing revealed the large transcriptomic changes resulted by Kcnma1 knockdown, and changes in mitochondrial homeostasis‐related genes were validated. Besides, the artificial alteration of Kcnma1 in mouse C2C12 myoblasts was achieved with an adenovirus vector. Consistent results were demonstrated by Kcnma1 knockdown in palmitate‐treated cells, whereas opposite results were exhibited by Kcnma1 overexpression. Collectively, we document Kcnma1 as a potential keeper of mitochondrial homeostasis, and the loss of Kcnma1 is a critical event in priming skeletal muscle loss in diabetes.
Long non‐coding RNA SNHG11 regulates the Wnt/β‐catenin signaling pathway through rho/ROCK in trabecular meshwork cells
Authors: Liu Lu , Yang Xuejiao , Zhang Jingjing , Jiang Wenlan , Hou Tianyu , Zong Yao , Bai Haiqing , Yang Kun , Yang Xian
Published: March 2023

Trabecular meshwork (TM) cell dysfunction is the leading cause of elevated intraocular pressure (IOP) and glaucoma. The long non‐coding RNA (lncRNA) small nucleolar RNA host gene 11 (SNHG11) is associated with cell proliferation and apoptosis, but its biological functions and role in glaucoma pathogenesis remain unclear. In the present study, we investigated the role of SNHG11 in TM cells using immortalized human TM and glaucomatous human TM (GTM3) cells and an acute ocular hypertension mouse model. SNHG11 expression was depleted using siRNA targeting SNHG11. Transwell assays, quantitative real‐time PCR analysis (qRT‐PCR), western blotting, and CCK‐8 assay were used to evaluate cell migration, apoptosis, autophagy, and proliferation. Wnt/β‐catenin pathway activity was inferred from qRT‐PCR, western blotting, immunofluorescence, and luciferase reporter and TOPFlash reporter assays. The expression of Rho kinases (ROCKs) was detected using qRT‐PCR and western blotting. SNHG11 was downregulated in GTM3 cells and mice with acute ocular hypertension. In TM cells, SNHG11 knockdown inhibited cell proliferation and migration, activated autophagy, and apoptosis, repressing the Wnt/β‐catenin signaling pathway, and activated Rho/ROCK. Wnt/β‐catenin signaling pathway activity increased in TM cells treated with ROCK inhibitor. SNHG11 regulated Wnt/β‐catenin signaling through Rho/ROCK by increasing GSK‐3β expression and β‐catenin phosphorylation at Ser33/37/Thr41 while decreasing β‐catenin phosphorylation at Ser675. We demonstrate that the lncRNA SNHG11 regulates Wnt/β‐catenin signaling through Rho/ROCK via β‐catenin phosphorylation at Ser675 or GSK‐3β‐mediated phosphorylation at Ser33/37/Thr41, affecting cell proliferation, migration, apoptosis, and autophagy. Through its effects on Wnt/β‐catenin signaling, SNHG11 is implicated in glaucoma pathogenesis and is a potential therapeutic target.
Glucocorticoid exposure modifies the miRNA profile of sperm in the guinea pig: Implications for intergenerational transmission
Authors: Casciaro Christopher , Hamada Hirotaka , Kostaki Alisa , Matthews Stephen G.
Published: March 2023

Approximately 1%–3% of the adult population are treated with synthetic glucocorticoids (sGCs) for a variety of conditions. Studies have demonstrated that adversities experienced by males prior to conception may lead to abnormal neuroendocrine function and behaviors in offspring and that epigenetic factors including microRNA (miRNA) within sperm may be responsible for driving these effects. However, it remains unclear where in the epididymis sperm miRNA changes are occurring. Here, we hypothesized that sGC exposure will alter the miRNA profile of sperm in the epididymis in a region‐specific manner. Adult male guinea pigs were exposed to regular drinking water (Ctrl) or water with the sGC dexamethasone (Dex; 3mg/kg) (n = 6/group) every other day for 48 days. Sperms were collected from epididymal seminal fluid in the caput and cauda regions of the epididymis and total RNA was extracted. miRNAs were assessed by miRNA 4.0 microarray; data were processed by TAC 4.0.1 and R. miRNA analysis revealed one miRNA in the caput that was significantly decreased by Dex in sperm. In the cauda, 31 miRNAs were reduced in sperm following Dex‐exposure. The findings of this study demonstrate that Dex‐exposure influences miRNA profile of sperm in the cauda but not the caput of the epididymis. This suggests that glucocorticoids target the epididymis to modify sperm miRNA and do not modify the miRNA content during spermiation in the testes.
Cystic Lymphatic Malformation with Lymphedema Treated by Lymphaticovenular Anastomosis Combined with Ethanol Sclerotherapy
Authors: Yoshida Shuhei , Imai Hirofumi , Roh Solji , Mese Toshiro , Koshima Isao
Published: March 2023

The incidence of cystic lymphatic malformation (CL) in an extremity is very rare. CL can be a cause of lymphedema in a lower limb. The most effective treatment for CL is sclerotherapy or excision; however, these treatments have the potential to cause fibrosis and obliteration of ruptured lymphatic vessels, which impairs lymphatic drainage and increases the risk of lymphedema. Lymphaticovenular anastomosis (LVA) combined with sclerotherapy may be a minimally invasive treatment option for CL in a lower limb. In this report, we describe a patient with CL complicated by lymphedema in a lower extremity, who we treated using LVA and ethanol sclerotherapy with satisfactory results. The patient was a 60-year-old man with a CL measuring 16 cm in diameter in the thigh region above the knee with lower limb lymphedema. The percentage of excess volume of the affected lower leg was 24.7%, preoperatively. Combined treatment using LVA with sclerotherapy was performed under general anesthesia. At 2 years after surgery, the reduction of excess volume of affected lower leg between preoperative and postoperative was 85.4%. In our previous report, the same combination therapy was used to treat CL and prevent lymphedema; however, in the present case, it was used to treat CL and lymphedema at one stage. LVA combined with sclerotherapy is a complementary minimally invasive treatment for CL accompanied by lymphedema.
Hyaluronan in liver fibrosis: basic mechanisms, clinical implications, and therapeutic targets
Authors: Kim Jieun , Seki Ekihiro
Published: March 2023

Hyaluronan (HA), also known as hyaluronic acid, is a glycosaminoglycan that is a critical component of the extracellular matrix (ECM). Production and deposition of ECM is a wound-healing response that occurs during chronic liver disease, such as cirrhosis. ECM production is a sign of the disease progression of fibrosis. Indeed, the accumulation of HA in the liver and elevated serum HA levels are used as biomarkers of cirrhosis. However, recent studies also suggest that the ECM, and HA in particular, as a functional signaling molecule, facilitates disease progression and regulation. The systemic and local levels of HA are regulated by de novo synthesis, cleavage, endocytosis, and degradation of HA, and the molecular mass of HA influences its pathophysiological effects. However, the regulatory mechanisms of HA synthesis and catabolism and the functional role of HA are still poorly understood in liver fibrosis. This review summarizes the role of HA in liver fibrosis at molecular levels as well as its clinical implications and discusses the potential therapeutic uses of targeting HA in liver fibrosis.
Prediction and prevention of the first episode of overt hepatic encephalopathy in patients with cirrhosis
Authors: Gairing Simon J. , Schleicher Eva M. , Galle Peter R. , Labenz Christian
Published: March 2023

Hepatic encephalopathy (HE) is one of the most important complications of patients with liver cirrhosis. In addition, HE is associated with a dismal prognosis and has detrimental effects on patients’ quality of life. Thus, it is of pivotal importance to identify patients at high risk for overt HE (OHE) in whom primary prophylaxis may be justified. In this narrative review, we aim to provide insight into predictors and prediction tools for a first-time episode of OHE and to scrutinize the current level of evidence of primary prophylaxis. In recent decades, several cognitive tests, composite scores, and blood-based biomarkers have been demonstrated to be predictive of a first-time episode of OHE. Among the best validated are the established tests for minimal HE, such as the Psychometric Hepatic Encephalopathy Score, determination of the critical flicker frequency, Stroop EncephalApp, or the Animal Naming Test. Individualized risk stratification using blood-based biomarkers and cross-sectional imaging (sarcopenia and spontaneous portosystemic shunts) is coming to the fore, but validation in larger multicenter cohorts is often lacking. On the basis of current evidence, a recommendation for primary prophylaxis of a first episode of OHE cannot be made in general. Only 2 studies have investigated the prevention of a first-time OHE episode as the primary endpoint. In this narrative review, we provide a concise overview of the current evidence levels on prediction tools and pharmacological prevention of a first episode of OHE. In addition, we give an outlook on future research targets to improve knowledge on this important topic.
Measuring hepatitis B pgRNA stability using an updated automated HBV pgRNA assay with increased sensitivity
Authors: Anderson Mark , Stec Michael , Thi Emily P. , Picchio Gaston , Mbanya Dora , Cloherty Gavin
Published: March 2023

Background:

HBV pregenomic RNA (pgRNA) is a circulating biomarker for covalently closed circular DNA activity in HBV-infected individuals and has been studied for treatment efficacy, disease staging, and off-therapy outcomes; however, data on the stability are scarce. Increasing HBV pgRNA assay sensitivity may improve its predictive value and provide additional insights at low viral levels.

Methods:

Modifications to a fully automated first (v1) generation HBV pgRNA assay improved sensitivity up to 15-fold over the previous assay. Flexible sample input volumes yielded lower limits of quantitation of 10 and 22 copies/mL for 0.6 and 0.2 mL assays, respectively. Results are standardized to secondary standards that are traceable to the WHO HBV DNA standard, and internal and external controls are included.

Results:

Comparison between v1 and modified v2 assays showed increased sensitivity from 152 copies/mL with v1 to 10 (0.6 mL) and 22 (0.2 mL) copies/mL with v2, respectively. Quantitated v2 results were indistinguishable from v1, indicating that comparisons can be made to previous studies. Single timepoint treatment-naive blood donors or longitudinal draws from patients with chronic hepatitis B on AB-729, an investigational siRNA therapy, showed improved detection and quantifiable pgRNA with v2 compared with v1. Stability testing demonstrated excellent HBV pgRNA plasma stability after 3 freeze-thaw cycles, for at least 7 days at 25–37 °C and at least 30 days at 4°C, with ≤0.25 Log U/mL decrease.

Conclusion:

HBV pgRNA v2 assays with increased sensitivity and flexible input volumes demonstrated increased detection and quantitation of low viral titer samples. Highly sensitive HBV pgRNA assays may be useful in refining predictive treatment outcomes based on this marker. HBV pgRNA was stable under multiple conditions, which increases the reliability of this marker.
TEMPORAL EFFICACY AND STERILITY TESTING OF POVIDONE-IODINE FROM AN OPEN BOTTLE
Authors: Yousuf Salman J. , Alfaqih Murad , Hicken Rachel , Ramadan Ali
Published: March 2023

Purpose:

To investigate the temporal efficacy and sterility of povidone-iodine (PI) against bacteria associated with postinjection endophthalmitis in an in vitro study.

Methods:

A single PI bottle was opened and tested for sterility and antibacterial efficacy. Povidone-iodine from the open bottle was inoculated onto a blood agar plate and evaluated for growth 24 hours later to test sterility; this was repeated for five consecutive days. To test for antibacterial efficacy, PI was instilled onto the surface of plates of Staphylococcus, Streptococcus, Enterococcus, Pseudomonas, and Haemophilus species. The plates were then evaluated 24 hours later for a clear zone of inhibition (i.e., no growth) where the PI was placed. This process was repeated for five consecutive days.

Results:

Sterility testing showed no growth of organisms on the blood agar plates for each of the five days of testing. For antibacterial efficacy testing, zones of inhibition of growth were seen on each plate of bacterial colonies only where PI was placed, for each of the five days of testing.

Conclusion:

In this study, PI from an open bottle maintained its sterility and antibacterial efficacy for five days. These data could help support repeated use of the same bottle, reducing waste and costs for retina practices.
Retinal Nerve Fiber Layer Thickness/Minimum Rim Width Ratio Differentiates Glaucoma From Other Optic Neuropathies
Authors: Boussion François , Guindolet Damien , Deschamps Romain , Lamirel Cédric , Vignal-Clermont Catherine
Published: March 2023

Précis:

Global peripapillary retinal nerve fiber layer thickness (pRNFL)/Bruch membrane opening–minimum rim width (BMO–MRW) ratio is an objective and effective parameter to separate glaucomatous optic neuropathies (GONs) from nonGONs (NGONs).

Purpose:

This study was undertaken to evaluate the diagnostic capability of the pRNFL/ BMO–MRW ratio to differentiate GONs from NGONs.

Patients and Methods:

This retrospective study included patients with an optic neuropathy (ON), visual loss for>6 months and a confirmed single etiology. pRNFL thickness and BMO–MRW were measured with spectral-domain optical coherence tomography (Spectralis, Heidelberg Engineering, Heidelberg, Germany). The diagnostic accuracies of pRNFL, BMO–MRW and the global pRNFL/BMO–MRW ratio were evaluated with the areas under receiver operating characteristics curves.

Results:

One eye each from 171 patients was investigated: 50 primary open angle glaucomas, 15 normal pressure glaucomas, 50 optic neuritises, 15 nonarteritic anterior ischemic ONs, 24 compressive ONs, 10 dominant optic atrophies, and 7 nutritional ONs. The global pRNFL/BMO–MRW ratio had the highest area under receiver operating characteristics curve [0.97 vs. 0.92; P=0.01]. It was able to distinguish between GONs and NGONs with a cutoff value of 0.34. Increased mean deviation of the visual field-defect severity was associated with a higher ratio for GONs and a lower ratio for NGONs.

Conclusion:

Compared with NGONs and for the same degree of pRNFL thinning, lower BMO– MRW was found to be a specific marker of glaucoma, reflecting the neuroglial architecture changes within the optic nerve head typical of glaucoma and supporting fundamental pathophysiological differences.
Five-Year Clinical Outcomes of Inferior Quadrant Trabectome Surgery for Open Angle Glaucoma
Authors: Weber Constance , Ludwig Elisabeth , Hundertmark Sarah , Brinkmann Christian Karl , Petrak Michael , Holz Frank G. , Mercieca Karl
Published: March 2023

Précis:

This retrospective study of 264 eyes having inferior quadrant trabectome surgery confirms its safety and relative effectiveness. Most patients however still require IOP-lowering agents, and a considerable proportion may need additional glaucoma surgery.

Purpose:

To report outcomes from a large single-center cohort of inferiorly-applied trabectome surgery.

Patients and Methods:

Retrospective review of patients undergoing trabectome surgery for chronic open angle glaucoma (COAG) at the University Eye Clinic Bonn, Germany, from 2012 to 2020.

Results:

Two hundred sixty-four eyes of 206 patients with COAG were included. The mean review period was 45.43 (range 12–101) months. One hundred five eyes (39.8%) underwent standalone surgery, of which 74 were pseudophakic and 31 phakic. The mean preoperative IOP was 17.58 mm Hg (range 12–50 mm Hg). One hundred five eyes (39.8%) developed a ‘failure event’ according to pre-defined criteria at a mean interval of 14.8 months postoperative. In absolute terms, 211 patients (79.9%) had a long-term IOP >14 mm Hg at 7.6 months, 174 patients (65.9%) >16 mm Hg at 10.6 months, 127 patients (48.1%) >18 mm Hg at 10.9 months, and 77 patients (29.2%) >21 mm Hg at 11.1 months. Over a five-year period, overall mean IOP remained stable at 13 mm Hg. The majority of patients were still on glaucoma drops (the mean number reduced from 2.9 to 2.7 agents). Subgroup analyses showed that a higher preoperative IOP was a positive predictor for failure, whereas combined surgery (with phaco) had better IOP outcomes (16.5 mm Hg vs. 19.3 mm Hg, respectively). Forty-one patients (15.5%) developed minor complications: 22 had high postoperative IOP within 3 months, 11 developed a self-resorbing hyphema, and 6 had fibrinous uveitis.

Conclusions:

Trabectome surgery is a safe and relatively effective procedure for lowering IOP, but most patients still need IOP-lowering agents, and a considerable proportion may need additional glaucoma surgery within a relatively short time. Inferior quadrant treatment may result in inferior IOP outcomes when compared with nasal quadrant surgery.
Effect of Online Instruction on the Level of Knowledge About Clostridium difficile Infection Among Undergraduate Nursing Students in a Developing Country
Authors: Najjar Yahya W. , Hassan Zeinab M. , Al-saraireh Mahmoud M.
Published: March 2023

Background

Clostridium difficile infection is a life-threatening hospital-acquired infection worldwide. Nursing students need to be able to identify patients who have a high chance of contracting C. difficile infection. The study objective is to determine the level of knowledge on C. difficile infection before and after online instruction in undergraduate nursing students.

Methods

A group pretest-posttest design was implemented to measure the effectiveness of an online instructional program, in which 170 nursing students participated in this study. The level of knowledge was assessed by the percentage of correct answers in the following subsections: (a) basic knowledge; (b) risk factors; (c) modes of transmission; and (d) infection control measures, by using a questionnaire that contained 20 true/false statements.

Results

Overall, the nurses in this study had a low level of knowledge about C. difficile pre–online instruction and a significant increase in knowledge regarding C. difficile infection in all sections after online instruction.

Conclusions

Online instruction should be integrated into the undergraduate nursing curriculum in developing countries. Self-directed instruction is an effective approach for nursing students to teach them infectious diseases in developing countries.
A Unique Case of Purulent Malignant Otitis Externa Causing Community-Acquired Klebsiella Pneumonia Meningitis in a Marshallese Male
Authors: Belote Alex , Conde Daniel , Young Daniel
Published: March 2023

Bacterial meningitis secondary to malignant otitis externa is a rare but dreaded complication. Malignant otitis externa typically results from infection with Pseudomonas aeruginosa. Community-acquired bacterial meningitis most commonly stems from Streptococcus pneumoniae or Neisseria meningitidis. We report a unique case of community-acquired Klebsiella pneumoniae meningitis, a rare culprit in the United States. Klebsiella pneumoniae disproportionally affects people of Southeast Asian descent. Dramatically increased rates of K. pneumoniae infection have been reported in Asian countries and in expatriates living abroad. Our case afflicted a 48-year-old man originally from the Marshall Islands residing in the United States. This case displays a unique constellation of anomalies and afflictions, including extension from MOE, bacteremia, facial nerve paralysis, dural sinus thrombosis, and rapid recovery.
Comparison of the Performance of the CURB-65, A-DROP, and NEWS Scores for the Prediction of Clinical Outcomes in Pneumonia
Authors: Bastidas Goyes Alirio , Aponte Carolina , Acosta David , Barroso Da Silva Erika Alexandra , Tuta Quintero Eduardo , Gómez Carolina , Mantilla Flórez Fabian , Rodríguez Santiago , Álvarez David , Hernández Esteban , Ramírez Laura , Riveros Paola , Álvarez Daniela , Forero Julián , Gutiérrez Felipe , Moscote Adriana , Oke Gebran
Published: March 2023

Objectives

This study aimed to compare the performance of the CURB-65, A-DROP, and NEWS scores for the prediction of clinical outcomes in patients with community-acquired pneumonia (CAP) in a Colombian population.

Materials and Methods

In this retrospective cohort study, we analyzed data from patients with CAP seen within the emergency department, general ward hospitalization, and intensive care unit in a tertiary care health institution located in Cundinamarca, from January 2012 to December 2020.

Results

A total of 1651 patients were included in our study. CURB-65 and A-DROP scores showed a good performance for primary outcomes related to in-hospital mortality and 30-day mortality with an area under the receiver operating characteristic curve (AUC-ROC) of 0.72 (95% confidence interval [CI], 0.69–0.76) and 0.69 (95% CI, 0.65–0.73), respectively. On the other hand, NEWS score exhibited an acceptable performance in predicting in-hospital mortality and 30-day mortality; furthermore, it showed better performance in anticipating the need for invasive mechanical ventilation and vasopressor therapy (AUC-ROC of 0.64 [95% CI, 0.59–0.69] and AUC-ROC of 0.65 [95% CI, 0.60–0.69], respectively).

Conclusions

Our findings suggest that, in patients with CAP, the use of CURB-65, A-DROP, and NEWS scores helps the clinician to predict in-hospital and 30-day mortality. However, NEWS score proves to be a more convenient tool to predict the need for several life support measures and management in the intensive care unit.
Underestimating a Dog Bite
Authors: Amadori Francesco , Fabiani Silvia , Lenzi Mirco , Forniti Arianna , Ferranti Simone , Tagliaferri Enrico
Published: March 2023

Dog bites may result in serious bacterial infections because of various microorganisms, including gram-negative rod Capnocytophaga canimorsus, whose disease can be complicated by acute development of sepsis and/or meningitis. In this review, we report a case of C. canimorsus meningitis in a patient with major risk factors and subsequently analyze 48 other cases described in literature. Approximately a little less than 50% of reported cases had a major predisposing condition such as splenectomy, alcoholism, or immunosuppressive treatment. In almost all of the cases, recent animal exposure was reported. Sensorineural hearing loss, which has been described as a permanent complication of C. canimorsus meningitis, was present in a minority of cases (18%), and a possible association with alcoholism was observed. In conclusion, C. canimorsus should be considered as a possible cause of sporadic meningitis in adults, particularly if presenting with a subacute course or deafness and in concomitance of major predisposing conditions, such as alcoholism.
Correlation of N-terminal-pro-brain natriuretic peptide with postoperative outcomes of older patients undergoing transcatheter aortic valve replacement
Authors: Huang Ying-Ching , Chang Hsiao-Huang , Chen Po-Lin , Chu Chi-Ming , Tsai Jen-Chen , Wang Kwua-Yun
Published: March 2023

Background:

Patients undergoing transcatheter aortic valve replacement surgery (TAVR) are typically older adults with multiple chronic diseases and therefore have a high surgical risk. The N-terminal of brain natriuretic peptide (BNP) and pro-BNP, referred to as NT-pro-BNP, is an easily measurable biomarker of heart failure. Studies on correlation between higher NT-pro-BNP levels and adverse prognoses after TAVR have yielded inconsistent results. Here, we investigated whether preoperative NT-pro-BNP levels are correlated with outcomes among older adults undergoing TAVR.

Methods:

This retrospective study included older adults with severe aortic stenosis (AS) who received TAVR from a medical center between January 2013 and June 2017. The patients’ demographics, preoperative laboratory data, postoperative complications, and 1-year mortality were recorded. They were divided into two groups based on their preoperative NT-pro-BNP levels. The post-TAVR outcomes in the two groups were analyzed using a multivariate logistic regression analysis of the binary results.

Results:

Of the 132 patients included (mean age: 81.5 ± 8.1 years; 47% men), 96 (72.7%) had preoperative NT-pro-BNP levels ≤ 4853 ng/L, and 36 (27.3%) had preoperative NT-pro-BNP levels > 4853 ng/L. The postoperative outcomes were significantly better in the NT-pro-BNP≤4853 group than in the NT-pro-BNP>4853 group: postoperative extracorporeal membrane oxygenation fittings (4.2% vs 16.7%, p = 0.025), number of days in hospital (17.5 ± 21.0 vs 27 ± 17.0, p = 0.009), in-hospital mortality (4.2% vs 16.7%, p = 0.025), and 1-year mortality (11.5% vs 38.9%, p = 0.001); the significant differences persisted after controlling for other variables.

Conclusion:

For older patients undergoing TAVR with NT-pro-BNP levels > 4853 ng/L, their postoperative outcomes and 1-year mortality were correlated. Thus, NT-pro-BNP is useful for the risk assessment of patients undergoing TAVR and should be regarded as a biomarker in future risk assessments.
Cutaneous Manifestations of Scleroderma
Authors: Aggarwal Manushi , Sandhu Vaneet Kaur
Published: March 2023

Scleroderma is a rare, female predominant clinically heterogenous, autoimmune condition characterized by the presence of autoantibodies, vascular abnormalities, and fibrosis. Skin thickening as a result of fibrosis is a hallmark clinical finding, and the extent of this skin thickening further classifies clinical subsets of scleroderma. Organ systems affected may include pulmonary (interstitial lung disease, pulmonary arterial hypertension), renal (scleroderma renal crisis), gastrointestinal (dysmotility, reflux esophagitis, gastric antral vascular ectasia), cardiac (arrhythmias, cardiac fibrosis), and musculoskeletal (arthritis, contractures). Raynaud phenomenon and telangiectasis occur as a result of vascular involvement. Diagnostic workup requires a thorough history and physical examination, supplemented by autoantibody testing. No single therapeutic agent is indicated to treat all manifestations of scleroderma. Rather, system- or organ-based treatment is indicated. Not only are skin manifestations often the presenting feature of scleroderma, progressive skin changes carry prognostic implications, underscoring the value of dermatology insight for early diagnosis suspicion, referral to rheumatology, and timely management.
Lichen Sclerosus
Authors: Reddy Meenu , O'Connell Katie A. , O'Connor Megan
Published: March 2023

Lichen sclerosus is a chronic inflammatory condition characterized by irritation and dyspigmentation in the genital and perianal areas. Although this condition can affect any individual, it typically has a bimodal age distribution, occurring most frequently in postmenopausal women followed by prepubertal children. Physical examination often reveals thin, hypopigmented and hyperpigmented patches or plaques in the vulvar, perineal, or perianal region. The exact etiology of lichen sclerosus is unknown but is believed to be multifactorial with a combination of genetic, environmental, infectious, and autoimmune factors. Once diagnosed, this condition has a chronic course and long-term treatment is required to sustain remission. We present a case of lichen sclerosus involving the vulvar, perineal, and perianal regions in an elderly female patient that improved with topical clobetasol.
A Case of Transient Eruptive Keratoacanthoma Associated With Nivolumab
Authors: Irwin Thomas M. , Burkett Kristen M. , Johnson Emily , Bodenhamer William Spence , Wood Andrew , Fraga Garth R. , Doolittle Gary C.
Published: March 2023

Anti-PD-1 immunotherapy agents are known to cause cutaneous side effects in up to 42% of patients with melanoma, infrequently including eruptive keratoacanthomas (de Golian et al., 2016, p. 57). Although traditionally documented with pembrolizumab use, increasing reports of eruptive keratoacanthomas with nivolumab use are emerging in the literature (Bednarek et al., 2018, pp. e28–e29). We present a similar case of a 74-year-old woman with melanoma of the right upper extremity with metastases to the lung. She received her first infusion of nivolumab and, within 2 weeks, developed a pruritic rash on the right arm. Within 1 month, the rash spread to all extremities and would blister, scale, and slough off. Punch biopsy of the right lower extremity revealed squamous proliferation suspicious for eruptive keratoacanthoma secondary to nivolumab therapy. The patient continued nivolumab and was referred to dermatology to monitor.
Meta-analysis of clinical risk factors of patients with systemic lupus erythematosus complicated with invasive fungal infection
Authors: Meng Yang , Chifeng Liao , Qinghuan Zhu , Zichan Huang , Jianmin Li , Danqi Deng
Published: March 2023

Background:

To systematically evaluate the clinical risk factors of patients with systemic lupus erythematosus (SLE) complicated with invasive fungal infection (IFI) among patients.

Methods:

A meta-analysis was performed of all the literatures germane to estimate the clinical risk factors of patients with SLE complicated with IFI from published clinical trials from 1990 to April 2022. Mean differences, odds ratio and 95% confidence intervals were calculated, and the meta-analysis was conducted with Stata 12.0 software (StataCorp, College Station, TX).

Results:

A total of 14 clinical research involving 1129 patients were included. The results of meta-analysis demonstrated that immunosuppressant, glucocorticoids, systemic lupus erythematosus disease activity index score, antibiotic were risk factors associated with IFI in SLE patients. However, age, sex, course of disease, leukopenia, lymphopenia, C- reactive protein and hypoproteinemia were not the risk factors associated with IFI in patients with SLE.

Conclusion:

Our results indicate that immunosuppressant, glucocorticoids, systemic lupus erythematosus disease activity index score, antibiotic were risk factors for IFI in SLE patients. However, high quality of multicenter, large sample size-controlled trials are needed to validate the result.
Patent foramen ovale-associated stroke repeatedly misdiagnosed as cerebral small vessel disease: A case report
Authors: Zhang Yiwen , Zhu Ruihan , Yu Zhenzhen , Hou Songqi , Niu Jianping
Published: March 2023

Background:

Transthoracic echocardiography (TTE) is the most commonly used screening method for cardiac structural abnormalities. However, it may lead to a missed diagnosis of partial patent foramen ovale (PFO)-associated stroke.

Case presentation:

A 60-year-old male was admitted to the hospital for recurrent left limb weakness with or without slurred speech for 14 months. No stroke-related cardiac structural abnormality was detected during repeated TTE, and the patient was diagnosed with cerebral small vessel disease. Finally, right-to-left shunt was detected by contrast-enhanced transcranial Doppler. Subsequently, the patient was diagnosed with PFO-associated stroke by transesophageal echocardiography and contrast transesophageal echocardiography.

Conclusions:

TTE has a low detection rate of PFO, such that it is easily missed. Contrast-enhanced transcranial Doppler is easy to operate and should be promoted as a supplementary measure to stroke etiological investigation and primary PFO screening.
Expansion and characterization of regulatory T cell populations from Korean kidney transplant recipients
Authors: Paek Jin Hyuk , Kim Ye Na , Shin Ho Sik , Jung Yeonsoon , Rim Hark
Published: March 2023

The development of immunosuppressants has enabled remarkable progress in kidney transplantation (KT). However, current immunosuppressants cannot induce immune tolerance, and their nonspecific immunosuppressive effects result in many adverse effects. Regulatory T cells (Tregs) play crucial roles in controlling all specific immune responses. This study evaluated the distribution of Tregs and their effects on kidney allograft function in Korean KT recipients. We enrolled 113 KT recipients with stable graft function. The differentiation and expansion of Tregs were examined by flow cytometry to compare the Tregs subpopulations. Among the 113 patients, 73 (64.6%) were males, and the mean follow-up period from KT to Tregs collection was 147.5 + 111.3 months. Patients receiving lower doses of cyclosporine had higher proportions of Tregs than those with higher doses of cyclosporine (36.3 + 21.6 vs 17.0 + 12.7, P = .010, respectively). Patients taking cyclosporine tended to have higher Tregs numbers than those taking tacrolimus (94.7 + 158.1 vs 49.3 + 69.4, P = .095, respectively). However, no significant association was observed between Tregs and allograft dysfunction in the cox proportional hazard model. Tregs counts may be associated with the type and dose of immunosuppressants. However, no significant relationship was found between Tregs and kidney allograft function in stable KT recipients.
CeRNA network identified hsa-miR-17-5p, hsa-miR-106a-5p and hsa-miR-2355-5p as potential diagnostic biomarkers for tuberculosis
Authors: Song Jie , Sun Jiaguan , Wang Yuqing , Ding Yuehe , Zhang Shengrong , Ma Xiuzhen , Chang Fengxia , Fan Bingdong , Liu Hongjuan , Bao Chenglan , Meng Weimin
Published: March 2023

This study aims to analyze the regulatory non-coding RNAs in the pathological process of tuberculosis (TB), and identify novel diagnostic biomarkers. A longitudinal study was conducted in 5 newly diagnosed pulmonary tuberculosis patients, peripheral blood samples were collected before and after anti-TB treatment for 6 months, separately. After whole transcriptome sequencing, the differentially expressed RNAs (DE RNAs) were filtrated with |log2 (fold change) | > log2(1.5) and P value < .05 as screening criteria. Then functional annotation was actualized by gene ontology enrichment analysis, and enrichment pathway analysis was conducted by Kyoto Encyclopedia of Genes and Genomes database. And finally, the competitive endogenous RNA (ceRNA) regulatory network was established according to the interaction of ceRNA pairs and miRNA-mRNA pairs. Five young women were recruited and completed this study. Based on the differential expression analysis, a total of 1469 mRNAs, 996 long non-coding RNAs, 468 circular RNAs, and 86 miRNAs were filtrated as DE RNAs. Functional annotation demonstrated that those DE-mRNAs were strongly involved in the cellular process (n = 624), metabolic process (n = 513), single-organism process (n = 505), cell (n = 651), cell part (n = 650), organelle (n = 569), and binding (n = 629). Enrichment pathway analysis revealed that the differentially expressed genes were mainly enriched in HTLV-l infection, T cell receptor signaling pathway, glycosaminoglycan biosynthesis-heparan sulfate/heparin, and Hippo signaling pathway. CeRNA networks revealed that hsa-miR-17-5p, hsa-miR-106a-5p and hsa-miR-2355-5p might be regarded as potential diagnostic biomarkers for TB. Immunomodulation-related genes are differentially expressed in TB patients, and hsa-miR-106a-5p, hsa-miR-17-5p, hsa-miR-2355-5p might serve as potential diagnostic biomarkers.
IKZF3 is a novel prognostic biomarker for head and neck squamous cell carcinoma: A study based on bioinformatics analysis
Authors: Li Hongxiang , Ye Mengmeng , Hu Zeyang , Lu Haoxuan , Zheng Dawei , Wu Mi , Ge Ting , Xu Shuguang , Ge Zhen , Zhang Shuoni , Xu Guodong , Chen Hang
Published: March 2023

In the past few years, immunotherapy of tumors has become an extensive research hotspot, and the value of IKZF family genes in the tumor microenvironment has also been increasingly recognized. However, the expression of the IKAROS family zinc finger 3 (IKZF3) gene in human head and neck squamous cell carcinoma (HNSCC) and its prognostic value were not reported for the main subset until now. In the present study, we analyzed the relationship between IKZF3 gene expression and the survival of HNSCC patients. To evaluate the potential of IKZF3 as a prognostic biomarker for HNSCC comprehensively, multiple online analysis tools, including UALCAN, cBioPortal, GEPIA, WebGestalt, String, Genomic Data Commons, and TIMER databases were utilized in our study. We observed that the HNSCC patients with higher IKZF3 expression tended to exhibit longer overall survival. Univariate and multivariate Cox regression analyses indicated that age and grade were independent prognostic indicators in HNSCC. Moreover, Gene Ontology and KEGG function enrichment analyses showed that several pathways in HNSCC might be pivotal pathways regulated by IKZF3, which revealed that IKZF3 was probably participating in the occurrence and development of HNSCC. Furthermore, the hypomethylation of the IKZF3 gene was closely associated with genes that observed mutation in HNSCC. IKZF3 was significantly correlated with several immune cells in HNSCC (e.g., CD8+ T cell, CD4+ cell, and dendritic cell). We explored the potential prognostic values and roles of the IKZF3 in HNSCC, revealing that IKZF3 was probably a novel and reliable prognostic biomarker for patients with HNSCC.
An integrative pan-cancer analysis illustrating the key role of LRP11 in cervical cancer
Authors: Gu Fangyun , Xu Fang , Pan Zimeng , Shi Lin , Yu Jinglu , Song Feifei , Huang ShuFeng , Sun Miao
Published: March 2023

Background:

Low density lipoprotein receptor-related protein 11 (LRP11) was involved in the progression of several tumors. However, its role in cervical cancer still remains uncertain.

Methods:

The original tumor data was downloaded from the Cancer Genome Atlas and genotype-tissue expression databases. The expression of LRP11 in normal tissues, tumor tissues and adjacent tissues were evaluated. In addition, we also explored the genetic alteration, prognostic value, and gene function of LRP11. We deeply assessed the interaction between LRP11 and tumor immunity at the pan-cancer level. Finally, research on the association between LRP11 and the resistance of anti-tumor drugs was carried out.

Results:

LRP11 was highly expressed and played a risk prognostic factor in cervical cancer and a variety of tumors. Enrichment analysis revealed that LRP11 was involved in multiple tumor malignant pathways. Our research also pointed out the unique role between LRP11 and tumor immune microenvironment. The tumor immune microenvironment of patients with high expression of LRP11 are lack of most immune cells, indicating a immune desert tumor microenvironment. The final drug resistant analysis suggested that patients with high expression of LRP11 may be related to the resistance of many anti-tumor drugs.

Conclusion:

LRP11 was a potential oncogene and prognostic marker in cervical cancer and pan-cancer. Patients with high LRP11 expression may have immune desert tumor microenvironment.
Association of beta-2-microglobulin with cardiovascular and all-cause mortality in the general and non-CKD population
Authors: Fang Hang , Zhang Qiankun , Jin Lie
Published: March 2023

β-2 microglobulin, a light chain in the major histocompatibility complex Class 1 molecule, is associated with mortality in dialysis or uremic patients. Current evidence on the relationship between beta-2-microglobulin (B2M) and mortality in the general and non-chronic kidney disease (CKD) population are limited and controversial. Data from the nutrition and health examination survey database and the nutrition and health examination survey linked mortality file were used. In total, 10,388 adults who had complete data for B2M were included. Weighted multivariable Cox proportional hazards regression models and regression splines were employed to evaluate the relationship between B2M with mortality. Moreover, subgroup and sensitivity analyses were performed. During a median follow up of 17.9 years (interquartile range 15.2–18.7), 2780 people died, 902 (32%) from cardiovascular disease. Restricted cubic splines showed that B2M is J-shaped nonlinear positively associated with all-cause mortality and cardiovascular disease mortality in the non-CKD and general population. Based on the multivariable adjustment model, the adjusted hazard ratios comparing the highest versus lowest quartile of the distribution of B2M were 2.50 (95% confidence interval: 1.90, 3.28) for all-cause mortality in the general population, 2.58 (95% confidence interval: 1.52, 4.37) for cardiovascular disease mortality in the general population, 2.58 (1.91, 3.49) for all-cause mortality in the non-CKD population and 2.62 (1.52, 4.53) for cardiovascular disease mortality in the non-CKD population. The positive associations between B2M and outcomes remained broadly significant across subgroups and sensitivity analyses. Higher B2M levels were associated with cardiovascular and all-cause mortality in the general and non-CKD population.
Clinical evaluation of total hip arthroplasty for osteoarthropathy secondary to septic hip arthritis
Authors: Ye Xiguang , Zeng Jing , Liu Yongguo , Wang Jie
Published: March 2023

To investigate the clinical efficacy and prognosis of total hip arthroplasty (THA) in patients with osteoarthropathy secondary to septic hip arthritis. A total of 100 patients with osteoarthropathy secondary to septic hip arthritis who underwent surgery in our hospital from December 2010 to December 2021 were selected. Operative data were summarized. Moreover, preoperative and postoperative differences in Harris score, Western Ontario and McMaster Universities Osteoarthritis Index score, Visual Analogue Scale score, hip mobility were compared. Due to hospital transfer, the epidemic of COVID-2019 and other reasons, 10 patients were lost to follow-up and finally 90 patients were recorded. According to the results, the mean operation time (OT) was 1.78 ± 0.32 (hour), the mean intraoperative blood loss (BL) was 586.62 ± 31.66 (mL), the mean red blood cell (RBC) transfusion was 3.84 ± 0.75 (U), and 2 cases were positive, and 88 cases were negative for Trendelenburg sign. Postoperatively, the unequal length of the lower limbs and the Visual Analogue Scale score were significantly lower than that of the preoperative, while the Western Ontario and McMaster Universities Osteoarthritis Index score, Harris score, and hip joint range of motion were significantly higher than those of the preoperative (P < .05). At the last follow-up, all the incisions healed with no deep infections, 1 case suffered from transient sciatic nerve palsy, 2 cases had intermuscular venous thrombosis, and 2 cases who occurred hip dislocation recovered after treatment. THA surgery for osteoarthropathy secondary to septic hip arthritis has a good effect, relieving the patient’s pain effectively, improving prognosis and joint mobility. For osteoarthropathy secondary to septic hip arthritis, THA may be meaningful in terms of prognosis.