bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dietary treatment of congenital chylothorax with skimmed breast milk
Authors: Höck Michaela , Höller Alexander , Hammerl Marlene , Wechselberger Karina , Krösslhuber Jakob , Kiechl-Kohlendorfer Ursula , Scholl-Bürgi Sabine , Karall Daniela 
Published: August 2021

AbstractBackgroundCongenital chylothorax (CC) is a rare but potentially life-threatening condition in newborns. It is defined as an accumulation of chyle in the pleural cavity. The few publications regarding medical management and therapeutic dietary intervention motivated us to share our experience.MethodsNeonates diagnosed with congenital chylothorax and treated at Innsbruck Medical University Hospital between 2013 and 2020 (n = 6, gestational age: 36 3/7, 32 5/7, 36 4/7, 35 0/7, 35 4/7, 37 3/7 weeks) were eligible for this report.The cornerstones of treatment for chylothorax conventionally consist of chest tube drainage (CTD), respiratory support, dietary restriction of long-chain triglycerides (LCT) or total parenteral nutrition (TPN). In further course the introduction of a medium-chain triglyceride (MCT)-based formula followed by an overlapping switch to a formula with low LCT and high MCT, containing the essential long-chain fatty acids (LCFA), is attempted. In three patients we used fat-modified (skimmed) breast milk to provide a high protein and low fat diet and to avoid the discontinuation of breast milk.ResultsThe outcome of an early introduction of LCFA in the form of skimmed breast milk after resolution of chylothorax diverse. One patient had a favourable outcome, meaning no recurrence of pleural effusion, adequate weight gain and a content mother, while another patient had a relapse of pleural effusion after the administration of skimmed milk and was therefore transitioned back to Basic F® .The CC of patient 5 was difficult due to Noonan syndrome. Two weeks after the introduction of skimmed breast milk the mother wanted to stop to express breast milk, so nutrition was changed to Basic F®.ConclusionThe first-line therapy of chylothorax is a combination of respiratory stabilization and dietary modification. The use of skimmed breast milk is advisable in CC and feasible by means of a simple milk defatting procedure. It offers benefits to mothers who wish to resume breast feeding after resolution of chylothorax and has proven positive effects, above all in preterm infants as optimal nutrition with protective components superior to formula feeding. However, the nutritional analysis of the skimmed milk and the correlation to a re-accumulation of pleural fluid remains a question to be answered.
IL-23/Th17 pathway and IL-17A gene polymorphism in Egyptian children with immune thrombocytopenic purpura
Authors: Ismail Ahlam M. , Higazi Aliaa M. , Nomeir Hanan M. , Farag Naglaa M. 
Published: August 2021

Abstract
Background
Immune thrombocytopenic purpura (ITP) is an acquired complex autoimmune thrombocytopenia. Uncontrolled cellular immune response is one of the key triggers for the loss of immune tolerance in ITP patients. The purpose of this study was to investigate the association of IL-23/Th17, IL-17A and IL-17A rs2275913 gene polymorphism with ITP in Egyptian children.

Methods
60 patients with ITP and 50 healthy control children from Minia city- Egypt were involved. Serum levels of IL-23 and IL-17A were determined by enzyme-linked immunosorbent assay. The frequency of Th17 cells was measured using flow cytometer. Genotyping for IL-17A was performed via polymerase chain reaction-restriction fragment length polymorphism.

Results
Comparing children with ITP to controls, serum levels of IL-23 and IL-17A as well as Th17 cells percentage were significantly increased (p <  0.001). Also, higher levels of these ILs and Th17 cells percentage were associated with decreased platelet count within ITP patients (p <  0.001). Analysis of genotype frequencies for IL-17A rs2275913 polymorphism and its alleles (A, G) showed no significant difference between cases and controls. Likewise, no significant differences were demonstrated between acute and chronic ITP regarding both IL-17A rs2275913 polymorphism prevalence and levels of IL-23, IL-17A plus Th17 cells percentage. The frequency of A alleles was 85 and 86% within patients and controls, respectively.

Conclusions
Elevated levels of IL-23, IL-17A and Th17 cells may be involved in ITP pathogenesis while IL-17A polymorphism rs2275913 is not prevalent in Egyptian children with ITP.
Occurrence of tick-borne pathogens in questing Ixodes ricinus ticks from Wester Ross, Northwest Scotland
Authors: Olsthoorn Fanny , Sprong Hein , Fonville Manoj , Rocchi Mara , Medlock Jolyon , Gilbert Lucy , Ghazoul Jaboury 
Published: August 2021

Abstract
Background
Lyme borreliosis and other tick-borne diseases emerge from increased interactions between humans, other animals, and infected ticks. The risk of acquiring a tick-borne infection varies across space and time, so knowledge of the occurrence and prevalence of pathogens in ticks can facilitate disease diagnosis in a specific area and the implementation of mitigation measures and awareness campaigns. Here we identify the occurrence and prevalence of several pathogens in Ixodes ricinus ticks in Wester Ross, Northwest Scotland, a region of high tourism and tick exposure, yet data-poor in terms of tick-borne pathogens.

Methods
Questing I. ricinus nymphs (n = 2828) were collected from 26 sites in 2018 and 2019 and tested for the presence of tick-borne pathogens using PCR-based methods. Prevalence was compared with other regions of Scotland, England, Wales, and the Netherlands.

Results
Anaplasma phagocytophilum (4.7% prevalence), Borrelia burgdorferi sensu lato (s.l.) (2.2%), Babesia from clade X (0.2%), Rickettsia helvetica (0.04%), and Spiroplasma ixodetis (0.4%) were detected, but no Neoehrlichia mikurensis, Borrelia miyamotoi, or Babesia microti. Typing of A. phagocytophilum using a fragment of the GroEL gene identified the presence of both ecotype I and ecotype II. Genospecies identification of Borrelia burgdorferi s.l. revealed B. afzelii (53% of infected nymphs), B. garinii (9%), B. burgdorferi sensu stricto (7%), and B. valaisiana (31%). We found similar prevalence of A. phagocytophilum in Wester Ross as in the Netherlands, but higher than in other parts of Great Britain. We found lower B. burgdorferi s.l. prevalence than in England or the Netherlands, and similar to some other Scottish studies. We found higher prevalence of B. valaisiana and lower prevalence of B. garinii than in other Scottish studies. We found S. ixodetis at much lower prevalence than in the Netherlands, and R. helvetica at much lower prevalence than in England and the Netherlands.

Conclusions
As far as we know, this is the first description of S. ixodetis in Great Britain. The results are relevant for disease surveillance and management for public and veterinary health. The findings can also aid in designing targeted public health campaigns and in raising awareness among outdoor recreationists and professionals.

Graphical abstract
Long non-coding RNA CASC2 restrains high glucose-induced proliferation, inflammation and fibrosis in human glomerular mesangial cells through mediating miR-135a-5p/TIMP3 axis and JNK signaling
Authors: Zhu Dongju , Wu Xiang , Xue Qian 
Published: August 2021

Abstract
Background
Diabetic nephropathy (DN) is a common complication of diabetes. Long non-coding RNA (lncRNA) cancer susceptibility candidate 2 (CASC2) is reported to exert a protective role in DN by a previous study. The working mechanism underlying the protective role of CASC2 in DN progression was further explored in this study.

Methods
The expression of CASC2 and microRNA-135a-5p (miR-135a-5p) was determined by real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation ability was assessed by Cell Counting Kit-8 (CCK8) assay and 5-ethynyl-29-deoxyuridine (EDU) assay. Enzyme-linked immunosorbent assay (ELISA) was conducted to analyze the production of inflammatory cytokines in the supernatant. Western blot assay was performed to analyze protein expression. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to verify the target relationship between miR-135a-5p and CASC2 or tissue inhibitors of metalloproteinase 3 (TIMP3).

Results
High glucose (HG) treatment reduced the expression of CASC2 in human glomerular mesangial cells (HMCs) in a time-dependent manner. CASC2 overexpression suppressed HG-induced proliferation, inflammation and fibrosis in HMCs. miR-135a-5p was validated as a target of CASC2, and CASC2 restrained HG-induced influences in HMCs partly by down-regulating miR-135a-5p. miR-135a-5p bound to the 3ʹ untranslated region (3ʹUTR) of TIMP3, and CASC2 positively regulated TIMP3 expression by sponging miR-135a-5p in HMCs. miR-135a-5p silencing inhibited HG-induced effects in HMCs partly by up-regulating its target TIMP3. CASC2 overexpression suppressed HG-induced activation of Jun N-terminal Kinase (JNK) signaling partly through mediating miR-135a-5p/TIMP3 signaling.

Conclusions
In conclusion, CASC2 alleviated proliferation, inflammation and fibrosis in DN cell model by sponging miR-135a-5p to induce TIMP3 expression.
Labial gland-derived mesenchymal stem cells and their exosomes ameliorate murine Sjögren's syndrome by modulating the balance of Treg and Th17 cells
Authors: Li Boya , Xing Yixiao , Gan Yehua , He Jing , Hua Hong 
Published: August 2021

Abstract
Background
Sjögren's syndrome (SS) is a chronic, systemic autoimmune disorder characterized by sicca syndrome and/or systemic manifestations. The disease severely affects the health and life of patients, and the treatment of SS has always been a clinical challenge and essentially palliative. Mesenchymal stem cells (MSCs) have been reported to exert immunomodulatory effects and as a potential novel therapeutic strategy for SS. Labial gland-derived MSCs (LGMSCs) are a population of resident stem cells in the labial gland, first isolated by our group. Exosomes released by MSCs contain a large variety of bioactive molecules and considered to function as an extension of MSCs.

Methods
LGMSCs were isolated from patients who were needed surgery to remove the lip mucocele and LGMSCs derived exosomes (LGMSC-Exos) were isolated by ultracentrifugation. The non-obese diabetic (NOD) mice were treated with LGMSCs or LGMSC-Exos by tail vein injection. The saliva flow rate of mice was determined and salivary glands were dissected and stained with hematoxylin and eosin. In vitro, peripheral blood mononuclear cells (PBMCs) from SS patients were cocultured with LGMSCs or LGMSC-Exos. Percentage of T helper 17 (Th17) cells and regulatory T (Treg) cells were determined by flow cytometry. The serum levels of cytokines in NOD mice and in the supernatant of the co-culture system by ELISA.

Results
Treatment with LGMSCs or LGMSC-Exos reduced inflammatory infiltration in the salivary glands, and restored salivary gland secretory function in NOD mice. Importantly, LGMSCs or LGMSC-Exos were demonstrated to inhibit the differentiation of Th17 cells but promote the induction of Treg cells in NOD mice and PBMCs from SS patients in vitro, accompanied by reduced interleukin 17 (IL-17), interferon gamma, and IL-6 levels and enhanced transforming growth factor beta and IL-10 secretion by T cells.

Conclusions
LGMSCs are potential candidates for MSCs-based therapy and LGMSC-Exos might be utilized for establishing a new cell-free therapy against SS.
Antimicrobial stewardship, therapeutic drug monitoring and infection management in the ICU: results from the international A- TEAMICU survey
Authors: Lanckohr Christian , Boeing Christian , De Waele Jan J. , de Lange Dylan W. , Schouten Jeroen , Prins Menno , Nijsten Maarten , Povoa Pedro , Morris Andrew Conway , Bracht Hendrik 
Published: August 2021

Abstract
Background
Severe infections and multidrug-resistant pathogens are common in critically ill patients. Antimicrobial stewardship (AMS) and therapeutic drug monitoring (TDM) are contemporary tools to optimize the use of antimicrobials. The A-TEAMICU survey was initiated to gain contemporary insights into dissemination and structure of AMS programs and TDM practices in intensive care units.

Methods
This study involved online survey of members of ESICM and six national professional intensive care societies.

Results
Data of 812 respondents from mostly European high- and middle-income countries were available for analysis. 63% had AMS rounds available in their ICU, where 78% performed rounds weekly or more often. While 82% had local guidelines for treatment of infections, only 70% had cumulative antimicrobial susceptibility reports and 56% monitored the quantity of antimicrobials administered. A restriction of antimicrobials was reported by 62%. TDM of antimicrobial agents was used in 61% of ICUs, mostly glycopeptides (89%), aminoglycosides (77%), carbapenems (32%), penicillins (30%), azole antifungals (27%), cephalosporins (17%), and linezolid (16%). 76% of respondents used prolonged/continuous infusion of antimicrobials. The availability of an AMS had a significant association with the use of TDM.

Conclusions
Many respondents of the survey have AMS in their ICUs. TDM of antimicrobials and optimized administration of antibiotics are broadly used among respondents. The availability of antimicrobial susceptibility reports and a surveillance of antimicrobial use should be actively sought by intensivists where unavailable. Results of this survey may inform further research and educational activities.
RSST-ARGM: a data-driven approach to long-term sea surface temperature prediction
Authors: Zhu Linqian , Liu Qi , Liu Xiaodong , Zhang Yonghong 
Published: August 2021

AbstractFor the purpose of exploring the long-term variation of regional sea surface temperature (SST), this paper studies the historical SST in regional sea areas and the emission pattern of greenhouse gases, proposing a Grey model of regional SST atmospheric reflection which can be used to predict SST variation in a long time span. By studying the Grey systematic relationship between historical SST data, the model obtains the development law of temperature variation, and further introduces different greenhouse gas emission scenarios in the future as the indexes coefficient to determine the corresponding changing results of seawater temperature in the next 50 years. Taking the North Atlantic Ocean as an example, the cosine similarity test method is used to verify the model proposed in this paper. The accuracy of the model is as high as 0.99984. The model predicts that the regional SST could reach a maximum of $$15.3\,^{\circ }{\mathrm {C}}$$

15.3

∘

C

by 2070. This model is easy to calculate, with advantages of the high accuracy and good robustness.
Convergence and stability of an iteration process and solution of a fractional differential equation
Authors: Jubair Mohd , Ali Faeem , Ali Javid 
Published: August 2021

AbstractIn this paper, we prove that a three-step iteration process is stable for contractive-like mappings. It is also proved analytically and numerically that the considered process converges faster than some remarkable iterative processes for contractive-like mappings. Furthermore, some convergence results are proved for the mappings satisfying Suzuki’s condition (C) in uniformly convex Banach spaces. A couple of nontrivial numerical examples are presented to support the main results and the visualization is showed by Matlab. Finally, by utilizing our main result the solution of a nonlinear fractional differential equation is approximated.
Prevalence of extensively drug-resistant tuberculosis in a Chinese multidrug-resistant TB cohort after redefinition
Authors: Yao Cong , Guo Haiping , Li Qiang , Zhang Xuxia , Shang Yuanyuan , Li Tongxin , Wang Yufeng , Xue Zhongtan , Wang Lu , Li Liang , Pang Yu 
Published: August 2021

Abstract
Objectives
Recently, the definition of extensively drug-resistant TB (XDR-TB) has been revised. In this study, we conducted a descriptive and retrospective study to determine the prevalence of XDR-TB in a Chinese multidrug-resistant TB (MDR-TB) cohort.

Methods
Broth microdilution method was performed to determine in vitro susceptibilities of Mycobacterium tuberculosis (MTB) isolates to (FQs), bedaquiline (BDQ) and linezolid (LZD). The putative drug target genes conferring drug resistance were screened by DNA sequencing.

Results
A total of 425 MDR-TB isolates were included from 13 pilots in China. LZD and BDQ resistance were noted in 30 (7.1%) and 10 (2.4%) isolates. On the basis of latest definitions, 114 (26.8%) were MDR-TB, 282 (66.4%) were pre-XDR-TB, and 29 (6.8%) were XDR-TB. Among 311 FQ-resistant isolates, 265 harbored genetic mutations within QRDRs. The most common mutations were observed at codon 94 of gyrA, accounting for 47.2% of FQ-resistant MTB isolates. Only mutations within the Rv0678 gene were found to confer BDQ resistance in our cohort, conferring 40.0% of BDQ resistance. For LZD resistance, 53.3% of LZD-resistant isolates carried genetic mutations in rplC or 23S rRNA. The most frequent mutation was Cys154Arg in the rplC gene. In addition, we recorded two MDR-TB patients with resistance to both BDQ and LZD, of which one patient experienced continuous positive culture of MTB despite inclusion of efficacious moxifloxacin.

Conclusion
Our results demonstrate that the low prevalence of XDR-TB holds great promise for MDR-TB treatment with WHO-endorsed regimens containing BDQ-LZD combination, whereas the high prevalence of FQ-resistance in MDR-TB patients warrants national attention.
Neurofilament light and heterogeneity of disease progression in amyotrophic lateral sclerosis: development and validation of a prediction model to improve interventional trials
Authors: Witzel Simon , Frauhammer Felix , Steinacker Petra , Devos David , Pradat Pierre-François , Meininger Vincent , Halbgebauer Steffen , Oeckl Patrick , Schuster Joachim , Anders Simon , Dorst Johannes , Otto Markus , Ludolph Albert C. 
Published: August 2021

Abstract
Background
Interventional trials in amyotrophic lateral sclerosis (ALS) suffer from the heterogeneity of the disease as it considerably reduces statistical power. We asked if blood neurofilament light chains (NfL) could be used to anticipate disease progression and increase trial power.

Methods
In 125 patients with ALS from three independent prospective studies—one observational study and two interventional trials—we developed and externally validated a multivariate linear model for predicting disease progression, measured by the monthly decrease of the ALS Functional Rating Scale Revised (ALSFRS-R) score. We trained the prediction model in the observational study and tested the predictive value of the following parameters assessed at diagnosis: NfL levels, sex, age, site of onset, body mass index, disease duration, ALSFRS-R score, and monthly ALSFRS-R score decrease since disease onset. We then applied the resulting model in the other two study cohorts to assess the actual utility for interventional trials. We analyzed the impact on trial power in mixed-effects models and compared the performance of the NfL model with two currently used predictive approaches, which anticipate disease progression using the ALSFRS-R decrease during a three-month observational period (lead-in) or since disease onset (ΔFRS).

Results
Among the parameters provided, the NfL levels (P < 0.001) and the interaction with site of onset (P < 0.01) contributed significantly to the prediction, forming a robust NfL prediction model (R = 0.67). Model application in the trial cohorts confirmed its applicability and revealed superiority over lead-in and ΔFRS-based approaches. The NfL model improved statistical power by 61% and 22% (95% confidence intervals: 54%–66%, 7%–29%).

Conclusion
The use of the NfL-based prediction model to compensate for clinical heterogeneity in ALS could significantly increase the trial power.
NCT00868166, registered March
23, 2009; NCT02306590, registered December 2, 2014.
Extended high-frequency audiometry in healthy adults with different age groups
Authors: Wang Mingming , Ai Yu , Han Yuechen , Fan Zhaomin , Shi Peng , Wang Haibo 
Published: August 2021

Background It was well-documented that extended high-frequency (EHF, above 8 kHz) hearing test could be more sensitive comparing with the conventional measurement on frequency below 8 kHz, regarding the early prediction of auditory damage in certain population. However, hardly any age-specific thresholds of EHF in population with normal hearing ability were observed. This study aims to monitor the age-dependent hearing thresholds at EHF (from 9 to 20 kHz) in healthy hearing population. Methods A total of 162 healthy participants (from 21 to 70 years) with normal conventional pure tone audiograms were recruited and separated into five groups by age. Conventional pure tone average was performed with frequencies from 0.25 to 8 kHz under air conduction and from 0.25 to 4 kHz under bone conduction. EHF audiometry from 9 to 20 kHz was determined under air conduction. Results The effects of aging on hearing were evident at frequencies above 4 kHz. The hearing thresholds of EHF were less than 26 dB HL before 30 years-olds. Hearing abilities in EHF were deteriorated starting from the 31 ∼ 40 group and were most obvious in the 51 ∼ 60 group and the 61 ∼ 70 group with the maximum thresholds of 75 dB HL. Sensitivity of EHF was inversely proportional to the frequency within each age group, and to age among groups. Subjects under 30 years old were totally responsive up to 16 kHz, and 52.2% could respond to 20 kHz. Meanwhile, no responsiveness was recorded to 20 kHz in the 51 ∼ 60 group and even to 18 kHz in the 61 ∼ 70 group. No gender differences in hearing threshold was observed within each age group, except an obvious decline at frequencies of 4, 6, 8, and 9 kHz in male participants of the 41 ∼ 50 group. Conclusions Hearing thresholds at EHF from 9 to 20 kHz were more sensitive than at frequencies below 8 kHz for hearing measurement, and aging inversely affected hearing ability at EHF in healthy population. Hearing thresholds at EHF deteriorated with age and raising frequency, while the upper frequency limit decreased with aging. Graphical Abstract
Nephroprotective role of diosgenin in gentamicin-induced renal toxicity: biochemical, antioxidant, immunological and histopathological approach
Authors: Mishra Prachi , Mandlik Deepa , Arulmozhi S. , Mahadik Kakasaheb 
Published: August 2021

Abstract
Background
Aminoglycoside antibiotics, gentamicin (GM) owns the utmost nephrotoxic potential than other antibiotics from the same category. To the other side, diosgenin (DG) showed the antioxidant and anti-inflammatory property.

Results
The present study was aimed to explore the nephroprotective effect of diosgenin on gentamicin-induced renal toxicity in Wistar rats. Wistar albino rats were divided into six groups (n = 6): Normal control (NC), Nephrotoxicity control (GM), DG (20 mg/kg), DG (40 mg/kg), DG (80 mg/kg), accordingly. After the treatment, the nephroprotective effects of DG were assessed by measuring serum levels of creatinine (Cr), blood urea nitrogen (BUN), total proteins (TP), albumin and urea levels. Urine volume, proteins, electrolyte levels, creatinine clearance were also evaluated in urine samples. Oxidative stress was evaluated through the measurement of antioxidant stress markers in the kidney tissue. Changes in body weight and kidney weight were also recorded along with a histopathological examination of kidney sections. For evaluation of inflammation, TNF-α and IL-1β levels were measured in the blood serum using ELISA kits. GM intoxication induced elevated serum creatinine, BUN, urea, albumin and TP levels, urine electrolytes levels, pro-inflammatory cytokines, antioxidant parameters which were found to be decreased significantly in a dose-dependent manner in rat groups received DG which was also evidenced by the histological observations.

Conclusion
DG showed a significant nephroprotective effect in a dose-dependent manner by ameliorating the GM induced nephrotoxicity in Wistar rats.