bluuebunny/crossref_metadata_2025 huggingface dataset:
Microbial Biomarkers for Lung Cancer: Current Understandings and Limitations
Authors: Huang Jiawen , Huang Juan
Published: December 2022

As our “hidden organ”, microbes widely co-exist at various sites on the human body. These microbes are collectively referred to as the microbiome. A considerable number of studies have already proven that the microbiome has significant impacts on human health and disease progression, including cancers. The recent discovery of cancer-specific microbiomes renders these cancer-associated microbes as potential biomarkers and therapeutic targets. While at low biomass levels, the lung microbiome still dramatically influences the initiation, progression and treatment of lung cancers. However, research on lung cancer-associated microbiomes is emerging, and most profiling studies are performed within three years. Unfortunately, there are substantial inconsistencies across these studies. Variations in microbial diversity were observed, and different microbial biomarkers for lung cancer have been proposed. In this review, we summarized the current findings of lung cancer microbiome studies and attempt to explain the potential reasons for the dissimilarities. Other than lung microbiomes, oral and airway microbiomes are highly related to lung microbiomes and are therefore included as well. In addition, several lung cancer-associated bacterial genera have been detected by different independent studies. These bacterial genera may not be perfect biomarkers, but they still serve as promising risk factors for lung cancers and show great prognostic value.
Performance of Scoring Systems in Predicting Clinical Outcomes of Patients with Emphysematous Pyelonephritis: A 14-Year Hospital-Based Study
Authors: Chen Chun-Cheng , Hsieh Ming-Shun , Hu Sung-Yuan , Huang Shih-Che , Tsai Che-An , Tsai Yi-Chun
Published: December 2022

Background: Emphysematous pyelonephritis (EPN) is a rare but severe necrotizing infection causing there to be gas in the pelvicalyceal system, renal parenchyma, and perirenal or pararenal space. Physicians should attend to EPN because of its life-threatening septic complications. The overall mortality rate has been reported to be as high as 20–40%. In addition, most patients had diabetes mellitus (DM) and obstructive uropathy. The most common isolated microorganism is Escherichia coli. This study aims to analyze the risk factors and performance of scoring systems in predicting the clinical outcomes of patients with EPN. Materials and Methods: We collected the data of patients with EPN in this single hospital-based retrospective study from the electronic medical records of Taichung Veterans General Hospital between January 2007 and December 2020. Radiological investigations of abdominal computed tomography (CT) confirmed the diagnosis of EPN. In addition, we analyzed demographics, clinical characteristics, and laboratory data. Finally, we used various scoring systems to predict clinical outcomes. Results: A total of fifty patients with EPN, whose diagnoses were confirmed through CT, were enrolled in the study. There were 18 males (36%) and 32 females (64%), with a mean age of 64.3 ± 11.3 years. The in-hospital mortality rate was 16%. A DM of 34 (68%) patients was the most common comorbidity. Fever was the most common symptom, found in 25 (50%) patients. The Mortality in Emergency Department Sepsis (MEDS) score was 4.64 ± 3.67 for survivors and 14.25 ± 5.34 for non-survivors (p < 0.001). The National Early Warning Score (NEWS) was 3.64 ± 2.33 for survivors and 7.13 ± 4.85 for non-survivors (p = 0.046). The Rapid Emergency Medicine Score (REMS) was 5.81 ± 1.97 for survivors and 9.13 ± 3.87 for non-survivors (p = 0.024). Regarding performance of mortality risk prediction, the AUC of ROC was 0.932 for MEDS, 0.747 for REMS, and 0.72 for NEWS. Conclusions: MEDS, REMS, and NEWS could be prognostic tools for the prediction of the clinical outcomes of patients with EPN. MEDS showed the best sound performance. In those with higher scores in MEDS (≥12), REMS (≥10), and NEWS (≥8), we recommended aggressive management and appropriate antimicrobial therapy as soon as possible to reduce mortality. Further large-scale studies are required to gain a deep understanding of this disease and to ensure patient safety.
The Impact of Late Follicular Phase Progesterone Elevation on Cumulative Live Birth Rate and Embryo Quality in 4072 Freeze-All Cycles
Authors: Huang Ling , Huang Sunxing , Wen Yangxing , Zhang Xiubing , Hu Xiaokun , Wu Rihan , Chen Minghui , Zhou Canquan
Published: December 2022

Late follicular phase progesterone elevation during in vitro fertilization impedes embryo implantation. It is unclear whether late follicular phase progesterone elevation still has a negative effect on cumulative live births and embryo quality when a freeze-all strategy is adopted. Data from a total of 4072 patients were reviewed. All patients used the freeze-all strategy. Multivariate regression analyses were used to assess the association of progesterone levels with both cumulative live birth and embryo quality. There was no significant difference in the cumulative live birth rate between the groups with progesterone level <1.5 ng/mL and ≥1.5 ng/mL. The progesterone level was not associated with cumulative live birth and embryo quality.
How Could Medical and Surgical Treatment Affect the Quality of Life in Glaucoma Patients? A Cross-Sectional Study
Authors: Pastore Marco Rocco , Milan Serena , Agolini Rossella , Egidi Leonardo , Agostini Tiziano , Belfanti Lorenzo , Cirigliano Gabriella , Tognetto Daniele
Published: December 2022

Background: To evaluate and compare the visual function and the quality of life (QoL) in glaucomatous patients treated with topical medical therapy (TMT) alone, canaloplasty (CP), or trabeculectomy (TB). Methods: A total of 291 eyes of 167 patients with primary open-angle glaucoma or secondary pseudoexfoliative glaucoma in TMT or surgically treated with CP or TB were included. Eligibility criteria for surgical patients included not needing TMT after surgery. Each patient underwent a visual field assessment and peripapillary retinal nerve fiber layer (pRNFL) optical coherence tomography and filled out the Glaucoma Symptoms Scale (GSS) questionnaire and the 25-Item National Eye Institute Visual Functioning Questionnaire (25-NEI-VFQ). Comparison between the QoL level of the three groups and its correlation with optic nerve’s anatomical and functional status was the primary outcome. Results: CP patients reported the best general vision (p = 0.01), a lower incidence of eye burning (p = 0.03), and the lowest annoyance level of non-visual symptoms (p = 0.006). QoL positively correlated with pRNFL thickness, whereas no correlation was found with visual field damage. Conclusion: CP provides a better QoL when compared both to TB and TMT, regardless of glaucoma stage. pRNFL seems to provide additional information for predicting change in QoL.
The Impact of a Very Short Abstinence Period on Conventional Sperm Parameters and Sperm DNA Fragmentation: A Systematic Review and Meta-Analysis
Authors: Barbagallo Federica , Cannarella Rossella , Crafa Andrea , Manna Claudio , La Vignera Sandro , Condorelli Rosita A. , Calogero Aldo E.
Published: December 2022

Purpose: In recent years, a growing number of studies have supported the beneficial effects of a very short abstinence period on sperm parameters, especially in patients with oligoasthenozoospermia. However, the results are controversial and no consensus exists regarding whether to request a second semen collection in clinical practice. Therefore, this systematic review and meta-analysis aimed to evaluate the influence of a very short abstinence period (within 4 h) on conventional sperm parameters and sperm DNA fragmentation (SDF) rate. Materials and Methods: The literature search was performed using Scopus and PubMed databases. The meta-analysis was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol (PRISMA-P) guidelines. All eligible studies were selected according to the Population, Intervention, Comparison/Comparator, Outcomes, and Study design (PICOS) model. The quality of evidence of the included studies was analyzed through the Cambridge Quality Checklists. The standardized mean difference (SMD) was used to analyze the outcomes. Cochran-Q and I2 statistics were used to evaluate statistical heterogeneity. Results: We assessed for eligibility 1334 abstracts, and 19 studies were finally included. All 19 articles evaluated the effects of a very short abstinence period on sperm parameters and, among these, 5 articles also evaluated the effects on SDF rate. The quantitative analysis showed a significant reduction in semen volume after a very short abstinence period in both normozoospermic men and patients with oligozoospermia, asthenozoospermia, and/or teratozoospermia (OAT) patients. We found a statistically significant increase in sperm concentration and total and progressive motility in the second ejaculation of patients with OAT. In contrast, the SDF rate decreased significantly in the second ejaculate of OAT patients. Conclusions: This is the first systematic review and meta-analysis investigating the impact of a very short abstinence period on sperm parameters and SDF rate. The results suggest that collecting a second consecutive ejaculation after a very short time from the first could represent a simple and useful strategy for obtaining better-quality spermatozoa, especially in patients with abnormal sperm parameters.
The Role of Stress in Stable Patients with Takotsubo Syndrome—Does the Trigger Matter?
Authors: Moady Gassan , Ali Otman , Sweid Rania , Atar Shaul
Published: December 2022

Background: Takotsubo syndrome (TTS) is a unique type of reversible cardiomyopathy that predominantly affects elderly women. The role of physical and emotional stress in the pathophysiology of TTS is well established. However, the association between preceding emotional triggers and clinical outcomes in stable patients has not yet been fully investigated. We aimed to investigate the association between emotional triggers before symptom onset and clinical outcomes in stable patients with TTS. Methods: This is a retrospective cohort study based on the data of patients with ICD-9 discharge diagnosis of TTS between 2017 and 2022. Patients were divided into two groups: with and without obvious emotional trigger before symptom onset. Demographic, laboratory, echocardiographic, and clinical outcomes were obtained and compared between the two groups. Results: We included 86 patients (93% were women, mean age 68.8 ± 12.3 years). Of them, 64 (74.4%) reported an emotional trigger before symptom onset. Patients with a previous emotional trigger had a longer hospital stay (4.3 + 2.0 days vs. 3.0 + 1.4, p = 0.002) with no difference in in-hospital complications (32.8% vs. 13.6%, p = 0.069), with no difference in 30-day mortality, readmissions, or recurrence rate between the groups. Conclusions: Patients with TTS related to an emotional trigger may represent a different population from patients without a preceding trigger by having more symptomatic disease and longer hospital stay, yet with no difference in the 30-day outcomes.
Bone Metastases from Gastric Cancer Resembling Paget’s Disease: A Case Report
Authors: Aiba Hisaki , Nakazato Tomoharu , Matsuo Hideo , Kimura Hiroaki , Saito Shiro , Sakai Takao , Murakami Hideki , Kawai Jun , Kawasaki Shingo , Imamura Yasuhiro
Published: December 2022

Systemic osteosclerotic lesions are frequently caused by multiple bone metastases or systemic metabolic disorders. However, bone metastasis from gastric cancer is rare. Herein, we describe such a case, with radiographic and clinical findings resembling Paget’s disease. The patient was an 80-year-old Japanese woman with a history of early gastric cancer, treated by partial gastrectomy 2 years prior. The patient sought medical care for chronic low back pain. On imaging, systemic sclerotic lesions were observed throughout the spine and pelvis, with an increase in bone mineral density from 0.86 g/cm3 (2 years prior) to 1.38g/cm3 (current visit) in the lumbar spine. Elevated serum levels of osteoblastic and osteolytic markers were identified. A bone biopsy was used to confirm the diagnosis of metastatic gastric cancer. The patient was treated with TS-1 and denosumab, with normalization of abnormal metabolic markers and alleviation of the back pain. Bone metastasis is reported in only 10% of cases of gastric cancer and, thus, is relatively rare. Therefore, our case of gastric cancer recurrence presenting with mixed osteoblastic and osteolytic bone lesions similar to Paget’s disease is relevant to the report. Bone biopsy is necessary for an accurate diagnosis.
Long-Term Surveillance and Management of Urological Complications in Chronic Spinal Cord-Injured Patients
Authors: Wu Shu-Yu , Jhang Jia-Fong , Liu Hsin-Ho , Chen Jian-Ting , Li Jian-Ri , Chiu Bin , Chen Sung-Lang , Kuo Hann-Chorng
Published: December 2022

Bladder dysfunction is a common complication after chronic spinal cord injury (SCI). Patients may experience renal function loss, urinary tract infection (UTI), urolithiasis, bladder cancer, and even life-threatening events such as severe sepsis or renal failure. Suitable patient care may prevent UTI and urinary incontinence, decrease medication use, and preserve renal function. As the primary goal is to preserve renal function, management should be focused on facilitating bladder drainage, the avoidance of UTI, and the maintenance of a low intravesical pressure for continence and complete bladder emptying. Currently, several bladder management options are available to SCI patients: (1) reflex voiding; (2) clean intermittent catheterization; (3) indwelling catheterization. The target organ may be the bladder or the bladder outlet. The purposes of intervention include the following: (1) increasing bladder capacity and/or decreasing intravesical pressure; (2) increasing bladder outlet resistance; (3) decreasing bladder outlet resistance; (4) producing detrusor contractility; (5) urinary diversion. Different bladder management methods and interventions may have different results depending on the patient’s lower urinary tract dysfunction. This review aims to report the current management options for long-term bladder dysfunction in chronic SCI patients. Furthermore, we summarize the most suitable care plans for improving the clinical outcome of SCI patients.
Acute Kidney Injury: Advances in Clinical Management
Authors: Lacquaniti Antonio , Monardo Paolo
Published: December 2022

Acute kidney injury (AKI), closely related to increased mortality, involved 15–20% of hospitalized patients with higher incidence, with about 50% in the intensive care unit (ICU) [...]
A Novel PiRNA Enhances CA19-9 Sensitivity for Pancreatic Cancer Identification by Liquid Biopsy
Authors: Li Weiyao , Gonzalez-Gonzalez Miguel , Sanz-Criado Lara , Garcia-Carbonero Nuria , Celdran Angel , Villarejo-Campos Pedro , Minguez Pablo , Pazo-Cid Roberto , Garcia-Jimenez Custodia , Orta-Ruiz Alberto , Garcia-Foncillas Jesus , Martinez-Useros Javier
Published: December 2022

Pancreatic cancer is one of the deadliest tumours worldwide, and its poor prognosis is due to an inability to detect the disease at the early stages, thereby creating an urgent need to develop non-invasive biomarkers. P-element–induced wimpy testis (PIWI) proteins work together with piwi-interacting RNAs (piRNAs) to perform epigenetic regulation and as such hold great potential as biomarkers for pancreatic cancer. PIWIL2 and PIWIL4 are associated with better prognosis, while PIWIL1 and PIWIL3 involvement appears to be associated with carcinogenesis. We aimed to discover PIWIL3- and PIWIL4-modulated piRNAs and determine their potential mechanisms in pancreatic cancer and the clinical implications. PIWIL3 or PIWIL4 was downregulated in pancreatic cancer-derived cell lines or in a non-tumour cell line. Differentially expressed piRNAs were analysed by next generation sequencing of small RNA. Nine fresh-frozen samples from solid human pancreases (three healthy pancreases, three intraductal papillary mucinous neoplasms, and three early-stage pancreatic cancers) were included in the sequencing analysis. Two piRNAs associated with PIWIL3 (piR-168112 and piR-162725) were identified in the neoplastic cells; in untransformed samples, we identified one piRNA associated with PIWIL4 (pir-366845). After validation in pancreatic cancer-derived cell lines and one untransformed pancreatic cell line, these piRNAs were evaluated in plasma samples from healthy donors (n = 27) or patients with pancreatic cancer (n = 45). Interestingly, piR-162725 expression identified pancreatic cancer patients versus healthy donors in liquid biopsies. Moreover, the potential of the serum carbohydrate antigen 19-9 (CA19-9) biomarker to identify pancreatic cancer patients was greatly enhanced when combined with piR-162725 detection. The enhanced diagnostic potential for the early detection of pancreatic cancer in liquid biopsies of these new small non-coding RNAs will likely improve the prognosis and management of this deadly cancer.
Inflammaging and Blood Pressure Profiles in Late Life: The Screening for CKD among Older People across Europe (SCOPE) Study
Authors: Tap Lisanne , Corsonello Andrea , Di Rosa Mirko , Fabbietti Paolo , Formiga Francesc , Moreno-González Rafael , Ärnlöv Johan , Carlsson Axel C. , Polinder-Bos Harmke A. , Roller-Wirnsberger Regina E. , Wirnsberger Gerhard H. , Kostka Tomasz , Guligowska Agnieszka , Artzi-Medvedik Rada , Yehoshua Ilan , Weingart Christian , Sieber Cornel C. , Gil Pedro , Lainez Martinez Sara , Lattanzio Fabrizia , Mattace-Raso Francesco U. S.
Published: December 2022

The neutrophil-to-lymphocyte ratio (NLR) is a marker for systemic inflammation. Since inflammation plays a relevant role in vascular aging, the aim of this study was to investigate whether NLR is associated with blood pressure profiles in older adults. This study was performed within the framework of the SCOPE study including 2461 outpatients aged 75 years and over. Mean blood pressure values, namely systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse pressure (PP) were investigated across tertiles of NLR. Change in blood pressure levels in 2 years of follow-up were compared across categories of baseline NLR. Data of 2397 individuals were used, of which 1854 individuals had hypertension. Mean values of blood pressure did not differ across categories of baseline NLR in individuals without hypertension. Individuals with hypertension with a high-range NLR had lower SBP and PP when compared to those in low-range NLR (mean difference SBP −2.94 mmHg, p = 0.032 and PP −2.55 mmHg, p = 0.030). Mean change in blood pressure in 2 years did only slightly differ in non-clinically relevant ranges, when compared across tertiles of baseline NLR. NLR as a marker of inflammaging was not associated with unfavorable blood pressure profiles in older individuals with or without hypertension.
Genetic Factors Causing Thyroid Dyshormonogenesis as the Major Etiologies for Primary Congenital Hypothyroidism: Clinical and Genetic Characterization of 33 Patients
Authors: Liu Rui , Tian Jing-Li , Huang Xiao-Ling , Song Yuan-Zong
Published: December 2022

Background and aims: Although the significance of primary congenital hypothyroidism (CH) is supported by an increasing amount of evidence, the clinical and genetic characteristics of this condition are still poorly understood. This study aimed to explore the underlying genetic etiologies in a cohort of primary CH patients. Subjects and Methods: The clinical data of 33 patients with primary CH were collected and analyzed via a cross-sectional study. Genetic analysis was performed by high-throughput sequencing and Sanger verification, and the pathogenicity of the novel missense variants was predicted using a variety of comprehensive bioinformatic tools. Results: Among the 33 patients, 22 (22/33, 66.7%) harbored pathogenic variants in the causative genes of thyroid dysgenesis or dyshormonogenesis, with DUOX2 (15/33, 45.5%) topping the list, followed by TG, TPO, DUOXA2 and PAX8. Four novel genetic variants were detected, including a pathogenic frameshift and three likely pathogenic missense variants. Positive neonatal screening for TSH, neonatal jaundice and abnormal thyroid morphology were the main positive findings among all cases. Although 31 of the total 33 CH patients exhibited normal anthropometric and social performance, the other 2 had poor prognosis in this study. Conclusions: This study reported 33 new CH patients bearing four novel genetic variants, which enriched the variant spectrum of CH genes. In this cohort, genetic factors causing thyroid dyshormonogenesis were the main etiologies of CH development. Most patients exhibited a favorable prognosis; however, systematic management remains a challenge in achieving improved clinical outcomes for CH patients.
Age, Sex and Previous Comorbidities as Risk Factors Not Associated with SARS-CoV-2 Infection for Long COVID-19: A Systematic Review and Meta-Analysis
Authors: Notarte Kin Israel , de Oliveira Maria Helena Santos , Peligro Princess Juneire , Velasco Jacqueline Veronica , Macaranas Imee , Ver Abbygail Therese , Pangilinan Flos Carmeli , Pastrana Adriel , Goldrich Nathaniel , Kavteladze David , Gellaco Ma. Margarita Leticia , Liu Jin , Lippi Giuseppe , Henry Brandon Michael , Fernández-de-las-Peñas César
Published: December 2022

Identification of predictors of long COVID-19 is essential for managing healthcare plans of patients. This systematic literature review and meta-analysis aimed to identify risk factors not associated with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, but rather potentially predictive of the development of long COVID-19. MEDLINE, CINAHL, PubMed, EMBASE, and Web of Science databases, as well as medRxiv and bioRxiv preprint servers were screened through 15 September 2022. Peer-reviewed studies or preprints evaluating potential pre-SARS-CoV-2 infection risk factors for the development of long-lasting symptoms were included. The methodological quality was assessed using the Quality in Prognosis Studies (QUIPSs) tool. Random-effects meta-analyses with calculation of odds ratio (OR) were performed in those risk factors where a homogenous long COVID-19 definition was used. From 1978 studies identified, 37 peer-reviewed studies and one preprint were included. Eighteen articles evaluated age, sixteen articles evaluated sex, and twelve evaluated medical comorbidities as risk factors of long COVID-19. Overall, single studies reported that old age seems to be associated with long COVID-19 symptoms (n = 18); however, the meta-analysis did not reveal an association between old age and long COVID-19 (n = 3; OR 0.86, 95% CI 0.73 to 1.03, p = 0.17). Similarly, single studies revealed that female sex was associated with long COVID-19 symptoms (n = 16); which was confirmed in the meta-analysis (n = 7; OR 1.48, 95% CI 1.17 to 1.86, p = 0.01). Finally, medical comorbidities such as pulmonary disease (n = 4), diabetes (n = 1), obesity (n = 6), and organ transplantation (n = 1) were also identified as potential risk factors for long COVID-19. The risk of bias of most studies (71%, n = 27/38) was moderate or high. In conclusion, pooled evidence did not support an association between advancing age and long COVID-19 but supported that female sex is a risk factor for long COVID-19. Long COVID-19 was also associated with some previous medical comorbidities.
Effectiveness of Different Rituximab Doses Combined with Leflunomide in the Treatment or Retreatment of Rheumatoid Arthritis: Part 2 of a Randomized, Placebo-Controlled, Investigator-Initiated Clinical Trial (AMARA)
Authors: Koehm Michaela , Foldenauer Ann C. , Rossmanith Tanja , Alten Rieke , Aringer Martin , Backhaus Marina , Burmester Gerd R. , Feist Eugen , Kellner Herbert , Krueger Klaus , Müller-Ladner Ulf , Rubbert-Roth Andrea , Tony Hans-Peter , Wassenberg Siegfried , Burkhardt Harald , Behrens Frank
Published: December 2022

Background: The optimal dose of rituximab in combination with leflunomide in patients with rheumatoid arthritis (RA) is not known. Methods: In Part 1 (previously reported) of the investigator-initiated AMARA study (EudraCT 2009-015950-39; ClinicalTrials.gov NCT01244958), improvements at week (W)24 were observed in patients randomized to rituximab + leflunomide compared with placebo + leflunomide. In the study reported here (Part 2), Part 1 responders received rituximab 500 or 1000 mg at W24/26 plus ongoing leflunomide. Patients were randomized at baseline to their eventual W24 treatment group. The Part 2 primary outcome was the mean Disease Activity Score-28 joints (DAS28) at W52, based on the last observation carried forward (LOCF) analyses and a two-sided analysis of variance. Patient-reported outcomes (PROs) and adverse events were evaluated. Results: Eighty-three patients received rituximab at W24/26 (31 rituximab→rituximab 1000 mg; 29 rituximab→rituximab 500 mg; 10 placebo→rituximab 1000 mg; 13 placebo→rituximab 500 mg). At W52, there were no significant differences in DAS28 between rituximab doses in patients originally treated with rituximab or those originally treated with placebo. In the Part 1 placebo group, the higher rituximab dose was associated with greater improvements in ACR response rates and some PROs. Adverse events were similar regardless of rituximab dose. Conclusions: Retreatment with rituximab 500 mg and 1000 mg showed comparable efficacy, whereas an initial dose of rituximab 500 mg was associated with lower response rates versus 1000 mg. Reduced treatment response with the lower dose in patients initially treated with placebo may have been influenced by small numbers and baseline disease activity.
Psychological Profile and Social Behaviors of Patients with Hyperacusis
Authors: Sacchetto Luca , Apa Enrico , Ciorba Andrea , Palma Silvia , Caragli Valeria , Gherpelli Chiara , Monzani Daniele , Genovese Elisabetta , Nocini Riccardo
Published: December 2022

Increased noise sensitivity refers to the abnormal subjective response to external sounds, with a prevalence of between 8% and 15.2% in the adult population as suggested by epidemiological studies. The basic neural mechanism of hyperacusis still remains obscure, so therapies for this often-devastating symptom remain elusive. The aim of this study was to assess psychological profiles in patients with presbycusis without tinnitus in a perspective case-control design. All subjects were initially submitted to audiological evaluation (tympanometry, recordings of the acoustic reflex thresholds, pure tone audiometry) and subsequently were administered the following questionnaires: the hyperacusis questionnaire (HQ), the brief symptom inventory (BSI), and the modified somatic perception questionnaire (MSPQ). Patients with hyperacusis reported a total score and subscales (attentional, social, and emotional) of the HQ significantly higher than controls. They also reported higher scores of the MSPQ and significantly higher mean values with concern to the somatization, obsessive-compulsive, interpersonal sensitivity, depression, and anxiety subscales of the BSI. These results show that psychological distress, as expressed by higher level of somatic attention, somatization, anxiety, and depression, is a significant factor to consider for a complete diagnosis and effective treatment of hyperacusis. For a correct diagnosis of patients seeking help for hyperacusis, their psychological distress should also be assessed, regardless of their hearing abilities. Further studies are required to investigate the pathological mechanisms that are involved in the onset of hyperacusis in patients with normal hearing and those with sensorineural hearing loss.
Effects of Rifaximin on Circulating Albumin Structures and Serum Ammonia Levels in Patients with Liver Cirrhosis: A Preliminary Study
Authors: Miwa Takao , Hanai Tatsunori , Imai Kenji , Takai Koji , Shiraki Makoto , Hayashi Hideki , Shimizu Shogo , Nishigaki Yoichi , Tomita Eiichi , Shimizu Masahito
Published: December 2022

Circulating albumin structures, including their oxidized and reduced forms, are involved in hepatic encephalopathy (HE) development. However, the effects of rifaximin, a key drug in HE treatment, on the circulating albumin structure in patients with liver cirrhosis remain unclear. In this multicenter prospective study, eight patients with hyperammonemia (≥80 μg/dL) were enrolled. The circulating albumin structure was evaluated using the ratio of oxidized albumin (human nonmercaptalbumin, HNA). Patients were administered 400 mg rifaximin 3 times/day for 3 months, and laboratory data were assessed at baseline and during observation. Among the eight patients, three were men; the median age and body mass index were 70 years and 26.4 kg/m2, respectively. The median HNA and serum ammonia levels at baseline were 41% and 143 μg/dL, respectively. After rifaximin therapy, HNA showed a decreasing tendency (median; from 41% to 36%, p = 0.321), but serum albumin levels showed no significant change (from 3.5 g/dL to 3.5 g/dL, p = 1.00); serum ammonia levels significantly reduced (median: 143 μg/dL to 76 μg/dL, p = 0.015). Thus, rifaximin reduces serum ammonia levels and may improve circulating albumin structure in patients with cirrhosis. Further large-scale studies are required to confirm these preliminary results.
Carbonaceous Nanocomposites for Biomedical Applications as High-Drug Loading Nanocarriers for Sustained Delivery: A Review
Authors: Sun Bo , Wang Weijun , Sain Mohini
Published: December 2022

Low drug loading and high initial burst release are common drawbacks for most polymeric nanocarriers in their biomedical applications. This review emphasizes the use of unconventional carbonaceous nanocomposites as functional carriers to improve the drug loading capacity and their capability of protecting drugs from the surrounding environment. The unique properties of typical carbonaceous nanocarriers, including nanotube, graphene/graphite, fullerene, and nanodiamonds/diamond-like carbon, are presented. Advanced methods for the surface functionalization of carbonaceous nanocarriers are described, followed by a summary of the most appealing demonstrations for their efficient drug loading and sustained release in vitro or in vivo. The fundamental drug delivery concepts based on controlling mechanisms, such as targeting and stimulation with pH, chemical interactions, and photothermal induction, are discussed. Additionally, the challenges involved in the full utilization of carbonaceous nanocomposites are described, along with the future perspectives of their use for enhanced drug delivery. Finally, despite its recent emergence as a drug carrier, carbon-based nanocellulose has been viewed as another promising candidate. Its structural geometry and unique application in the biomedical field are particularly discussed. This paper, for the first time, taxonomizes nanocellulose as a carbon-based carrier and compares its drug delivery capacities with other nanocarbons. The outcome of this review is expected to open up new horizons of carbonaceous nanocomposites to inspire broader interests across multiple disciplines.
Progress of Electrospun Nanofibrous Carriers for Modifications to Drug Release Profiles
Authors: Wang Ying , Yu Deng-Guang , Liu Yang , Liu Ya-Nan
Published: December 2022

Electrospinning is an advanced technology for the preparation of drug-carrying nanofibers that has demonstrated great advantages in the biomedical field. Electrospun nanofiber membranes are widely used in the field of drug administration due to their advantages such as their large specific surface area and similarity to the extracellular matrix. Different electrospinning technologies can be used to prepare nanofibers of different structures, such as those with a monolithic structure, a core–shell structure, a Janus structure, or a porous structure. It is also possible to prepare nanofibers with different controlled-release functions, such as sustained release, delayed release, biphasic release, and targeted release. This paper elaborates on the preparation of drug-loaded nanofibers using various electrospinning technologies and concludes the mechanisms behind the controlled release of drugs.
Detecting Audio Adversarial Examples in Automatic Speech Recognition Systems Using Decision Boundary Patterns
Authors: Zong Wei , Chow Yang-Wai , Susilo Willy , Kim Jongkil , Le Ngoc Thuy
Published: December 2022

Automatic Speech Recognition (ASR) systems are ubiquitous in various commercial applications. These systems typically rely on machine learning techniques for transcribing voice commands into text for further processing. Despite their success in many applications, audio Adversarial Examples (AEs) have emerged as a major security threat to ASR systems. This is because audio AEs are able to fool ASR models into producing incorrect results. While researchers have investigated methods for defending against audio AEs, the intrinsic properties of AEs and benign audio are not well studied. The work in this paper shows that the machine learning decision boundary patterns around audio AEs and benign audio are fundamentally different. Using dimensionality-reduction techniques, this work shows that these different patterns can be visually distinguished in two-dimensional (2D) space. This in turn allows for the detection of audio AEs using anomal- detection methods.
3D Flooding Maps as Response to Tsunami Events: Applications in the Central Sicilian Channel (Southern Italy)
Authors: Distefano Salvatore , Baldassini Niccolò , Barbagallo Viviana , Borzì Laura , D’Andrea Natale Maria , Urso Salvatore , Di Stefano Agata
Published: December 2022

The assessment of the vulnerability of a site to tsunami events should take into consideration the geomorphological setting, which is strongly determined by the stratigraphic framework of the area. Lampedusa island is located in the central portion of the Sicilian Channel (Mediterranean Sea, Italy), where a significant incidence of tsunamis (with wave runup above 15 m) caused by earthquakes and submarine landslides has been historically documented. This work shows the geomorphological and stratigraphic differences between the western and south-eastern sectors of Lampedusa island. This update to the geological characterization of the island was used to create 3D flooding maps according to runup steps of 5 m, 10 m, and 15 m, thus showing a homogeneous involvement of the south-eastern sector of Lampedusa. Furthermore, our study aims to provide a geomorphological-stratigraphic base for a mathematical-statistical model to create coastal flooding maps due to tsunami waves. As such, this tool is useful for evaluation of strategic infrastructure for the security of the island and the improvement of risk management in civil protection.
Cell Immobilization for Erythritol Production
Authors: Hijosa-Valsero María , Paniagua-García Ana I. , Díez-Antolínez Rebeca
Published: December 2022

Nowadays, commercial erythritol synthesis is performed by free-cell fermentation with fungi in liquid media containing high concentrations of pure carbon sources. Alternative fermentation techniques, such as cell immobilization, could imply an economic and energetic improvement for erythritol-producing factories. The present work describes, for the first time, the feasibility of achieving cell immobilization during erythritol production. Cells of the fungus Moniliella pollinis were successfully immobilized on a cotton cloth which was placed inside a 2-L bioreactor, where they were fed with red grape must supplemented with yeast extract. They produced 47.03 ± 6.16 g/L erythritol in 96 h (yield 0.18 ± 0.04 g/g) over four consecutive fermentation batches. The immobilized cells remained stable and operative during a 456 h period. The erythritol concentration attained was similar (p > 0.05; Tukey HSD test) to the reference value obtained with the use of free cells (41.88 ± 5.18 g/L erythritol) under the same fermentation conditions. The comparable results observed for free and immobilized cells evidences the efficiency of the immobilization system. Therefore, the proposed method for erythritol bioproduction eliminates the need for the continuous preparation of fungal inocula before each fermentation batch, thus reducing the costs of the reagents and energy.
The Calcium Chloride Responsive Type 2C Protein Phosphatases Play Synergistic Roles in Regulating MAPK Pathways in Magnaporthe oryzae
Authors: Anjago Wilfred M. , Biregeya Jules , Shi Mingyue , Chen Yixiao , Wang Yupeng , Wang Zonghua , Hong Yonghe , Chen Meilian
Published: December 2022

Reversible protein phosphorylation is essential in cellular signal transduction. The rice blast fungus Magnaporthe oryzae contains six putative type 2C protein phosphatases, namely MoPtc1, MoPtc2, MoPtc5, MoPtc6, MoPtc7, and MoPtc8. The major functions of MoPtc1 and MoPtc2 have been reported recently. In this communication, we found that MoPtc1 and MoPtc2 were induced by calcium chloride. We also found that the deletion of both MoPtc1 and MoPtc2 resulted in the overstimulation of both the high-osmolarity glycerol (Hog1) and pathogenicity MAP kinase 1 (Pmk1) pathways in M. oryzae. MoPtc1 was recruited directly to Osm1 (the osmotic stress-sensitive mutant) by the adaptor protein MoNbp2 to inactivate the Osm1 during hypoosmotic stress, distinct from the budding yeast. Moreover, we showed that MoPtc1 and MoPtc2 were localized in different cellular compartments in the fungal development. Taken together, we added some new findings of type 2C protein phosphatases MoPtc1 and MoPtc2 functions to the current knowledge on the regulation of MAPK signaling pathways in M. oryzae.
Eumycetoma Caused by Madurella pseudomycetomatis in a Captive Tiger (Panthera tigris)
Authors: Orlandi Margherita , Giglia Giuseppe , Danesi Patrizia , Laricchiuta Piero , Abramo Francesca
Published: December 2022

A captive-kept adult male tiger presented with a large cutaneous and subcutaneous mass on the thigh with a fistula. During sedation, multiple nodules were detected and samples for a histopathological exam were collected. Histologically, granulomatous panniculitis and dermatitis were seen around dense aggregates of pigmented fungal hyphae, and a diagnosis of phaeohyphomycosis was made; considering the clinical features, it was classified as a eumycotic mycetoma. This is a rarely reported subcutaneous fungal infection in humans and animals, caused by dematiaceous fungi. Clinically, it is characterized by tumefaction, fistulous sinus tracts, and the formation of macroscopically visible grains. In the literature, only a few infections in wild felids have been reported. In this case, Fontana–Masson staining better showed pigmentation and panfungal PCR and sequencing identified Madurella pseudomyectomatis (OP623507) as the causative agent. Systemic therapy with oral administration of itraconazole was planned, but the patient died during the first period of treatment. The animal was not submitted for post-mortem examination. Visceral dissemination of the agent cannot be excluded. To the authors’ knowledge, this is the first report of eumycotic mycetoma by Madurella pseudomycetomatis in a captive tiger.
Prediction of Cervical Cancer Outcome by Identifying and Validating a NAD+ Metabolism-Derived Gene Signature
Authors: Chen Aozheng , Jing Wanling , Qiu Jin , Zhang Runjie
Published: December 2022

Cervical cancer (CC) is the second most common female cancer. Excellent clinical outcomes have been achieved with current screening tests and medical treatments in the early stages, while the advanced stage has a poor prognosis. Nicotinamide adenine dinucleotide (NAD+) metabolism is implicated in cancer development and has been enhanced as a new therapeutic concept for cancer treatment. This study set out to identify an NAD+ metabolic-related gene signature for the prospect of cervical cancer survival and prognosis. Tissue profiles and clinical characteristics of 293 cervical cancer patients and normal tissues were downloaded from The Cancer Genome Atlas database to obtain NAD+ metabolic-related genes. Based on the differentially expressed NAD+ metabolic-related genes, cervical cancer patients were divided into two subgroups (Clusters 1 and 2) using consensus clustering. In total, 1404 differential genes were acquired from the clinical data of these two subgroups. From the NAD+ metabolic-related genes, 21 candidate NAD+ metabolic-related genes (ADAMTS10, ANGPTL5, APCDD1L, CCDC85A, CGREF1, CHRDL2, CRP, DENND5B, EFS, FGF8, P4HA3, PCDH20, PCDHAC2, RASGRF2, S100P, SLC19A3, SLC6A14, TESC, TFPI, TNMD, ZNF229) were considered independent indicators of cervical cancer prognosis through univariate and multivariate Cox regression analyses. The 21-gene signature was significantly different between the low- and high-risk groups in the training and validation datasets. Our work revealed the promising clinical prediction value of NAD+ metabolic-related genes in cervical cancer.
The Soluble Folate Receptor in Autism Spectrum Disorder: Relation to Autism Severity and Leucovorin Treatment
Authors: Frye Richard E. , Lane Alison , Worner Ashley , Werner Brianna A. , McCarty Patrick J. , Scheck Adrienne C. , Collins Heidi L. , Adelman Steven J. , Quadros Edward V. , Rossignol Daniel A.
Published: December 2022

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder with life-long consequences that affects up to 1 in 44 children. Treatment with leucovorin (folinic acid), a reduced form of folate, has been shown to improve symptoms in those with ASD and folate pathway abnormalities in controlled clinical trials. Although soluble folate binding proteins (sFBPs) have been observed in the serum of some patients with ASD, the significance of this finding has not been studied. Here, we present a cohort of ASD patients with sFBPs. These patients had severe ASD and were medically complex. Using baseline controlled open-label methodology and standardized assessments, these patients were found to improve in both core and associated ASD symptoms with leucovorin treatment. No adverse effects were related to leucovorin treatment. This is the first report of the sFBPs in ASD. This study complements ongoing controlled clinical trials and suggests that leucovorin may be effective for children with ASD who are positive for sFBPs. Further, sFBPs might be important biomarkers for treatment response to leucovorin in children with ASD. This study paves the way for further controlled studies for patients with sFBPs.
Correction: Hasegawa et al. Impacts of Interaction of Mental Condition and Quality of Life between Donors and Recipients at Decision-Making of Preemptive and Post-Dialysis Living-Donor Kidney Transplantation. J. Pers. Med. 2021, 11, 414
Authors: Hasegawa Toshiki , Nishikawa Kouhei , Tamura Yuko , Oka Tomoka , Urawa Aiko , Watanabe Saori , Mizuno Shugo , Okada Motohiro
Published: December 2022

The authors wish to make the following corrections to this paper [...]
mHealth App Barriers, Usability, and Personalization: A Cross-Sectional Study from Egypt and Saudi Arabia
Authors: Arafa Ahmed , Mostafa Zahraa M. , Sheerah Haytham A. , Alzahrani Fahad , Almuzaini Yasir , Senosy Shaimaa , Hassan Radwa Ibrahim Ali
Published: December 2022

Mobile health (mHealth) has emerged as a substantial segment of eHealth. Herein, we conducted a cross-sectional study to investigate mHealth app barriers, usability, and personalization in Egypt and Saudi Arabia. We used a Google survey to recruit participants from both countries between the 15th of September and the 15th of October 2022. Among 299 participants (247 from Egypt and 52 from Saudi Arabia), aged ≥ 18 years, 27.4% reported mHealth app use. In the age-, sex-, and country-adjusted regression models, age > 25 years: OR (95% CI) = 1.98 (1.11, 3.54), residing in Saudi Arabia: OR (95% CI) = 4.33 (2.22, 8.48), and physical activity: OR (95% CI) = 2.53 (1.44, 4.44) were associated with mHealth app use. The main mHealth app purposes were lifestyle promotion (35.4%), diet and nutrition (30.5%), and administrative services (13.4%). On a scale from 20 to 100, mHealth app usability scores were 46.3% (20–40), 7.3% (41–60), 31.7% (61–80), and 14.7% (81–100). According to 93.9% of users, mHealth app features were modifiable to meet personal health goals, while 37% stated that mHealth apps helped them set new personal health goals. In conclusion, age, residing in Saudi Arabia (compared to Egypt), and physical activity were positively associated with mHealth app use. mHealth app feature personalization and helping users set new personal health goals were largely reported, suggesting that mHealth has the potential to help put personalized healthcare into practice.
Fog Computing, Cloud Computing and IoT Environment: Advanced Broker Management System
Authors: Al Masarweh Mohammed , Alwada’n Tariq , Afandi Waleed
Published: December 2022

Cloud computing is a massive amount of dynamic ad distributed resources that are delivered on request to clients over the Internet. Typical centralized cloud computing models may have difficulty dealing with challenges caused by IoT applications, such as network failure, latency, and capacity constraints. One of the introduced methods to solve these challenges is fog computing which makes the cloud closer to IoT devices. A system for dynamic congestion management brokerage is presented in this paper. With this proposed system, the IoT quality of service (QoS) requirements as defined by the service-level agreement (SLA) can be met as the massive amount of cloud requests come from the fog broker layer. In addition, a forwarding policy is introduced which helps the cloud service broker to select and forward the high-priority requests to the appropriate cloud resources from fog brokers and cloud users. This proposed idea is influenced by the weighted fair queuing (WFQ) Cisco queuing mechanism to simplify the management and control of the congestion that may possibly take place at the cloud service broker side. The system proposed in this paper is evaluated using iFogSim and CloudSim tools, and the results demonstrate that it improves IoT (QoS) compliance, while also avoiding cloud SLA violations.
Spatio-Temporal Distribution and Driving Factors of Ecosystem Service Value in a Fragile Hilly Area of North China
Authors: Gao Fengjie , Cui Jinfang , Zhang Si , Xin Xiaohui , Zhang Shaoliang , Zhou Jun , Zhang Ying
Published: December 2022

Ecosystem services (ESs) are essential for human society, and maintaining harmony between ecosystems and humanity to mitigate ES degradation is the fundamental basis for achieving a sustainable state. However, due to the influence of land use and land cover (LULC) and other ecological-economic factors, the quality and capacity of ESs supporting human welfare continue to decline, and the specific processes involved in this decline are still unclear. In this paper, a dynamically reconstructed assessment model was designed based on the equivalent factor method to estimate the Ecosystem service value (ESV) and to reveal its spatiotemporal response to LULC in a hilly area located in the Economic Circle of Beijing-Tianjin-Hebei during the period from 2000 to 2020; the structural equation model was also used to detect the detailed contribution of ecological-economic factors on ESV. Results showed that due to the decrease in forest land and the sprawl of orchard and construction land between 2000 and 2020, the spatial richness of various ecosystem services reduced, resulting in a decline in the total value of regional ecosystem services. The interaction of LULC, ecological and economic factors increased the regional heterogeneity of ESV. LULC caused a significantly direct impact on ESV (0.543), while economic factors had a negative direct impact on ESV (−0.26). Moreover, terrain factors affected the ESV through LULC and meteorological factors (0.259). The results of this study enrich our understanding of the detailed spatiotemporal variation and driving factors underlying the diminishing ESV in a rapidly developing hilly area, which has substantial guiding implications for land planning and ecosystem protection policies.