bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical exome-based panel testing for medically actionable secondary findings in a cohort of 383 Italian participants
Authors: Martone Stefania , Buonagura Autilia Tommasina , Marra Roberta , Rosato Barbara Eleni , Del Giudice Federica , Bonfiglio Ferdinando , Capasso Mario , Iolascon Achille , Andolfo Immacolata , Russo Roberta 
Published: November 2022

Background: Next-generation sequencing-based genetic testing represents a great opportunity to identify hereditary predispositions to specific pathological conditions and to promptly implement health surveillance or therapeutic protocols in case of disease. The term secondary finding refers to the active search for causative variants in genes associated with medically actionable conditions.Methods: We evaluated 59 medically actionable ACMG genes using a targeted in silico analysis of clinical exome sequencing performed in 383 consecutive individuals referred to our Medical Genetics Unit. A three-tier classification system of SFs for assessing their clinical impact and supporting a decision-making process for reporting was established.Results: We identified SFs with high/moderate evidence of pathogenicity in 7.0% (27/383) of analyzed subjects. Among these, 12/27 (44.4%) were carriers of a high-risk recessive disease allele. The most represented disease domains were cancer predisposition (33.3%), cardiac disorders (16.7%), and familial hypercholesterolemia (12.5%).Conclusion: Although still debated, ensuring during NGS-based genetic testing an opportunistic screening might be valuable for personal and familial early management and surveillance of medically actionable disorders, the individual’s reproductive choices, and the prevalence assessment of underestimated hereditary genetic diseases.
Ovarian cancer stem cells: Critical roles in anti-tumor immunity
Authors: Ding Jing , Zhang Yan , Che Yan 
Published: November 2022

Ovarian cancer is a significant cause of cancer-related mortality in women. Over the past 3 decades, there has been a high incidence of recurrent chemoresistant disease, despite the relative effectiveness of current treatment strategies. This is partly attributed to cancer stem cells (CSC), a subpopulation that has acquired stem cell properties that allow these cells to evade standard chemotherapy and cause disease recurrence. Therefore, there is an urgent need for basic knowledge about CSC to develop innovative therapeutic approaches for ovarian cancer. These CSC subpopulations have been identified in ovarian cancer cell lines, tumors or ascites, and findings suggest that ovarian CSCs may be as heterogeneous as the disease itself. CSCs regulate the phenotype and function of immune cells involved in antitumor immunity, so a better understanding of the signaling pathways that interact between CSCs, immune cells and tumor cells will pave the way for the clinical application of CS in cancer immunotherapy. This review will focus on the markers currently used to identify and isolate these cells summarize current knowledge on the molecular and cellular mechanisms responsible for CSC-dependent regulation of antitumor immune responses. We will discuss the signaling pathways involved in CSC survival, replication, and differentiation as well as potential therapeutic targeting strategies.
Health professionals' perspectives on clinical challenges in managing hypertensive disorders of pregnancy and recommendations for improving care: A multi-center qualitative study
Authors: Adu-Bonsaffoh Kwame , Tamma Evelyn , Nwameme Adanna Uloaku , Browne Joyce L. 
Published: November 2022

BackgroundHypertensive disorders of pregnancy (HDP) are a leading cause of maternal mortality and morbidity globally despite the intensive international effort to improving maternal care. Substandard clinical care has emerged as a major contributing factor to the high maternal deaths associated with maternal hypertension globally and the impact is severer in low- and middle-income countries (LMICs). Context specific challenges impact negatively on the quality of maternity care and health providers play a crucial role in achieving positive pregnancy experiences for women. This study explored the perspectives of health professionals on the clinical challenges associated with the management of HDP in Ghana and recommendations for improving care.MethodsA multi-center qualitative study using in-depth interviews (IDIs) was conducted in five major hospitals in the Greater Accra Region of Ghana between June 2018 and March 2019. Health professionals (midwives/nurses and medical doctors) who have worked at the study sites for at least three months were included. Data were analysed based on thematic content using Nvivo software.ResultsWe included 62 health professionals comprising 40 midwives/nurses (64.5%) with a median age of 32.5 years (range 26 to 59) and 22 medical doctors (34.5%) with a median age of 34 years (range 25 to 55). Health providers highlighted major challenges associated with clinical management of hypertension in pregnancy: (1) patient-related factors (inadequate understanding and misconceptions about hypertension in pregnancy, women's non-compliance with clinical advice, financial constraints); (2) health system-related challenges (frequent unavailability of logistics, medications and laboratory support, delays in provision of care and limitations in the health insurance coverage); (3) health provider associated factors (inadequate number of health professionals and poor attitudes). Context-specific recommendations suggested for improving the quality of care in managing maternal hypertension include restructuring of the health system to reduce delays in providing care, improving financial coverage of medical insurance, encouraging social/family support, enhancing education on HDP and strengthening the health workers’ numbers and working conditions.ConclusionMajor challenges in the clinical management of HDP relate to the health system, health professionals and pregnant women themselves. Context-specific interventions are required to improve the quality of care for hypertensive mothers including regular health education, re-structuring of the health systems, refresher courses for health providers, improvement in health insurance coverage and government subsidy for hypertensive women.
A subtractive proteomics approach for the identification of immunodominant Acinetobacter baumannii vaccine candidate proteins
Authors: Acar Mustafa Burak , Ayaz-Güner Şerife , Güner Hüseyin , Dinç Gökçen , Ulu Kılıç Ayşegül , Doğanay Mehmet , Özcan Servet 
Published: November 2022

BackgroundAcinetobacter baumannii is one of the most life-threatening multidrug-resistant pathogens worldwide. Currently, 50%–70% of clinical isolates of A. baumannii are extensively drug-resistant, and available antibiotic options against A. baumannii infections are limited. There is still a need to discover specific de facto bacterial antigenic proteins that could be effective vaccine candidates in human infection. With the growth of research in recent years, several candidate molecules have been identified for vaccine development. So far, no public health authorities have approved vaccines against A. baumannii.MethodsThis study aimed to identify immunodominant vaccine candidate proteins that can be immunoprecipitated specifically with patients’ IgGs, relying on the hypothesis that the infected person’s IgGs can capture immunodominant bacterial proteins. Herein, the outer-membrane and secreted proteins of sensitive and drug-resistant A. baumannii were captured using IgGs obtained from patient and healthy control sera and identified by Liquid Chromatography- Tandem Mass Spectrometry (LC-MS/MS) analysis.ResultsUsing the subtractive proteomic approach, we determined 34 unique proteins captured only in drug-resistant A. baumannii strain via patient sera. After extensively evaluating the predicted epitope regions, solubility, transverse membrane characteristics, and structural properties, we selected several notable vaccine candidates.ConclusionWe identified vaccine candidate proteins that triggered a de facto response of the human immune system against the antibiotic-resistant A. baumannii. Precipitation of bacterial proteins via patient immunoglobulins was a novel approach to identifying the proteins that could trigger a response in the patient immune system.
Toxicity profile of combined immune checkpoint inhibitors and thoracic radiotherapy in esophageal cancer: A meta-analysis and systematic review
Authors: Xu Tongzhen , Liu Yunsong , Lu Xiaotong , Liang Jun 
Published: November 2022

BackgroundTherapies based on the combination of immune checkpoint inhibitors (ICIs) and thoracic radiotherapy (TRT) are transforming the treatment landscape of esophageal cancer. Nevertheless, the available data on adverse events (AEs) mainly stemmed from several prospective clinical trials and retrospective studies, in which, AE data are often handled and reported with less rigor than the primary beneficial outcomes of the study. Thus, we conducted a systematic review to investigate the toxicity spectrum of these novel regimens.MethodWe searched for all prospective clinical trials investigating the role of ICIs combined with TRT published between January 2010 and August 2022. Study articles and conference proceedings involving esophageal cancers and reporting the overall incidence or details of treatment-related AEs (trAEs) were synthesized to determine the toxicity profile of combination treatment. We compared trAEs between cancer type, programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors, and between sequential and concurrent administration of ICIs and TRT to identify potentially high-risk patients.ResultsWe obtained toxicity data from 14 clinical trials involving 863 patients. The pooled overall incidence was 88.97% for any-grade trAEs and 18.48% for high-grade trAEs. The three most frequent non-hematologic any-grade trAEs were reactive cutaneous capillary endothelial proliferation (RCCEP, 63.80%), esophagitis (51.54%), and fatigue (33.63%). Meanwhile, RCCEP (15.69%) was the most common non-hematologic high-grade trAE, followed by nausea (4.91%) and anorexia (3.81%). The occurrence rates of any-grade and high-grade pneumonitis were 10.82% and 0.66%, respectively. In subgroup analysis, the toxicity profiles of PD-1 and PD-L1 inhibitors were mostly similar, except for any-grade pneumonitis (15.20% vs 4.88%, p=0.03) and high-grade leukopenia (6.25% vs 59.09%, p=0.00). In addition, concurrent treatment seemed to have a higher incidence of any-grade trAEs (95.20% vs 70.85%, p=0.03) compared with sequential treatment. ESCC seems to have higher incidence of any-grade hypothyroidism (22.55% vs 8.96%, p=0.049) compared to EAC.ConclusionOur study is the first systematic review to provide a toxicity profile of trAEs in esophageal cancer patients who received ICIs combined with TRT. Most AEs of this combination treatment are tolerable, although the incidence of any-grade trAEs was higher in the concurrent group. The difference in any-grade pneumonitis between PD-1 and PD-L1 inhibitor groups needs further validation in a large clinical trial.
A randomized controlled trial to verify the irrigation of salivary glands in relieving xerostomia in patients with Sjögren’s syndrome
Authors: Du Hongming , Fu Zhen , Zhong Yi , Yuan Yi , Zhao Jing , Ding Xu , Li Sheng , Gao Shiyu , Zhu Yuchi , Song Haiyang , Wu Heming 
Published: November 2022

ObjectiveTo verify the effect of triamcinolone acetonide (TA) and major salivary glands saline irrigation on relieving xerostomia in Sjögren’s syndrome (SS) patients.MethodsThe enrolled 49 SS patients were randomly assigned to the control group (no irrigation, n=16), saline group (irrigation with saline, n=17) and TA group (irrigation with TA, n=16). Fourteen cases of each group were treated differently but received the same examinations. The examinations include unstimulated whole saliva flow (UWS), chewing-stimulated whole saliva flow (SWS), citric acid-stimulated parotid flow (SPF), Clinical Oral Dryness Score (CODS), Xerostomia Inventory (XI) and EULAR SS Patient Reported Index (ESSPRI) of 1 week before irrigation (T0) and 1 week(T1), 8 weeks (T8), 16 weeks (T16) and 24 weeks (T24) after major salivary irrigation.ResultsEach group had 14 cases with completed follow-ups. Both TA and saline irrigation of major salivary glands resulted in higher SWS and SPF of T8, T16 and than those at T0. ESSPRI (oral dryness domain) of T8, T16 and T24 were significantly lower than that at T0, respectively (P &lt; 0.05). SWS and SPF of T8, T16 and T24 in the saline group were significantly higher than in the control group (P&lt; 0.05). XI and ESSPRI (oral dress domain) of T8, T16 and T24 in the saline group were significantly lower than those in the control group, respectively (P&lt; 0.05). SWS and SPF of T16 and T24 in the TA group were significantly higher than in the control group (P&lt; 0.05). All cases with completed follow-up in TA and saline groups were divided into responders and non-responders. Compared with responders, the UWS, SWS, SPF and CODS of T0 in non-responders were significantly increased (P&lt;0.05). Compared with responders, the XI and ESSPRI of T0 in non-responders were significantly decreased (P&lt;0.05).ConclusionThe irrigation of major salivary glands by TA and saline relieve xerostomia in SS patients. Patients with non-severe xerostomia (responders) have better relief after irrigation than patients with severe xerostomia (non-responders).Clinical Trial Registrationwww.chictr.org.cn, identifier (ChiCTR210052314).
Feeding juvenile largemouth bass (Micropterus salmoides) with carboxymethyl cellulose with different viscous: Impacts on nutrient digestibility, growth, and hepatic and gut morphology
Authors: Liu Yu , Fan Jiongting , Zhou Hang , Zhang Yumeng , Huang Huajing , Cao Yixiong , Zhang Wei , Deng Junming , Tan Beiping 
Published: November 2022

A 56-day trial investigated the impact of the dietary inclusion of cellulose with different viscosities on the growth, nutrient digestibility, serum biochemical indices, and the hepatic and gut morphology of largemouth bass juveniles. Four practical diets (42.50% protein and 13.70% lipid) were designed containing 8% microcrystalline cellulose (MC) and carboxymethyl cellulose (CMC) of 2,500, 5,000, and 6,500 mPa s dynamic viscosity [named MC, low-viscosity CMC (Lvs-CMC), medium-viscosity CMC (Mvs-CMC), and high-viscosity CMC (Hvs-CMC) groups, respectively]. Fish of a uniform size (6.0 g) were randomly assigned into 16 cages, with 40 fish per cage. The results showed that the protein and lipid deposition rates, specific growth rate, protein efficiency ratio, and the weight gain rate decreased significantly in the CMC groups compared to the MC group, whereas the feed intake and feed coefficient rate exhibited the opposite trend. Moreover, the intestinal Na+/K+-ATPase, alkaline phosphatase, and lipase activities significantly decreased in the Mvs-CMC and Hvs-CMC groups compared to the MC group, as well as the serum triglyceride, total cholesterol, and high-/low-density lipoprotein contents. The nutrient apparent digestibility significantly decreased in the CMC groups compared to the MC group. The viscerosomatic and intestinal length indices in the CMC groups and the villus height in the Hvs-CMC group were significantly lower than those in the MC group, whereas the number of gut goblet cells and muscular thickness in the Mvs-CMC and Hvs-CMC groups exhibited opposing results. The results also showed that dietary CMC damaged the hepatic and gut morphology and decreased the digestive enzyme activity, nutrient apparent digestibility, and growth of largemouth bass. In summary, viscosity is the main anti-nutritional effect of dietary CMC and soluble non-starch polysaccharides.
Efficacy of ozone adjuvant therapy in COVID-19 patients: A meta-analysis study
Authors: Jafari-Oori Mehdi , Vahedian-azimi Amir , Ghorbanzadeh Kobra , Sepahvand Elham , Dehi Manijeh , Ebadi Abbas , Izadi Mortaza 
Published: November 2022

IntroductionUsing ozone therapy to manage COVID-19 patients has been accompanied by conflicting results in prior studies. Therefore, we aimed to widely assess the effects of ozone as adjuvant therapy in COVID-19 patients.MethodsPubMed, Scopus, Web of Science, Cochrane, ProQuest, Springer, and Sage journals were searched systematically until April 2022. Mortality rate, ICU admission, hospital-length stay, negative PCR, pulmonary, renal, and hepatic functions, as well as inflammatory and blood systems were pooled to compare the efficacy of ozone as adjacent therapy (OZ) and standard treatment (ST). Analyses were run with the random/fixed models, sub-group analysis, funnel plot, and sensitivity analysis using comprehensive meta-analysis (CMA) software version 2.0.ResultsThe results of four randomized clinical trials (RCTs) and four case-control studies with a total of 371 COVID-19 positive patients were analyzed. The OZ group patients had a shorter length of hospital stay (P&gt; 0.05), lower ICU admissions (P&gt; 0.05), and lower mortality rates (P&lt; 0.05) than the ST group cases. After treatment, 41% more COVID-19 patients had negative PCR tests than the ST group (P&lt; 0.05). Serum creatinine and urea levels were not modified in either group (P&gt; 0.05). Moreover, except for albumin serum levels, which decreased significantly in the OZ group, serum bilirubin, ALT, and AST were not modified in either group (P&gt; 0.05). Both arms did not show a decrease in C-reactive protein blood levels (P&gt; 0.05), but the OZ group showed a significant modification in LDH serum levels (P&lt; 0.05). Unlike the d-dimer and WBC serum levels (P&gt; 0.05), platelet levels were increased in the OZ group (P&lt; 0.05). No negative side effects were demonstrated in either group.ConclusionOzone therapy was effective significantly on PCR test and LDH serum levels, as well as mortality based on overall estimation. Concerning the length of hospital stay and ICU admissions, although the results were insignificant, their effect sizes were notable clinically. More RCT studies are needed to show the efficacy of ozone therapy on other studied variables.
Multimodality imaging evaluation of nasal sinus alveolar rhabdomyosarcoma: Two case reports
Authors: Huang Wenpeng , Zhang Yongbai , Gao Ge , Li Liming , Yang Qi , Qiu Yongkang , Kang Lei 
Published: November 2022

BackgroundRhabdomyosarcoma (RMS) is a common pleomorphic malignant soft tissue sarcoma in children and adolescents that originates from rhabdomyoblasts or mesenchymal precursor cells. Alveolar rhabdomyosarcoma (ARMS) mostly occurs in adolescents aged 10–15 years and is characterized by more aggressive behaviors and worse prognosis than other sarcomas, prone to lymphatic and hematogenous metastasis in the early stage as well as metastasizing to breast, testis, pancreas, and other parts. ARMS often occurs in the limbs and genitourinary system, however, head and neck ARMS are relatively rare when involving the nasal cavity or sinuses. The role of MRI and 18F-FDG positron emission tomography combined with computed tomography (PET/CT) remains to be established in ARMS.Case reportCase 1: An 18-year-old male was found with a left submandibular mass of approximately 1 cm in diameter 2 months ago, which gradually increased in size. CT showed multiple soft tissue masses in maxillofacial and neck regions and the lesions invaded the frontal lobe and the inner wall of the left orbital lobe. MRI showed the masses with hypointensity on T1WI, hyperintensity on T2WI, and diffusion-weighted imaging (DWI) with significant enhancement. 18F-FDG PET/CT showed multiple hypermetabolic lesions located in the maxillofacial, neck region, 3rd lumbar vertebra, and the right sacrum. A nasal endoscopic tumor biopsy and molecular testing finally helped to diagnose the ARMS. Case 2: A 14-year-old male presented with left maxillary pain with nasal congestion and left ocular swelling 15 days ago. CT demonstrated a soft tissue mass in the nasal cavity and sinuses with local protrusion into the left orbit. MRI showed the masses with a slightly low signal on T1WI, a high signal on T2WI, and DWI with significant heterogenous enhancement. 18F-FDG PET/CT showed hypermetabolic lesions in the left maxillofacial and neck regions. ARMS was finally diagnosed by a nasal endoscopic tumor biopsy and molecular testing. The patient had a recurrence of the lesion after chemotherapy and surgical resection and is currently undergoing radiation therapy.ConclusionNasal sinus ARMS is highly malignant with a poor prognosis. Accurate diagnosis relies not only on histopathology and immunohistochemistry examination but also on genetic detection of characteristic chromosomal translocations and fusion genes. Imaging methods, such as MRI and PET/CT can accurately assess the extent of the lesions and metastases, assist in the diagnosis of the disease and the selection of treatment regimens, provide precise localization for surgery, and help with treatment monitoring and follow-up.
Efficacy of non-pharmacological interventions for depression in individuals with Parkinson's disease: A systematic review and network meta-analysis
Authors: Wang Yuxin , Sun Xue , Li Fei , Li Qi , Jin Yi 
Published: November 2022

BackgroundDepression in Parkinson's disease (PD) is a major health concern worldwide. Recently, an increasing number of non-pharmacological interventions have been used in PD to alleviate depressive symptoms. However, it is uncertain which intervention is the best, and related evidence is limited. This network meta-analysis was performed to compare and rank non-pharmacological interventions for PD and analyze their effects on depression to provide evidence for clinicians to choose appropriate non-pharmacological management options.MethodsThe PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PsycINFO, China National Knowledge Infrastructure (CNKI), and Wanfang databases were searched from inception to April 7, 2022. Two authors screened all studies, extracted the data, and evaluated the methodological quality. STATA software version 16.0 was used to conduct the network meta-analysis.ResultsOur network meta-analysis included 62 studies involving 3,050 participants and 35 non-pharmacological interventions. Although most non-pharmacological interventions showed non-significant effects, the surface under the cumulative ranking curve (SUCRA) values indicated that the best non-pharmacological intervention for depression was dance (82.3%), followed by LSVT-BIG therapy (77.4%), and CBT (73.6%).ConclusionDance can be considered as an effective therapy for improving depression in patients with PD. In the future, more strictly designed trials are needed to verify the conclusions of this network meta-analysis.