bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinguishing the lipid profile of GCK-MODY patients and its correlation with hsCRP levels
Authors: Ping Fan , Fu Junling , Xiao Xinhua 
Published: October 2022

AimsGlucokinase–maturity-onset diabetes of the young (GCK-MODY) is the most common monogenic diabetes in China. We have previously reported on the low levels of high-sensitivity C-reactive protein (hsCRP) in patients with GCK-MODY. In this study, we further explored the correlation between the serum lipid profiles and hsCRP levels of patients with different types of diabetes. We also proposed to determine the possible mechanism of macrovascular protection in GCK genetic variants.MethodsThe serum lipid profiles of the GCK-MODY group (n = 50) were compared with those of the hepatocyte nuclear factor-1 alpha (HNF1A)-MODY group (n = 19), the type 1 diabetes (T1D) group (n = 50), and the type 2 diabetes (T2D) group (n = 54). The associations between the lipid compositions and the hsCRP levels in each group were also explored.ResultsElevated levels of high-density lipoprotein cholesterol (HDL-C) were found in the GCK-MODY group (1.5 ± 0.27) compared with the T1D (1.2 ± 0.47, p &lt; 0.01) and T2D (1.3 ± 0.3, p &lt; 0.01) groups. On the other hand, a significantly lower LDL-C level (2.4 ± 0.69) in the GCK-MODY group compared with the T1D (2.7 ± 0.72, p &lt; 0.01) and T2D (2.9 ± 0.68, p &lt; 0.01) groups was also noted. A lower ratio of triglyceride to HDL-C (TG/HDL) and a lower hsCRP level were also found in the GCK-MODY group [TG/HDL = 0.38 (0.25–0.52), hsCRP = 0.2 mg/L (0.16–0.37)] compared with the T1D group [(TG/HDL = 0.56 (0.39–1.29), hsCRP = 0.56 mg/L (0.39–1.29), p &lt; 0.01] and the T2D group [(TG/HDL = 1.6 (1.1–2.68), hsCRP = 1.11 mg/L (0.66–2.34), p &lt; 0.01]. Although patients with HNF1A-MODY showed similar hsCRP levels [0.17 (0.08–0.52), p &gt; 0.05] compared with the patients in the GCK-MODY group, they had higher TG levels [1.01 (0.66–1.76), p &lt; 0.05] and TG/HDL ratios [0.84 (0.56–1.31), p &lt; 0.05]. Analysis of the correlations between the hsCRP levels and lipid profiles of each group confirmed that the LnhsCRP (natural logarithm-transformed hsCRP level) was positively correlated with the LnTG (natural logarithm-transformed TG) (r = 0.352, p = 0.011) and the Ln(TG/HDL) ratio (r = 0.283, p = 0.047) only in individuals with GCK-MODY.ConclusionsIndividuals harboring GCK variants have the characteristics of protective lipid profiles manifested as a higher level of HDL-C and a lower level of LDL-C compared with type 1 and 2 diabetes milletus (T1DM and T2DM, respectively) patients. In addition, lower ratios of TG/HDL were found to be associated with the inhibition of secretion of hsCRP, even when adjusted for the HbA1c levels in patients with GCK-MODY. It is suggested that the protective effect of macrovascular complications in GCK-MODY patients might partly be due to their unique lipid profiles associated with the suppression of inflammation.
Prognostic model for the exemption of adjuvant chemotherapy in stage IIIC endometrial cancer patients
Authors: Yang Xi-Lin , Yang Feng-Leng , Kou Ling-Na , Wu Da-Jun , Xie Cong 
Published: October 2022

BackgroundThis study aimed to develop a nomogram to predict the survival for stage IIIC endometrial cancer (EC) patients with adjuvant radiotherapy (ART) alone and personalize recommendations for the following adjuvant chemotherapy (ACT).MethodsIn total, 746 stage IIIC EC patients with ART alone were selected from the Surveillance, Epidemiology, and End Results (SEER) registry. Cox regression analysis was performed to identify independent risk factors. A nomogram was developed accordingly, and the area under the receiver operating characteristic curve (AUC) and C-index were implemented to assess the predictive power. The patients were divided into different risk strata based on the total points derived from the nomogram, and survival probability was compared between each risk stratus and another SEER-based cohort of stage IIIC EC patients receiving ART+ACT (cohort ART+ACT).ResultsFive independent predictors were included in the model, which had favorable discriminative power both in the training (C-index: 0.732; 95% CI: 0.704–0.760) and validation cohorts (C-index: 0.731; 95% CI: 0.709–0.753). The patients were divided into three risk strata (low risk &lt;135, 135 ≤ middle risk ≤205, and high risk &gt;205), where low-risk patients had survival advantages over patients from cohort ART+ACT (HR: 0.45, 95% CI: 0.33–0.61, P &lt; 0.001). However, the middle- and high-risk patients were inferior to patients from cohort ART+ACT in survival (P &lt; 0.001).ConclusionA nomogram was developed to exclusively predict the survival for stage IIIC EC patients with ART alone, based on which the low-risk patients might be perfect candidates to omit the following ACT. However, the middle- and high-risk patients would benefit from the following ACT.
Case Report: The novel hemizygous mutation in the SSR4 gene caused congenital disorder of glycosylation type iy: A case study and literature review
Authors: Wang Jun , Gou Xingqing , Wang Xiyi , Zhang Jing , Zhao Nan , Wang Xiaohong 
Published: October 2022

Background: Recently, the hemizygous variation of SSR4 gene has been reported to be associated with congenital disorder of glycosylation type Iy. To date, only 13 patients have been diagnosed with SSR4-CDG in the worldwide, but it has not been reported in the Chinese population.Methods: Whole-exome sequencing and gene copy number variation analysis were used to genetic analysis. The mRNA expression of SSR4 gene in blood was detected by Real-time Quantitative PCR. The clinical manifestations of all patients reported in the literature were reviewed.Results: WES analysis identified a de novo hemizygous variant c.269G&gt;A (p.Trp90*) of SSR4 gene in the proband with psychomotor retardation, microcephaly, abnormal facial features, and nystagmus. This variant has not been reported in previous studies. The in vivo mRNA expression of SSR4 gene in patient was significantly decreased. Literature review showed that all 14 patients, including our patient, presented with hypotonia, intellectual disability, developmental delay, microcephaly, and abnormal facial features, while most patients had feeding difficulties, growth retardation, and ocular abnormalities, and epilepsy and skeletal abnormalities are less common.Conclusion: We reported the first case of SSR4-CDG caused by SSR4 variant in Chinese population, expanded the clinical and mutation spectra of the disorder, clarified the genetic etiology of the patient, and offered support for the prenatal diagnosis of the index family.
Translation suppression underlies the restrained COVID-19 mRNA vaccine response in the high-risk immunocompromised group
Authors: Kim Kangsan , Narasimhan Madhusudhanan , Mahimainathan Lenin , Zhang Ray , Araj Ellen , Kim Elizabeth , Tharpe William , Greenberg Benjamin M. , Greenberg David E. , Li Quan-Zhen , Cheng Chi-An , Sarode Ravi , Malladi Srinivas , Muthukumar Alagarraju 
Published: October 2022

BackgroundImmunocompromised (IC) patients show diminished immune response to COVID-19 mRNA vaccines (Co-mV). To date, there is no ‘empirical’ evidence to link the perturbation of translation, a rate-limiting step for mRNA vaccine efficiency (VE), to the dampened response of Co-mV.Materials and methodsImpact of immunosuppressants (ISs), tacrolimus (T), mycophenolate (M), rapamycin/sirolimus (S), and their combinations on Pfizer Co-mV translation were determined by the Spike (Sp) protein expression following Co-mV transfection in HEK293 cells. In vivo impact of ISs on SARS-CoV-2 spike specific antigen (SpAg) and associated antibody levels (IgGSp) in serum were assessed in Balb/c mice after two doses (2D) of the Pfizer vaccine. Spike Ag and IgGSp levels were assessed in 259 IC patients and 50 healthy controls (HC) who received 2D of Pfizer or Moderna Co-mV as well as in 67 immunosuppressed solid organ transplant (SOT) patients and 843 non-transplanted (NT) subjects following three doses (3D) of Co-mV. Higher Co-mV concentrations and transient drug holidays were evaluated.ResultsWe observed significantly lower IgGSP response in IC patients (p&lt;0.0001) compared to their matched controls in 2D and 3D Co-mV groups. IC patients on M or S showed a profound dampening of IgGSP response relative to those that were not on these drugs. M and S, when used individually or in combination, significantly attenuated the Co-mV-induced Sp expression, whereas T did not exert significant influence. Sirolimus combo pretreatment in vivo significantly attenuated the Co-mV induced IgMSp and IgGSp production, which correlated with a decreasing trend in the early levels (after day 1) of Co-mV induced Sp immunogen levels. Neither higher Co-mV concentrations (6μg) nor withholding S for 1-day could overcome the inhibition of Sp protein levels. Interestingly, 3-days S holiday or using T alone rescued Sp levels in vitro.ConclusionsThis is the first study to demonstrate that ISs, sirolimus and mycophenolate inhibited Co-mV-induced Sp protein synthesis via translation repression. Selective use of tacrolimus or drug holiday of sirolimus can be a potential means to rescue translation-dependent Sp protein production. These findings lay a strong foundation for guiding future studies aimed at improving Co-mV responses in high-risk IC patients.
A systematic review and network meta-analysis of first-line immune checkpoint inhibitor combination therapies in patients with advanced non-squamous non-small cell lung cancer
Authors: Shao Taihang , Zhao Mingye , Liang Leyi , Tang Wenxi 
Published: October 2022

IntroductionClinical evidence suggests that first-line immune checkpoint inhibitor (ICI) combination therapies can improve survival in patients with advanced non-squamous non-small cell lung cancer (nsq-NSCLC). However, the optimal strategy remains unknown without a systematic comparison of their long-term effects.MethodsWe performed a systematic review and network meta-analysis by retrieving up-to-date literature from PubMed® (National Library of Medicine, Bethesda, MD, USA), Embase® (Elsevier, Amsterdam, Netherlands), MEDLINE® (National Library of Medicine), ClinicalTrials.gov (National Library of Medicine), and major international conference publications. Published studies and abstracts comparing first-line ICI combination therapies with other treatments for patients with advanced nsq-NSCLC were included. Restricted mean survival time (RMST) was measured over 12 months for progression-free survival (PFS) and 18 months for overall survival (OS), and the Royston–Parmar model was used to extrapolate and compare data for the long-term outcomes.ResultsWe included a total of 11 trials involving 12 therapies and 6,130 patients. Pembrolizumab plus chemotherapy exhibited the best overall survival (OS) benefit at both 18 and 60 months [RMST = 2.95, 95% confidence interval (CI) 1.96 to 3.97; life-years gained over a 5-year period = 2.18 years]. Nivolumab plus bevacizumab plus chemotherapy was found to present the best progression-free survival (PFS) benefit at 12 months (RMST 3.02, 95% CI 2.11 to 3.91), whereas atezolizumab plus bevacizumab plus chemotherapy showed the best PFS benefit at 36 months (life-years gained over 3 years = 1.22 years). Subgroup analyses showed that among patients with programmed death-ligand 1 (PD-L1) expression ≥ 50%, atezolizumab plus chemotherapy and nivolumab plus ipilimumab resulted in superior OS benefits at 18 and 60 months, respectively. Among patients with PD-L1 expression&lt; 1%, pembrolizumab plus chemotherapy was associated with OS benefits at both 18 and 60 months. Sintilimab plus chemotherapy was associated with relatively fewer grade ≥ 3 adverse events than other ICI combination therapies.ConclusionOur results show that ICI combination therapies showed better survival benefits than chemotherapy. Pembrolizumab plus chemotherapy could provide the best OS benefits to patients with advanced nsq-NSCLC, whereas atezolizumab plus bevacizumab plus chemotherapy could bring the best PFS benefits. The optimal ICI combination therapy varies depending on PD-L1 expression level.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=325005, identifier CRD42022325005.
Neuromuscular and acute symptoms responses to progressive elastic resistance exercise in patients with chronic obstructive pulmonary disease: Cross-sectional study
Authors: Calatayud Joaquin , Torres-Castro Rodrigo , Vera-Uribe Roberto , Olivares-Valenzuela Álvaro , Guzmán-González Benjamín , Torres María E. , Sepúlveda-Cáceres Nicolás , Andersen Lars L. , Cruz-Montecinos Carlos 
Published: October 2022

BackgroundQuadriceps muscle training is a key part in the rehabilitation of chronic obstructive pulmonary disease (COPD) patients. However, exercise intensity prescription and progression with the typically used elastic bands is challenging. We aimed to evaluate neuromuscular, acute symptoms and cardiorespiratory responses (heart rate and dyspnea) during progressive elastic resistance exercise in patients with COPD.MethodsFourteen patients diagnosed with moderate-very severe COPD performed knee extensions at different elastic resistance levels (i.e., colors). The neuromuscular activity was recorded using surface electromyography for the rectus femoris, vastus lateralis and vastus medialis, together with rate of perceived exertion, perceived quadriceps fatigue, dyspnea, oxygen saturation and heart rate.ResultsFor the vastus lateralis and rectus femoris, increase of muscle activity was evident from a two-level increment when using the red color. For the vastus medialis, there were no muscle activity progressions. Dyspnea, quadriceps fatigue and especially rate of perceived exertion increased in a dose-response fashion and were correlated with the resistance level and muscle activity at the three muscles.ConclusionHeavy elastic resistance exercise is feasible in COPD patients without excessive dyspnea and a stable cardiorespiratory response. In general, at least two elastic resistance increments are needed to enhance muscle activity for the vastus lateralis and rectus femoris, while there is no increase for the vastus medialis. These results may help to individualize exercise dosing during elastic resistance training in patients with COPD.
FeetBack–Redirecting touch sensation from a prosthetic hand to the human foot
Authors: Morand Rafael , Brusa Tobia , Schnüriger Nina , Catanzaro Sabrina , Berli Martin , Koch Volker M. 
Published: October 2022

IntroductionAdding sensory feedback to myoelectric prosthetic hands was shown to enhance the user experience in terms of controllability and device embodiment. Often this is realized non-invasively by adding devices, such as actuators or electrodes, within the prosthetic shaft to deliver the desired feedback. However, adding a feedback system in the socket adds more weight, steals valuable space, and may interfere with myoelectric signals. To circumvent said drawbacks we tested for the first time if force feedback from a prosthetic hand could be redirected to another similarly sensitive part of the body: the foot.MethodsWe developed a vibrotactile insole that vibrates depending on the sensed force on the prosthetic fingers. This self-controlled clinical pilot trial included four experienced users of myoelectric prostheses. The participants solved two types of tasks with the artificial hands: 1) sorting objects depending on their plasticity with the feedback insole but without audio-visual feedback, and 2) manipulating fragile, heavy, and delicate objects with and without the feedback insole. The sorting task was evaluated with Goodman-Kruskal's gamma for ranked correlation. The manipulation tasks were assessed by the success rate.ResultsThe results from the sorting task with vibrotactile feedback showed a substantial positive effect. The success rates for manipulation tasks with fragile and heavy objects were high under both conditions (feedback on or off, respectively). The manipulation task with delicate objects revealed inferior success with feedback in three of four participants.ConclusionWe introduced a novel approach to touch sensation in myoelectric prostheses. The results for the sorting task and the manipulation tasks diverged. This is likely linked to the availability of various feedback sources. Our results for redirected feedback to the feet fall in line with previous similar studies that applied feedback to the residual arm.Clinical trial registrationName: Sensor Glove and Non-Invasive Vibrotactile Feedback Insole to Improve Hand Prostheses Functions and Embodiment (FeetBack). Date of registration: 23 April 2019. Date the first participant was enrolled: 3 September 2021. ClinicalTrials.gov Identifier: NCT03924310.
Avatar and distance simulation as a learning tool – virtual simulation technology as a facilitator or barrier? A questionnaire-based study on behalf of Netzwerk Kindersimulation e.V.
Authors: Löllgen Ruth M. , Berger-Estilita Joana , Rössler Lisa A. , Mileder Lukas P. 
Published: October 2022

BackgroundVirtual simulation modalities have been implemented widely since the onset of the severe acute respiratory syndrome coronavirus 2 pandemic restrictions in March 2020, as educators face persistent restrictions to face-to-face education of medical students and healthcare professionals.There is paucity of published data regarding the benefits and barriers of distance and avatar simulation training modalities.MethodsFollowing a 2-day virtual pediatric simulation competition facilitated by Netzwerk Kindersimulation e.V., using remote human avatars and distance simulation, we conducted a multicenter survey to explore the advantages and challenges of avatar and distance simulation among participants. We used a modified Delphi approach to draft and develop the 32-item online questionnaire with 7-point Likert-like scales (7 being the highest rating).ResultsTwenty participants answered our questionnaire. Respondents indicated both a high overall satisfaction (median of 5.0 [Q25–Q75: 4.0–6.0] ) for avatar and distance simulation 6.0 (5.0–6.0), respectively, as well as a high achieved psychological safety with both simulation types (5.0 [4.0–6.0] vs. 5.0 [4.0–6.0]). The most frequently reported profits of avatar and distance simulation included the elimination of travel distances, associated lower costs, less time spent attending the education activity, and effective communication and leadership training, especially with avatar simulation. Most often named challenges were technical problems, limited reception of non-verbal cues and a spatial distance from the team/educator.DiscussionBased on the results of this pilot study, avatar and distance simulation can be employed successfully and appear to be good supplements to face-to-face simulation. Other studies are warranted to further explore the effectiveness of various types of virtual simulation compared to conventional presential simulation. We suggest using avatar-based simulation for targeted communication and leadership skills training and the application of distance simulation to bring simulation experts virtually to remote places where educator resources are lacking.
Effect of L. reuteri on bowel movements in children aged 6 months to 4 years: A double-blind randomized controlled trial
Authors: Jung Camille , Kalach Nicolas , Degas Vanessa , Jeridi Yasmine , Bertrand Valérie , Bellaiche Marc 
Published: October 2022

BackgroundChronic constipation is common in children and often requires prolonged laxative treatment. Preliminary studies suggest that the probiotic Limosilactobacillus reuteri (L. reuteri) may be useful in treating constipation in children, but these preliminary results need to be replicated. The objective of this study was to assess the efficacy of L. reuteri in infants and young children with chronic functional constipation.MethodsA prospective double-blind randomized placebo-controlled trial was conducted in 5 pediatric departments in France between June 2017 and June 2021. In all, 49 patients—ages 6 months to 4 years, and suffering from chronic constipation per Rome IV criteria—were randomly allocated to the test and control groups. For 4 weeks, all were orally administered 5 daily drops of the test (L. reuteri DSM 17938 at 108 colony-forming units per day) or control (placebo) treatment, respectively. Participants were clinically assessed at 4 and 8 weeks. Parents were asked to daily record the number of spontaneous bowel movements (SBMs), stool consistency, and the use of any additional laxatives. Informed consent was obtained from parents of all recruited patients, and the study was approved by both an ethics committee and the French National Agency for Medicines and Health Products Safety (ANSM). The study is registered on ClinicalTrials.gov (NCT03030664).ResultsThe change in SBMs relative to baseline was greater in the control group at week 4 (control: 0.27 ± 0.5; test: 0.23 ± 0.5; P = 0.01) and in the test group at week 8 (control: 0.26 ± 0.4; test: 0.22 ± 0.5; P = 0.03). At week 4, the groups did not differ in number of responders (≥3 stools per week, with no non-retentive fecal incontinence), use of rescue medication, scoring of pain during defecation (Faces Pain Scale–Revised), or stool consistency (Bristol Stool Form Scale).ConclusionThis double-blind randomized controlled trial did not confirm the efficacy of L. reuteri for treatment of chronic functional constipation in young children.
Characteristic time scale of cluster production at the Fermi energy
Authors: Pagano A. , Cardella G. , De Filippo E. , Geraci E. , Gnoffo B. , Lanzalone G. , Maiolino C. , Martorana N. S. , Pagano E. V. , Pirrone S. , Politi G. , Risitano F. , Rizzo F. , Russotto P. , Trifirò A. , Trimarchi M. 
Published: October 2022

The study of heavy-ion collisions in the Fermi energy domain (20 MeV/nucleon &lt; E/A &lt; 100 MeV/nucleon) is a fundamental research topic in modern nuclear physics. In the case of semi-peripheral collisions, the Fermi energy regime is characterized by the formation of a transient, neck-like structure that connects a projectile-like fragment (PLF) with a target-like fragment (TLF). The neck structure represents a precursor of the fireball which is a typical overlap of participating nucleons at relativistic energies (E/A&gt; 200 MeV/nucleon). It undergoes an expansion phase in a short time scale of the order of 100 fm/c with the formation of a low-density region of nuclear matter, therefore favoring the clusterization of intermediate mass fragments (IMFs) of atomic number Z (typically) less than 20. Particular emphasis is given to some relevant results obtained by the CHIMERA collaboration in the last decade, regarding the time scale of the production mechanisms of the intermediate mass fragments in neck fragmentation and their neutron enrichment.