bluuebunny/crossref_metadata_2025 huggingface dataset:
SGLT2 inhibitors improve kidney function and morphology by regulating renal metabolic reprogramming in mice with diabetic kidney disease
Authors: Lu Yong-Ping , Zhang Ze-Yu , Wu Hong-Wei , Fang Li-Jing , Hu Bo , Tang Chun , Zhang Yi-Qing , Yin Lianghong , Tang Dong-E. , Zheng Zhi-Hua , Zhu Ting , Dai Yong
Published: September 2022

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD) worldwide. SGLT2 inhibitors are clinically effective in halting DKD progression. However, the underlying mechanisms remain unclear. The serum and kidneys of mice with DKD were analyzed using liquid chromatography with tandem mass spectrometry (LC–MS/MS)-based metabolomic and proteomic analyses. Three groups were established: placebo-treated littermate db/m mice, placebo-treated db/db mice and EMPA-treated db/db mice. Empagliflozin (EMPA) and placebo (10 mg/kg/d) were administered for 12 weeks. EMPA treatment decreased Cys-C and urinary albumin excretion compared with placebo by 78.60% and 57.12%, respectively (p < 0.001 in all cases). Renal glomerular area, interstitial fibrosis and glomerulosclerosis were decreased by 16.47%, 68.50% and 62.82%, respectively (p < 0.05 in all cases). Multi-omic analysis revealed that EMPA treatment altered the protein and metabolic profiles in the db/db group, including 32 renal proteins, 51 serum proteins, 94 renal metabolites and 37 serum metabolites. Five EMPA-related metabolic pathways were identified by integrating proteomic and metabolomic analyses, which are involved in renal purine metabolism; pyrimidine metabolism; tryptophan metabolism; nicotinate and nicotinamide metabolism, and glycine, serine and threonine metabolism in serum. In conclusion, this study demonstrated metabolic reprogramming in mice with DKD. EMPA treatment improved kidney function and morphology by regulating metabolic reprogramming, including regulation of renal reductive stress, alleviation of mitochondrial dysfunction and reduction in renal oxidative stress reaction.
Monocyte subsets display age-dependent alterations at fasting and undergo non-age-dependent changes following consumption of a meal
Authors: Snodgrass Ryan G. , Jiang Xiaowen , Stephensen Charles B.
Published: September 2022

Background

Monocytes are a heterogenous population of immune cells whose subsets and functions become substantially dysregulated with advanced age. Although much of our current understanding of the age-related changes in monocytes is derived from fasting blood samples, most people are predominately in the postprandial state during waking hours. As hormonal, metabolic, and immunological changes in response to the consumption of a meal are manifested in postprandial blood, it’s unclear how age-dependent changes in peripheral monocytes at fasting are impacted by a dietary challenge.

Objective

We investigated the impact of age and meal consumption on circulating monocyte frequencies and subsets defined as classical (CD14 + CD16-), intermediate (CD14 + CD16 +), or non-classical (CD14dim CD16 +) in a cohort of 349 healthy adult volunteers grouped into categories based on their age: young adults (18–33 y, n = 123), middle adults (34–49 y, n = 115), and older adults (50–66 y, n = 111).

Results

Following 12-h fast total monocyte counts inversely correlated with subject age. Older adults had significantly fewer circulating monocytes along with elevated levels of TGs, cholesterol, glucose, IL-6, IL-8, TNF, neopterin, and CCL2 compared with young adults. Circulating monocyte pools in older adults consisted of smaller proportions of classical but larger proportions of intermediate and non-classical monocytes. Proportions of classical monocytes were inversely correlated with plasma TNF, IL-8, and neopterin while intermediate monocytes were positively correlated with plasma IL-6, TNF, and neopterin. Three hours after consuming a fat-containing meal postprandial monocyte counts increased in all age groups. Despite age-dependent differences in monocyte subsets at fasting, consumption of a meal induced similar changes in the proportions of classical and non-classical monocytes across age groups. Within the circulating postprandial monocyte pool, percentages of classical monocytes decreased while non-classical monocytes increased. However no change in precursory intermediate monocytes were detected. Our study confirms that ageing is associated with changes in monocyte frequencies and subsets and shows that consuming a fat-containing meal induces temporal changes in monocyte frequency and subsets independently of subject age.

Clinical trial

Registered on ClincialTrials.gov (Identifier: NCT02367287)
Hybrid robot-assisted gait training for motor function in subacute stroke: a single-blind randomized controlled trial
Authors: Lin Yen-Nung , Huang Shih-Wei , Kuan Yi-Chun , Chen Hung-Chou , Jian Wen-Shan , Lin Li-Fong
Published: September 2022

Background

Robot-assisted gait training (RAGT) is a practical treatment that can complement conventional rehabilitation by providing high-intensity repetitive training for patients with stroke. RAGT systems are usually either of the end-effector or exoskeleton types. We developed a novel hybrid RAGT system that leverages the advantages of both types.

Objective

This single-blind randomized controlled trial evaluated the beneficial effects of the novel RAGT system both immediately after the intervention and at the 3-month follow-up in nonambulatory patients with subacute stroke.

Methods

We recruited 40 patients with subacute stroke who were equally randomized to receive conventional rehabilitation either alone or with the addition of 15 RAGT sessions. We assessed lower-extremity motor function, balance, and gait performance by using the following tools: active range of motion (AROM), manual muscle test (MMT), the Fugl–Meyer Assessment (FMA) lower-extremity subscale (FMA-LE) and total (FMA-total), Postural Assessment Scale for Stroke (PASS), Berg Balance Scale (BBS), Tinetti Performance-Oriented Mobility Assessment (POMA) balance and gait subscores, and the 3-m and 6-m walking speed and Timed Up and Go (TUG) tests. These measurements were performed before and after the intervention and at the 3-month follow-up.

Results

Both groups demonstrated significant within-group changes in the AROM, MMT, FMA-LE, FMA-total, PASS, BBS, POMA, TUG, and 3-m and 6-m walking speed tests before and after intervention and at the 3-month follow-up (p < 0.05). The RAGT group significantly outperformed the control group only in the FMA-LE (p = 0.014) and total (p = 0.002) assessments.

Conclusion

Although the novel hybrid RAGT is effective, strong evidence supporting its clinical effectiveness relative to controls in those with substantial leg dysfunction after stroke remains elusive.

Trial registration The study was registered with an International Standard Randomized Controlled Trial Number, ISRCTN, ISRCTN15088682. Registered retrospectively on September 16, 2016, at https://www.isrctn.com/ISRCTN15088682
Preoperative hypofractionated radiotherapy for soft tissue sarcomas: a systematic review
Authors: Roohani Siyer , Ehret Felix , Kobus Marta , Flörcken Anne , Märdian Sven , Striefler Jana Käthe , Rau Daniel , Öllinger Robert , Jarosch Armin , Budach Volker , Kaul David
Published: September 2022

Background

Soft tissue sarcomas (STS) represent a diverse group of rare malignant tumors. Currently, five to six weeks of preoperative radiotherapy (RT) combined with surgery constitute the mainstay of therapy for localized high-grade sarcomas (G2–G3). Growing evidence suggests that shortening preoperative RT courses by hypofractionation neither increases toxicity rates nor impairs oncological outcomes. Instead, shortening RT courses may improve therapy adherence, raise cost-effectiveness, and provide more treatment opportunities for a wider range of patients. Presumed higher rates of adverse effects and worse outcomes are concerns about hypofractionated RT (HFRT) for STS. This systematic review summarizes the current evidence on preoperative HFRT for the treatment of STS and discusses toxicity and oncological outcomes compared to normofractionated RT.

Methods

We conducted a systematic review of clinical trials describing outcomes for preoperative HFRT in the management of STS using PubMed, the Cochrane library, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, Embase, and Ovid Medline. We followed the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Trials on retroperitoneal sarcomas, postoperative RT, and hyperthermia were excluded. Articles published until November 30th, 2021, were included.

Results

Initial search yielded 94 articles. After removal of duplicate and ineligible articles, 13 articles qualified for analysis. Eight phase II trials and five retrospective analyses were reviewed. Most trials applied 5 × 5 Gy preoperatively in patients with high-grade STS. HFRT courses did not show increased rates of adverse events compared to historical trials of normofractionated RT. Toxicity rates were mostly comparable or lower than in trials of normofractionated RT. Moreover, HFRT achieved comparable local control rates with shorter duration of therapy. Currently, more than 15 prospective studies on HFRT + / − chemotherapy are ongoing.

Conclusions

Retrospective data and phase II trials suggest preoperative HFRT to be a reasonable treatment modality for STS. Oncological outcomes and toxicity profiles were favorable. To date, our knowledge is mostly derived from phase II data. No randomized phase III trial comparing normofractionated and HFRT in STS has been published yet. Multiple ongoing phase II trials applying HFRT to investigate acute and late toxicity will hopefully bring forth valuable findings.
Mesenchymal stem cells augmentation for surgical procedures in patients with symptomatic chondral defects of the knee: a systematic review
Authors: Filippo Migliorini , Laura Mangiavini , Riccardo Giorgino , Valeria Vismara , Eschweiler Jörg , Maffulli Nicola
Published: September 2022

Background

The efficacy and safety profile of mesenchymal stem cells (MSCs) augmentation in chondral procedures are controversial. This systematic review updated the current evidence on MSCs augmentation for chondral procedures in patients with symptomatic chondral defects of the knee.

Methods

This study followed the PRISMA guidelines. The literature search was updated in August 2022. Two independent authors accessed PubMed, Google scholar, Embase, and Scopus. No additional filters or time constrains were used for the search. A cross reference of the bibliographies was also performed. All the clinical studies investigating surgical procedures for chondral defects of the knee augmented with MSCs were accessed. Defects of both tibiofemoral and patellofemoral joints were included. The following patient reported outcomes measures (PROMs) were retrieved at baseline and last follow-up: Visual Analogic Scale (VAS), Tegner Activity Scale, Lysholm Knee Scoring System, International Knee Documentation Committee (IKDC). Return to daily activities and data on hypertrophy, failure, revision surgery were also collected. Failures were defined as the recurrence of symptoms attributable to the index procedure. Revisions were defined as any reoperation at the site of the index procedure.

Results

A total of 15 clinical studies (411 procedures) were included. Patients returned to their prior sport activity at 2.8 ± 0.4 months. All the PROMs improved at last follow-up: Tegner (P = 0.0002), Lysholm (P < 0.0001), the IKDC (P < 0.0001), VAS (P < 0.0001). At a mean of 30.1 ± 13.9 months, 3.1% (2 of 65 patients) reported graft hypertrophy, 3.2% (2 of 63) were considered failures. No surgical revision procedures were reported. Given the lack of available quantitative data for inclusion, a formal comparison of surgical procedures was not conducted.

Conclusion

MSCs augmentation in selected chondral procedures could be effective, with a low rate of complications. Further investigations are required to overcome the current limitations to allow the clinical translation of MSCs in regenerative medicine.
Pain in Rett syndrome: a pilot study and a single case study on the assessment of pain and the construction of a suitable measuring scale
Authors: Fabio Rosa Angela , Chiarini Liliana , Canegallo Virginia
Published: September 2022

Background

Rett Syndrome (RTT) is a severe, neurodevelopmental disorder mainly caused by mutations in the MECP2 gene, affecting around 1 in 10,000 female births. Severe physical, language, and social impairments impose a wide range of limitations in the quality of life of the patients with RTT. Comorbidities of patients with RTT are varied and cause a lot of pain, but communicating this suffering is difficult for these patients due to their problems, such as apraxia that does not allow them to express pain in a timely manner, and their difficulties with expressive language that also do not permit them to communicate. Two studies, a pilot study and a single case study, investigate the manifestation of pain of patients with RTT and propose a suitable scale to measure it.

Aims of this study

The first aim was to describe pain situations of RTT by collecting information by parents; the second aim was to test and compare existing questionnaires for non-communicating disorders on pain such as Pain assessment in advanced demenzia (PAINAD), the Critical care pain observation tool (CPOT) and the Non-communicating Children’s Pain Checklist-Revised (NCCPC-R) to assess which of them is best related to the pain behavior of patients with RTT. The third aim was to identify the specific verbal and non-verbal behaviors that characterize pain in girls with Rett syndrome, discriminating them from non-pain behaviors.

Method

Nineteen participants, eighteen girls with RTT and one girl with RTT with 27 manifestations of pain were video-recorded both in pain and base-line conditions. Two independent observers codified the 90 video-recording (36 and 54) to describe their behavioral characteristics.

Results

The two studies showed that the most significant pain behaviors expressed by girls with respect to the baseline condition, at the facial level were a wrinkled forehead, wide eyes, grinding, banging teeth, complaining, making sounds, crying and screaming, and the most common manifestations of the body were tremors, forward and backward movement of the torso, tension in the upper limbs, increased movement of the lower limbs and a sprawling movement affecting the whole body.

Conclusion

The results of the two studies helped to create an easy-to-apply scale that healthcare professionals can use to assess pain in patients with Rett’s syndrome. This scale used PAINAD as its basic structure, with some changes in the items related to the behavior of patients with RTT.
Naturally derived indole alkaloids targeting regulated cell death (RCD) for cancer therapy: from molecular mechanisms to potential therapeutic targets
Authors: Qin Rui , You Feng-Ming , Zhao Qian , Xie Xin , Peng Cheng , Zhan Gu , Han Bo
Published: September 2022

Regulated cell death (RCD) is a critical and active process that is controlled by specific signal transduction pathways and can be regulated by genetic signals or drug interventions. Meanwhile, RCD is closely related to the occurrence and therapy of multiple human cancers. Generally, RCD subroutines are the key signals of tumorigenesis, which are contributed to our better understanding of cancer pathogenesis and therapeutics. Indole alkaloids derived from natural sources are well defined for their outstanding biological and pharmacological properties, like vincristine, vinblastine, staurosporine, indirubin, and 3,3′-diindolylmethane, which are currently used in the clinic or under clinical assessment. Moreover, such compounds play a significant role in discovering novel anticancer agents. Thus, here we systemically summarized recent advances in indole alkaloids as anticancer agents by targeting different RCD subroutines, including the classical apoptosis and autophagic cell death signaling pathways as well as the crucial signaling pathways of other RCD subroutines, such as ferroptosis, mitotic catastrophe, necroptosis, and anoikis, in cancer. Moreover, we further discussed the cross talk between different RCD subroutines mediated by indole alkaloids and the combined strategies of multiple agents (e.g., 3,10-dibromofascaplysin combined with olaparib) to exhibit therapeutic potential against various cancers by regulating RCD subroutines. In short, the information provided in this review on the regulation of cell death by indole alkaloids against different targets is expected to be beneficial for the design of novel molecules with greater targeting and biological properties, thereby facilitating the development of new strategies for cancer therapy.

Graphic abstract
Application of metabolomics in intrahepatic cholestasis of pregnancy: a systematic review
Authors: Yang Zhuoqiao , Yao Mengxin , Zhang Chunhua , Hu Xuan , Zhong Yi , Xu Xiangxiang , Yin Jieyun
Published: September 2022

Background

Intrahepatic cholestasis of pregnancy (ICP) is a severe idiopathic disorder of bile metabolism; however, the etiology and pathogenesis of ICP remain unclear.

Aims

This study comprehensively reviewed metabolomics studies related to ICP, to help in identifying the pathophysiological changes of ICP and evaluating the potential application of metabolomics in its diagnosis.

Methods

Relevant articles were searched through 2 online databases (PubMed and Web of Science) from January 2000 to March 2022. The metabolites involved were systematically examined and compared. Pathway analysis was conducted through the online software MetaboAnalyst 5.0.

Results

A total of 14 papers reporting 212 metabolites were included in this study. There were several highly reported metabolites: bile acids, such as glycocholic acid, taurochenodeoxycholic acid, taurocholic acid, tauroursodeoxycholic acid, and glycochenodeoxycholic acid. Dysregulation of metabolic pathways involved bile acid metabolism and lipid metabolism. Metabolites related to lipid metabolism include phosphatidylcholine, phosphorylcholine, phosphatidylserine, sphingomyelin, and ceramide.

Conclusions

This study provides a systematic review of metabolomics of ICP and deepens our understanding of the etiology of ICP.
Barking up the wrong biomarker? Correspondence to Shobeiri et al. (2022) “Serum and plasma levels of brain-derived neurotrophic factor in individuals with eating disorders (EDs): a systematic review and meta-analysis”
Authors: Steinhäuser Jonas L. , Wronski Marie-Louis , Keeler Johanna L. , Ehrlich Stefan , King Joseph A.
Published: September 2022

Despite intensified research efforts into the underlying (neuro-)biology of eating disorders (EDs), only few reliable biomarkers of diagnostic or prognostic value have been identified to date. One promising line of research has focused on the role of peripheral blood-based biomarkers as potential contributors to the complex pathophysiology of EDs. One such candidate marker is brain-derived neurotrophic factor (BDNF), a neurotrophin broadly implicated in neuronal plasticity and food-intake regulation. A growing number of studies have targeted BDNF in EDs; culminating in several recent well-powered and controlled case–control studies, comprehensive meta-analyses, and review articles. In the current correspondence, we aim to put the recent meta-analysis of Shobeiri et al. (J Eat Disord 10(1):105, 2022) into perspective and argue that the finding suggestive of lower BDNF concentrations across individuals with EDs in comparison to healthy controls needs to be interpreted with caution. While this finding is compatible with those from earlier meta-analyses, it may be biased due to several reasons; most notably by the applied study selection procedures, insufficient consideration of influential determinants of BDNF concentrations, and generalization of results across the ED spectrum without sufficient statistical power. Further controlled and comprehensive studies are necessary to establish BDNF as a clinically informative biomarker of EDs.
Foreign body-type giant cell reaction with extensive granulation tissue and intense inflammation after chemotherapy mimicking residual lymphoma on FDG PET
Authors: Kazi Sakib , Raptis Stavros , Abbaspour Farzad , Zeng Wanzhen
Published: September 2022

Foreign body-type giant cell reaction is typically a biological and immunological reaction to the presence of foreign bodies such as catheters, parasites or biomaterials with a collection of fused macrophages (giant cell). We reported an unusual case of [18F]FDG PET findings in diffuse large B cell lymphoma in the urinary bladder following incomplete resection and chemotherapy. As the restaging [18F]FDG PET showed intense [18F]FDG uptake in the urinary bladder at the resection site concerning for recurrence, the lesion was subsequently resected and histopathology showed extensive granulation tissue with foreign body-type giant cell reaction with no suspected foreign bodies or neoplasia.
The improvement of dispersity, thermal stability and mechanical properties of collagen fibers by silane modification: an exploration for developing new leather making technology
Authors: Xu Shuangfeng , Xiao Hanzhong , Shi Bi
Published: September 2022

The effect of hydrophobic modification on the performances of collagen fibers (CFs) was investigated by using silane coupling agents with different alkyl chains as hydrophobic modifiers. It was found silane could be easily grafted onto CF surface through covalent bonds under 5% water content. This modification led to the transformation of surface wettability of CF from hydrophilic to hydrophobic. Interestingly, the change of surface wettability resulted in substantial improvement of the modified CF properties, presenting well dispersity of collagen fibers, higher thermal stability and enhanced mechanical properties in comparison with natural CF. The degree of improvement mainly depended on the length of alkyl chain in silane. Longer alkyl chain produced strong hydrophobicity and subsequently more superior performances of the modified CF. When the length of alkyl chain increased to 18 carbon atoms, the modified CF possessed durable superhydrophobicity even exposed to aqueous solutions of different pH, UV, and organic solvents, and had excellent thermal and mechanical properties like leather fibers. In general, this work clearly revealed that the properties of CF are closely and positively related to the hydrophobicity, which is suggestive in developing new leather making technology.

Graphical Abstract
Post-COVID-19 acute invasive fungal rhinosinusitis: a systematic radiological approach in the light of clinico-surgical characteristics
Authors: Shaban Ekhlas , Saleh Rasha Aly , Ammar Mostafa Ibrahim , Ebeid Kamal
Published: September 2022

Background

The objective is to describe the radiological imaging findings of post-COVID-19 acute invasive fungal rhinosinusitis (AIFRS), being familiar with the wide variety of imaging spectrum, thus raising the suspicion for early diagnosis. Methods: In this retrospective study, we reviewed the imaging findings in 54 patients with proven post-COVID-19 AIFRS who underwent endoscopic/surgical debridement from April 2020 to September 2021. Most of these patients presented with facial or orbital swelling or facial pain. Medical records with a special emphasis on radiological imaging (50 NCCT of the paranasal sinuses and 17 MRIs of the orbit) were reviewed regarding the degree of mucosal disease of sinuses, nasal cavity, and nasopharynx, extra sinus soft tissue infiltration, especially orbital and cerebral extension (parenchymal, cavernous sinus, vascular or neuro-invasion).

Results

We reported findings in 54 patients with post-COVID-19 AIFRS, of whom 30 were men and 24 were women with a mean age of 48.06. Unexpectedly, infiltration of pterygopalatine fossa was found to precede mucosal opacification of sinuses nasal cavity and affection of nasopharynx. Out of 54 patients, 49 showed inflammatory changes involving pterygopalatine fossa, 29.6% of patients showed infiltration of orbital tissues, 22 patients suffered from a fungal invasion of the cavernous sinus and 3 patients had carotid artery involvement.

Conclusions

Imaging findings of AIFRS significantly vary from subtle mucosal thickening of paranasal sinuses, up to orbital and intracranial extension with vascular thrombosis and neuroinvasion. The hallmark inflammatory tissue infiltration into the pterygopalatine fossa and facial soft tissue may precede mucosal disease.
Assessment of carotid atherosclerosis in Egyptian chronic hepatitis C patients after treatment by direct-acting antiviral drugs
Authors: Mohamed Marwa Ahmed , Bayoumy Essam M. , Swailam Mostafa Mohamed , Allam Ahmed Samir
Published: September 2022

Background

Recent studies suggested association between hepatitis C virus (HCV) infection and cardiovascular disorders, including carotid atherosclerosis with evidence of an effect of HCV clearance on carotid atherosclerosis.

Objectives

We aimed to evaluate the impact of direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection on carotid atherosclerosis.

Subjects and methods

This is a prospective cohort study that was carried out in Internal Medicine and Hepatology Department, and outpatient clinics of the Ain Shams University hospitals included 80 Egyptian patients with chronic HCV infection who started treatment in the form of IFN-free DAA-based regimen and completed the course of treatment and 6-month follow-up period. All patients were subjected to detailed history taking, full physical examination, full laboratory investigations, radiological assessment by abdominal ultrasonography, and high-resolution B-mode ultrasonography of both the common carotid arteries.

Results

The mean age of cases was 58.13 ± 7.56 years, 49 (61.25%) males and 31 (38.75%) females. IMT was significantly decreased after treatment 1.24 versus 1.57 mm p < 0.001. The number of patients with IMT ≥ 1 mm was significantly decreased after 6 months 45 (56.3%) versus 57 (71.3%). There was significant positive correlation between baseline carotid IMT and age, BMI, bilirubin, INR, CTP score, carotid plaques, and total cholesterol. Meanwhile, there was significant negative correlation between baseline carotid IMT and hemoglobin, platelets, albumin, and HDL. In patients who achieved SVR, total cholesterol, triglycerides, LDL, and HDL were significantly increased after treatment. IMT was significantly lower in SVR group compared to non-SVR group (p = 0.016).

Conclusion

Hepatitis C virus eradication by DAAs improves carotid atherosclerosis by decreasing carotid intima-media thickening.
Natural Language Processing of Computed Tomography Reports to Label Metastatic Phenotypes With Prognostic Significance in Patients With Colorectal Cancer
Authors: Causa Andrieu Pamela , Golia Pernicka Jennifer S. , Yaeger Rona , Lupton Kaelan , Batch Karen , Zulkernine Farhana , Simpson Amber L. , Taya Michio , Gazit Lior , Nguyen Huy , Nicholas Kevin , Gangai Natalie , Sevilimedu Varadan , Dickinson Shannan , Paroder Viktoriya , Bates David D.B. , Do Richard
Published: September 2022

PURPOSE

Natural language processing (NLP) applied to radiology reports can help identify clinically relevant M1 subcategories of patients with colorectal cancer (CRC). The primary purpose was to compare the overall survival (OS) of CRC according to American Joint Committee on Cancer TNM staging and explore an alternative classification. The secondary objective was to estimate the frequency of metastasis for each organ.

METHODS

Retrospective study of CRC who underwent computed tomography (CT) chest, abdomen, and pelvis between July 1, 2009, and March 26, 2019, at a tertiary cancer center, previously labeled for the presence or absence of metastasis by an NLP prediction model. Patients were classified in M0, M1a, M1b, and M1c (American Joint Committee on Cancer), or an alternative classification on the basis of the metastasis organ number: M1, single; M2, two; M3, three or more organs. Cox regression models were used to estimate hazard ratios; Kaplan-Meier curves were used to visualize survival curves using the two M1 subclassifications.

RESULTS

Nine thousand nine hundred twenty-eight patients with a total of 48,408 CT chest, abdomen, and pelvis reports were included. On the basis of NLP prediction, the median OS of M1a, M1b, and M1c was 4.47, 1.72, and 1.52 years, respectively. The median OS of M1, M2, and M3 was 4.24, 2.05, and 1.04 years, respectively. Metastases occurred most often in liver (35.8%), abdominopelvic lymph nodes (32.9%), lungs (29.3%), peritoneum (22.0%), thoracic nodes (19.9%), bones (9.2%), and pelvic organs (7.5%). Spleen and adrenal metastases occurred in < 5%.

CONCLUSION

NLP applied to a large radiology report database can identify clinically relevant metastatic phenotypes and be used to investigate new M1 substaging for CRC. Patients with three or more metastatic disease organs have the worst prognosis, with an OS of 1 year.
Natural Language Processing Approaches for Automated Multilevel and Multiclass Classification of Breast Lesions on Free-Text Cytopathology Reports
Authors: Nandish Sonali , R.J. Prathibha , N.M. Nandini
Published: September 2022

PURPOSE

The extensive growth and use of electronic health records (EHRs) and extending medical literature have led to huge opportunities to automate the extraction of relevant clinical information that helps in concise and effective clinical decision support. However, processing such information has traditionally been dependent on labor-intensive processes with human errors such as fatigue, oversight, and interobserver variability. Hence, this study aims at the processing of EHRs and performing multilevel and multiclass classification by fetching dominant characteristic features that are sufficient to detect and differentiate various types of breast lesions.

PATIENTS AND METHODS

In this study, unstructured EHRs on breast lesions obtained through fine-needle aspiration cytology technique are considered. The raw text was normalized into structured tabular form and converted to scores by performing sentiment analysis that helps to decide the total polarity or class label of the EHR. Supervised machine learning approaches, namely random forest and feed-forward neural network trained using Levenberg-Marquardt training function, are used for classification of the collected EHR data set containing 2,879 records that are split in the ratio of 80:20 as training and testing data sets, respectively.

RESULTS

Random forest and feed-forward neural network classifiers gave the best performance with an accuracy of 99.36%, an overall receiver operating characteristic-area under the curve of 99.2%, a correlation with ground truth of 98.3%, and a histopathologic correlation of 98.6%.

CONCLUSION

Natural language processing has huge potential to automate the extraction of clinical features from breast lesions. The proposed multilevel and multiclass classification approach is used to classify 13 different types of breast lesions with 20 different labels into five classes to decide the type of treatment that should be given to patients by a physician or oncologist.
Safety and Efficacy of Pediatric Growth Hormone Therapy: Results From the Full KIGS Cohort
Authors: Maghnie Mohamad , Ranke Michael B , Geffner Mitchell E , Vlachopapadopoulou Elpis , Ibáñez Lourdes , Carlsson Martin , Cutfield Wayne , Rooman Raoul , Gomez Roy , Wajnrajch Michael P , Linglart Agnès , Stawerska Renata , Clayton Peter E , Darendeliler Feyza , Hokken-Koelega Anita C S , Horikawa Reiko , Tanaka Toshiaki , Dörr Helmuth-Günther , Albertsson-Wikland Kerstin , Polak Michel , Grimberg Adda
Published: September 2022

Context

The Kabi/Pfizer International Growth Database (KIGS) is a large, international database (1987-2012) of children treated with recombinant human growth hormone (rhGH) in real-world settings.

Objective

This work aimed to evaluate the safety and efficacy of rhGH from the full KIGS cohort.

Methods

Data were collected by investigators from children with growth disorders treated with rhGH (Genotropin [somatropin]; Pfizer). Safety was evaluated in all treated patients, and efficacy in those treated for 1 year or more. A subgroup included patients treated for 5 years or more (≥ 2 years prepubertal) who had reached near-adult height (NAH). Main outcomes included adverse events (AEs), serious AEs (SAEs), and height growth.

Results

The full KIGS cohort (N = 83 803 [58% male]) was treated for idiopathic GH deficiency (IGHD; 46.9%), organic GHD (10.0%), small for gestational age (SGA; 9.5%), Turner syndrome (TS; 9.2%), idiopathic short stature (ISS; 8.2%), and others (16.2%). Median rhGH treatment duration was 2.7 years and observation 3.1 years. SAEs occurred in 3.7% of patients and death in 0.4%. The most common SAEs were recurrence of craniopharyngioma (n = 151), neoplasm (n = 99), and cancer (n = 91); and scoliosis (n = 91). Median first-year delta height-SD score (SDS) (Prader) in prepubertal patients was 0.66 (IGHD), 0.55 (ISS), 0.58 (TS), and 0.71 (SGA). Median gains in NAH-SDS were 1.79 (IGHD), 1.37 (ISS), and 1.34 (SGA) for boys, and 2.07 (IGHD), 1.62 (ISS), 1.07 (TS), and 1.57 (SGA) for girls.

Conclusion

Data from KIGS, the largest and longest running international database of rhGH-treated children, show that rhGH is safe and increases short-term height gain and adult height across GHD and non-GHD conditions.
Evaluating the Progression to Hypothyroidism in Preconception Euthyroid Thyroid Peroxidase Antibody–Positive Women
Authors: Gill Sofia , Cheed Versha , Morton Victoria A H , Gill Dayna , Boelaert Kristien , Chan Shiao , Coomarasamy Arri , Dhillon-Smith Rima K
Published: September 2022

Context

Thyroid peroxidase antibody (TPOAb) positivity is prevalent in women of reproductive age and predisposes to thyroid dysfunction, particularly hypothyroidism, which has adverse effects on pregnancy.

Objective

This study aimed to report the rate of development of abnormal thyroid function among initially euthyroid TPOAb-positive women recruited into the TABLET trial, to identify factors associated with the development of hypothyroidism, and to compare outcomes between euthyroid and treated hypothyroid individuals.

Methods

This observational cohort study, conducted at 49 UK hospitals between 2011 and 2016, included euthyroid TPOAb-positive women 16 to 40 years of age with a history of miscarriage or subfertility, planning pregnancy, randomized to levothyroxine 50 mcg daily or placebo. Abnormal thyroid function, conception rate, and live birth rate (LBR) ≥34 weeks were analyzed.

Results

Among the women, 70/940 (7.4%) developed subclinical (SCH) or overt (OH) hypothyroidism: 27/470 taking levothyroxine and 43/470 placebo (relative risk [RR] 0.63; 95% CI, 0.39-1.00; P = 0.05); 83% of cases emerged prepregnancy. Baseline median serum TSH concentrations and TPOAb titers were significantly higher in those who developed hypothyroidism vs those who did not (P < 0.001). Treated SCH/OH demonstrated a higher failure-to-conceive rate compared with euthyroid women (adjusted RR 2.02 [1.56-2.62]; P < 0.001). The LBR ≥ 34 weeks was similar in the treated SCH/OH and euthyroid groups (adjusted RR 1.09 [0.77-1.55]; P = 0.6).

Conclusion

Approximately 7% of euthyroid TPOAb-positive women will develop hypothyroidism within 1 year preconception or in pregnancy. Conception rates are lower in women with treated SCH/OH compared with euthyroid women, but LBR are comparable. Thyroid function in TPOAb-positive women should be monitored regularly, when trying to conceive, to ensure prompt diagnosis and appropriate treatment initiation.
Identification of 4 New Loci Associated With Primary Hyperparathyroidism (PHPT) and a Polygenic Risk Score for PHPT
Authors: Soto-Pedre Enrique , Newey Paul J , Srinivasan Sundararajan , Siddiqui Moneeza K , Palmer Colin N A , Leese Graham P
Published: September 2022

Context

A hypothesis-free genetic association analysis has not been reported for patients with primary hyperparathyroidism (PHPT).

Objective

We aimed to investigate genetic associations with PHPT using both genome-wide association study (GWAS) and candidate gene approaches.

Methods

A cross-sectional study was conducted among patients of European White ethnicity recruited in Tayside (Scotland, UK). Electronic medical records were used to identify PHPT cases and controls, and linked to genetic biobank data. Genetic associations were performed by logistic regression models and odds ratios (ORs). The combined effect of the genotypes was researched by genetic risk score (GRS) analysis.

Results

We identified 15 622 individuals for the GWAS that yielded 34 top single-nucleotide variations (formerly single-nucleotide polymorphisms), and LPAR3-rs147672681 reached genome-wide statistical significance (P = 1.2e-08). Using a more restricted PHPT definition, 8722 individuals with data on the GWAS-identified loci were found. Age- and sex-adjusted ORs for the effect alleles of SOX9-rs11656269, SLITRK5-rs185436526, and BCDIN3D-AS1-rs2045094 showed statistically significant increased risks (P < 1.5e-03). GRS analysis of 5482 individuals showed an OR of 2.51 (P = 1.6e-04), 3.78 (P = 4.0e-08), and 7.71 (P = 5.3e-17) for the second, third, and fourth quartiles, respectively, compared to the first, and there was a statistically significant linear trend across quartiles (P < 1.0e-04). Results were similar when stratifying by sex.

Conclusion

Using genetic loci discovered in a GWAS of PHPT carried out in a Scottish population, this study suggests new evidence for the involvement of genetic variants at SOX9, SLITRK5, LPAR3, and BCDIN3D-AS1. It also suggests that male and female carriers of greater numbers of PHPT-risk alleles both have a statistically significant increased risk of PHPT.
RNA modifications: an overview of select web-based tools
Authors: Ramos Jillian
Published: September 2022

The field of epitranscriptomics has expanded dramatically in recent years, both in the number of identified RNA modifications and the number of researchers studying them. As knowledge of post-transcriptional modifications continues to expand, numerous new methods have been developed to detect these modifications. Additionally, modifications are being extended to therapeutic settings, such as with recent mRNA vaccines. With this increase in knowledge and use, the community is recognizing the necessity for user-friendly databases to (i) store information from both high- and low-throughput studies and (ii) provide prediction software on how RNA modifications contribute to RNA function and disease. This mini-review highlights select RNA modification databases and their key attributes with the aim of providing a resource to researchers in the field of epitranscriptomics.
Integrated approach of raw and modified fibrous clay minerals application for nitrate and ammonium removal from water systems
Authors: Λαζαράτου Χριστίνα-Βασιλική
Published: September 2022

Η συγκεκριμένη μελέτη επικεντρώνεται στην ολοκληρωμένη διαχείριση των ινωδών αργιλικών ορυκτών σαν προσροφητές νιτρικού (NO3--N) και αμμωνιακού αζώτου (NH4+-N). O παλυγορσκίτης και ο σεπιόλιθος επιλέχθηκαν σαν φιλικά υλικά/ προσροφητές, εξίσου ως προς τον άνθρωπο και το περιβάλλον, για την απομάκρυνση νιτρικού και αμμωνιακού αζώτου από ρυπασμένους υδροφόρους. Συγκεκριμένα, η δυνατότητα επαναχρησιμοποίησής τους, ο ρυθμός εκρόφησης, καθώς και η μετέπειτα διαχείριση τους διερευνήθηκαν εκτενώς. Επίσης, για να επιτευχθεί ακόμα μεγαλύτερη ικανότητα απομάκρυνσης, ο παλυγορσκίτης και ο σεπιόλιθος δέχθηκαν όξινη και θερμική τροποποίηση με υδροχλωρικό οξύ (1Μ) και ξήρανση στους 400 oC αντίστοιχα. Οι συγκεκριμένες τεχνικές επιλέχθηκαν ανάμεσα σε πολλές λόγω της απλότητας της διαδικασίας τους καθώς και τη διατήρηση της φιλικότητας προς το περιβάλλον. Προκειμένω να προσδιοριστούν οι βέλτιστες συνθήκες για την απομάκρυνση και των δύο αζωτούχων ρύπων, διεξήχθησαν πειράματα σε υδατικά διαλύματα (batch πειράματα, λαμβάνοντας υπόψιν την επίδραση της μάζας προσροφητή, την αρχική συγκέντρωση του ρύπου, pH) και σε στήλες συνεχούς ροής, εξετάζοντας διαφορετικές τιμές παροχών. Ο ακριβής μηχανισμός απομάκρυνσης του εκάστοτε ρύπου διερευνήθηκε χρησιμοποιώντας τις τεχνικές χαρακτηρισμού XRD, SEM, BET, FT-IR, TGA, δυναμικό -ζ και XRF, καθώς και μέσω μοριακής μοντελοποίησης.
Resisting austerity
Authors: Αραμπατζή Αθηνά
Published: September 2022

Οι πρόσφατες διαμαρτυρίες που λαμβάνουν χώρα σε πόλεις σε όλο τον κόσμο έχουν εκφράσει αντίθεση στη συνεχιζόμενη κρίση της νεοφιλελεύθερης παγκοσμιοποίησης και τα αποτελέσματά της σε διαφορετικά γεωγραφικά πλαίσια. Από τους Ισπανούς "Αγανακτισμένους" μέχρι την κατάληψη της Πλατείας Συντάγματος στην Αθήνα και το κίνημα Occupy στις ΗΠΑ, οι αναδυόμενες μορφές διαμφισβητούμενων πολιτικών έχουν αναζωπυρώσει κρίσιμες συζητήσεις για τις πόλεις και τα κοινωνικά κινήματα. Ωστόσο, οι υποκείμενες διαδικασίες μέσω των οποίων αυτές αναδύονται και αναπτύσσονται, καθώς και οι δυνατότητες και οι περιορισμοί τους στην άρθρωση προκλήσεων προς την τελευταία φάση της νεοφιλελεύθερης αναδιάρθρωσης και λιτότητας, παραμένουν σε εξέλιξη. Η παρούσα διατριβή ασχολείται με αυτές τις υπό ανάπτυξη αναλυτικές εστίες σχετικά με τις αναδυόμενες διαμφισβητούμενες πολιτικές σε πλαίσια που καθοδηγούνται από τη λιτότητα μέσω της περίπτωσης της Αθήνας, στην Ελλάδα. Εντάσσεται, δε, σε ένα ευρύτερο πλαίσιο συζητήσεων για τις πόλεις και τις γεωγραφίες των κοινωνικών κινημάτων και βασίζεται σε ποιοτικά δεδομένα που συγκεντρώθηκαν κατά τη διάρκεια επιτόπιας έρευνας και την κριτική εμπλοκή σε αγώνες στην Αθήνα, έτσι ώστε να εξετάσει τις διαδικασίες που επιτρέπουν στις διαμφισβητούμενες πρακτικές να υλοποιηθούν και να επεκταθούν στο χώρο.Ειδικότερα, προτείνεται ότι οι πολιτικές λιτότητας και τα αποτελέσματά τους στον πληθυσμό της πόλης έχουν προκαλέσει αντιδράσεις από τη βάση που αμφισβητούν τη λιτότητα και παράγουν εναλλακτικές πρακτικές λύσεις για την αντιμετώπιση των επιτακτικών αναγκών της κοινωνικής αναπαραγωγής. Αυτές αρθρώνονται μέσω πρακτικών αντίστασης και αλληλεγγύης, οι οποίες εδράζονται σε τοπικά πλαίσια, δηλαδή στις γειτονιές της Αθήνας, και συγκροτούνται αμοιβαία με ευρύτερες εναλλακτικές λύσεις και πολιτικές κατά της λιτότητας που εκτυλίσσονται χωρικά σε όλη την πόλη και πέραν αυτής. Ως εκ τούτου, αναπτύσσονται οι ιδέες των "κοινοτήτων αγώνα" και των "αστικών χώρων αλληλεγγύης" που καταδεικνύουν: πρώτον, τη διαδικασία της ανάδυσης και της ανάπτυξης πρακτικών αντίστασης και αλληλεγγύης σε επίπεδο γειτονιάς και τις σχεσιακές διασυνδέσεις τους εξωστρεφώς; και, δεύτερον, τη διαδικασία της επέκτασης αυτών σε όλο το χώρο της πόλης, σε εθνικό επίπεδο και διαμέσου διασυνδέσεων με ευρωπαϊκά κινήματα κατά της λιτότητας, δηλαδή τακτικών δικτύωσης και συνεργασίας μεταξύ τοπικών πρωτοβουλιών, της διαμόρφωσης μιας κοινωνικής/ αλληλέγγυας οικονομίας καθώς και ευρύτερων στρατηγικών κοινωνικής ενδυνάμωσης και αλλαγής.
About the Theoretical Foundation of Audit and Other Economic Sciences
Authors: Guttsayt E.
Published: September 2022

The article considers three levels of audit science: the concept of audit, its theoretical founda-tions, specific scientific provisions. It is analyzed in detail why the concept of audit and its theo-retical foundations are needed. It is considered what contribution to the theoretical foundations of audit is made (or can be made) by other sciences: accounting, probability theory, economic competition, pricing, efficiency, industry markets, regulation in the socio-economic sphere, sys-tems engineering, science of science, etc. It is illustrated that the use of developments and meth-ods of other sciences in audit usually gives better results than attempts to solve the problem au-tonomously. The possibilities of transferring ideas about the concept and the theoretical founda-tions of audit to other economic sciences are fragmentarily investigated.
Ischemic stroke in a pediatric patient – a case report
Authors: Głaz Aneta , Knop Kinga , Kochanowska Anna , Nowicki-Sak Karol , Woźniak Magdalena
Published: September 2022

Background

Childhood ischemic stroke (AIS) is a relatively rare disease with an estimated incidence of 1.3-13/100,000/year. It most commonly affects children under the age of 5. Major risk factors include arteriopathies, heart disease, hypercoagulable states and infections.

Case report

A 2-year-old patient was admitted to the Department of Neurology at the University Children's Hospital in Lublin after suffering a head injury 3 days earlier. Neurological examination revealed features of left hemiparesis. A CT scan revealed an uncharacteristic hypodense, poorly demarcated area, an indication for further diagnostics. MR imaging revealed diffuse ischemic lesions. Angio-MR showed a lack of signal within the branches of the right posterior cerebral artery. Based on the clinical picture and additional examinations, a diagnosis of ischemic stroke was made and pharmacological treatment was implemented. To determine the cause of the stroke, an echocardiogram was performed, which showed flaccid atrial septal tissue with a defect and a trace left-right leak. Genetic testing for congenital thrombophilia confirmed a 4G/4G polymorphism in the PAI-1 gene.

Conclusions

Ischemic stroke is a life-threatening condition that requires prompt diagnosis and appropriate treatment. The relatively rare occurrence among children and nonspecific symptoms may result in difficulties in making a definitive diagnosis. Each case of stroke in children requires a comprehensive diagnosis including neuroimaging studies and identification of specific risk factors.
(Za)pamiętany obraz „słodkiego” dzieciństwa, czyli opowieści o maszketach
Authors: Świtała-Trybek Dorota
Published: September 2022

Przedmiotem artykułu są wspomnienia rodowitych Ślązaków dotyczące dzieciństwa, a dokładnie wybranego elementu dziedzictwa kulturowego, jakim są słodycze, w gwarze śląskiej określane jako maszkety. Zaprezentowane wypowiedzi autorka zarejestrowała podczas badań terenowych prowadzonych na Górnym Śląsku, w obrębie dwóch województw: opolskiego i śląskiego w latach 2019-2021 w społecznościach zarówno wiejskich, jak i miejskich. Zgromadzone materiały pozwalają spojrzeć na dzieciństwo od czasów powojennych do lat 80. XX w. przez pryzmat konkretnych artykułów żywnościowych, ich miejsca i znaczenia w życiu dzieci. Dostarczają wielu interesujących informacji na temat samych łakoci oraz okoliczności ich przyrządzania i spożywania, a także funkcjonujących dawniej warunków życia, przemian modeli w zakresie odżywiania, obchodzenia uroczystości i świąt w rodzinach.
Wysokie mniamanie. Jedność i jedzenie w cyklu opowiadań o Panu Kuleczce Wojciecha Widłaka
Authors: Marzoch Małgorzata
Published: September 2022

Jedzenie – zarówno sama czynność, jak i rozmaitość potraw – funkcjonuje współcześnie jako supermetafora, ogarniająca wiele sfer ludzkiej aktywności. W niniejszym artykule przyjrzę się relacji między wspólnotą rodzinną i posiłkami (ich rodzajami, produktami spożywczymi, okolicznościami, w jakich jedzą bohaterowie) w cyklu opowiadań o Panu Kuleczce Wojciecha Widłaka. Ukazane w swoiście realistycznej konwencji jedzenie towarzyszy codziennym przygodom bohaterów, będąc przyjemnością, niewinną słabostką, pocieszeniem, metaforą miłości, zawsze wyrażając harmonijne doświadczenie kosmosu życia rodzinnego. W zaproponowanej interpretacji wykorzystam pojęcia eros, agape oraz koncepcję psychologii moralności Jonathana Haidta.