bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fulfillment status of hypertriglyceridemia and hypofibrinogenemia in children with hemophagocytic lymphohistiocytosis and risks of multiple organ dysfunction syndrome and early mortality
Authors: Li Xun , Yan Haipeng , Luo Ting , Xiao Zhenghui , Gong Ling , Huang Jiaotian , Zhang Xinping , Zheng Mincui , Yao Zhenya , Zang Ping , Zhu Desheng , Lu Xiulan 
Published: April 2022

Abstract
Background
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder. How to stratify high risk patients is one of the current challenges for the treatment of HLH. HLH patients usually fulfill multiple but not all eight diagnostic criteria. Different combinations of the fulfilled criteria may naturally cluster into previously undescribed subsets or phenotypes that may have different pathophysiology and demonstrate different risks for a poor outcome. The objectives of this study were to identify HLH subgroups according to the fulfillment of diagnostic criteria and evaluate the risk of multiple organ dysfunction syndrome (MODS) and 30-day mortality for subgroups. We retrospectively collect medical records of patients with discharge diagnosis of HLH between June 2015 and October 2018 from a tertiary children’s hospital in China. Latent class analysis was used to identify class defining variables from HLH diagnostic items, and subgroups were defined according to different combinations of the class defining variables.

Results
Triglyceride and fibrinogen were identified as the class defining variables. When evaluated in combinations, patients with hypertriglyceridemia and normal fibrinogen levels during hospitalization had the lowest risks for MODS (27.8%, OR = 1) and 30-day mortality (18.8%, OR = 1), and patients with normal triglyceride and hypofibrinogenemia had the highest risks for MODS (86.2%, OR = 16.24, P = 0.0002) and 30-day mortality (57.1%, OR = 5.78, P = 0.0187). The fulfillment status of hypertriglyceridemia and hypofibrinogenemia within 72 h of hospital admission was also associated with the risk of adverse outcomes.

Conclusions
The fulfillment status of hypertriglyceridemia and hypofibrinogenemia were associated with the risks of MODS and 30-day mortality among pediatric HLH patients. Further studies are needed to validate this association and investigate its clinical utility in the severity evaluation for HLH.
Transmembrane protein 108 inhibits the proliferation and myelination of oligodendrocyte lineage cells in the corpus callosum
Authors: Wu Yongqiang , Zhong Yanzi , Liao Xufeng , Miao Xiangguang , Yu Jianbo , Lai Xinsheng , Zhang Yu , Ma Chaolin , Pan Haili , Wang Shunqi 
Published: April 2022

Abstract
Background
Abnormal white matter is a common neurobiological change in bipolar disorder, and dysregulation of myelination in oligodendrocytes (OLs) is the cause. Transmembrane protein 108 (Tmem108), as a susceptible gene of bipolar disorder, is expressed higher in OL lineage cells than any other lineage cells in the central nervous system. Moreover, Tmem108 mutant mice exhibit mania-like behaviors, belonging to one of the signs of bipolar disorder. However, it is unknown whether Tmem108 regulates the myelination of the OLs.

Results
Tmem108 expression in the corpus callosum decreased with the development, and OL progenitor cell proliferation and OL myelination were enhanced in the mutant mice. Moreover, the mutant mice exhibited mania-like behavior after acute restraint stress and were susceptible to drug-induced epilepsy.

Conclusions
Tmem108 inhibited OL progenitor cell proliferation and mitigated OL maturation in the corpus callosum, which may also provide a new role of Tmem108 involving bipolar disorder pathogenesis.
Identification of distinct slow mode of reversible adaptation of pancreatic ductal adenocarcinoma to the prolonged acidic pH microenvironment
Authors: Wu Tzu-Chin , Liao Chien-Yu , Lu Wei-Chien , Chang Chuang-Rung , Tsai Fang-Yu , Jiang Shih-Sheng , Chen Tsung-Hsien , Lin Kurt Ming-Chao , Chen Li-Tzong , Chang Wun-Shaing Wayne 
Published: April 2022

Abstract
Background
Pancreatic ductal adenocarcinoma (PDAC) is the most common pancreatic neoplasm with high metastatic potential and poor clinical outcome. Like other solid tumors, PDAC in the early stages is often asymptomatic, and grows very slowly under a distinct acidic pHe (extracellular pH) microenvironment. However, most previous studies have only reported the fate of cancerous cells upon cursory exposure to acidic pHe conditions. Little is known about how solid tumors—such as the lethal PDAC originating within the pancreatic duct-acinar system that secretes alkaline fluids—evolve to withstand and adapt to the prolonged acidotic microenvironmental stress.

Methods
Representative PDAC cells were exposed to various biologically relevant periods of extracellular acidity. The time effects of acidic pHe stress were determined with respect to tumor cell proliferation, phenotypic regulation, autophagic control, metabolic plasticity, mitochondrial network dynamics, and metastatic potentials.

Results
Unlike previous short-term analyses, we found that the acidosis-mediated autophagy occurred mainly as an early stress response but not for later adaptation to microenvironmental acidification. Rather, PDAC cells use a distinct and lengthy process of reversible adaptive plasticity centered on the early fast and later slow mitochondrial network dynamics and metabolic adjustment. This regulates their acute responses and chronic adaptations to the acidic pHe microenvironment. A more malignant state with increased migratory and invasive potentials in long-term acidosis-adapted PDAC cells was obtained with key regulatory molecules being closely related to overall patient survival. Finally, the identification of 34 acidic pHe-related genes could be potential targets for the development of diagnosis and treatment against PDAC.

Conclusions
Our study offers a novel mechanism of early rapid response and late reversible adaptation of PDAC cells to the stress of extracellular acidosis. The presence of this distinctive yet slow mode of machinery fills an important knowledge gap in how solid tumor cells sense, respond, reprogram, and ultimately adapt to the persistent microenvironmental acidification.
ICU bereaved surrogates’ comorbid psychological-distress states and their associations with prolonged grief disorder
Authors: Wen Fur-Hsing , Chou Wen-Chi , Huang Chung-Chi , Hu Tsung-Hui , Chiang Ming Chu , Chuang Li-Pang , Tang Siew Tzuh 
Published: April 2022

Abstract
Background/objective
Bereaved ICU family surrogates’ psychological distress, e.g., anxiety, depression, and post-traumatic stress disorder (PTSD), is usually examined independently, despite the well-recognized comorbidity of these symptoms. Furthermore, the few studies exploring impact of psychological distress on development of prolonged grief disorder (PGD) did not consider the dynamic impact of symptom evolution. We identified surrogates’ distinct patterns/states of comorbid psychological distress and their evolution over the first 3 months of bereavement and evaluated their associations with PGD at 6-month postloss.

Methods
A longitudinal observational study was conducted on 319 bereaved surrogates. Symptoms of anxiety, depression, PTSD, and PGD were measured by the anxiety and depression subscales of the Hospital Anxiety and Depression Scale, Impact of Event Scale-Revised scale, and the PGD-13, respectively. Distinct psychological-distress states and their evolution were examined by latent transition analysis. Association between psychological-distress states and PGD symptoms was examined by logistic regression.

Results
Three distinct comorbid psychological-distress states (prevalence) were initially identified: no distress (56.3%), severe-depressive/borderline-anxiety distress (30.5%), and severe-anxiety/depressive/PTSD distress (13.3%). Except for those in the stable no-distress state, surrogates tended to regress to states of less psychological distress at the subsequent assessment. The proportion of participants in each psychological-distress state changed to no distress (76.8%), severe-depressive/borderline-anxiety distress (18.6%), and severe-anxiety/depressive/PTSD distress (4.6%) at 3-month postloss. Surrogates in the severe-depressive/borderline-anxiety distress and severe-anxiety/depressive/PTSD-distress state at 3-month postloss were more likely to develop PGD at 6-month postloss (OR [95%] = 14.58 [1.48, 143.54] and 104.50 [10.45, 1044.66], respectively).

Conclusions
A minority of family surrogates of ICU decedents suffered comorbid severe-depressive/borderline-anxiety distress and severe-anxiety/depressive/PTSD symptoms during early bereavement, but they were more likely to progress into PGD at 6-month postloss.
Effects of orthoptic therapy in children with intermittent exotropia after surgery: study protocol for a randomized controlled trial
Authors: Xu Meiping , Zheng Fuhao , Peng Yiyi , Wang Chunxiao , Lou Jiangtao , Yu Huanyun , Wang Yuwen , Yu Xinping 
Published: April 2022

AbstractBackgroundIntermittent exotropia (IXT) is the most common type of exotropia in China. Surgery is usually required to align the eye deviation to maintain or obtain better binocular visual function. However, there is a high rate of exodrift or recurrence in surgically treated patients. Orthoptic therapy is sometimes recommended for IXT patients after surgery. However, there is a lack of high-quality randomized controlled trials to prove that orthoptic therapy could be an effective supplement to surgical treatment for IXT patients. The main purpose of this study is to test the clinical effectiveness of orthoptic therapy in long-term stabilization of postoperative IXT patient. This report describes the design and methodology of the Intermittent Exotropia Postoperative Treatment Clinical Trial, which is the first large-sample, blank-controlled, randomized clinical trial.MethodsA total of 136 IXT patients (aged 7 to 17 years) will be enrolled and assigned to the orthoptic therapy group or blank control group according to a simple randomization scheme. Patients in the orthoptic therapy group will receive at least 2 months of orthoptic therapy, such as anti-suppression, vergence, and accommodation training. Patients in the blank control group will receive only refractive correction. All enrolled patients will need regular follow-up observation until 24 months after surgery. The primary outcome will be the proportion of participants meeting suboptimal surgical outcomes in this 24-month follow-up, which is defined as (1) exodeviation of 10 prism diopters (PD) at distance or near using the simultaneous prism and cover test (SPCT) or (2) loss of 2 or more octaves of stereoacuity from baseline, at any masked follow-up visit examination. The secondary outcomes will be the exodeviation at distance and near using the simultaneous prism and alternate cover test (PACT), magnitude of fusional convergence, stereoacuity, and accommodation. Measurements will be taken at baseline and at the 6-, 12-, 18-, and 24-month follow-ups.DiscussionTo the best of our knowledge, this will be the first prospective, randomized controlled study of orthoptic training in IXT patients after surgery. The aim of this work is to confirm the efficacy of orthoptic therapy in reducing the proportion of recurrence among IXT patients after surgery and improving binocular vision function.Trial registrationChinese Clinical Trial RegistryChiCTR1900026891. Registered on 25 October 2019.
Aerobic exercise and telomere length in patients with systolic heart failure: protocol study for a randomized controlled trial
Authors: Franzoni Leandro T. , Garcia Eduardo L. , Motta Stephanie B. , Ahner Mabel M. , Bertoletti Otávio A. , Saffi Marco A. L. , da Silveira Anderson D. , Pereira Alexandre A. , Pereira Adamastor H. , Danzmann Luiz C. , Stein Ricardo 
Published: April 2022

Abstract
Background
Heart failure (HF) with reduced ejection fraction (HFrEF) is a syndrome that leads to fatigue and reduced functional capacity due to disease-related pathophysiological mechanisms. Aerobic exercise (AERO) plays a key role in improving HF outcomes, such as an increase in peak oxygen uptake (VO2peak). In addition, HF promotes cell senescence, which involves reducing telomere length. Several studies have shown that patients with a worse prognosis (i.e., reduced VO2 peak) also have shorter telomeres. However, the effects of AERO on telomere length in patients with HFrEF are still unknown. In an attempt to fill this gap, we designed a study to determine the effects of 16 weeks of aerobic training (32 sessions) on telomere length in HFrEF patients.

Methods
In this single-center randomized controlled trial, men and women between 50 and 80 years old will be allocated into two different groups: a moderate-intensity aerobic training and a control grouTelomere length, functional capacity, echocardiographic variables, endothelial function, and walking ability will be assessed before and after the 16-week intervention period.

Discussion
Understanding the role of physical exercise in biological aging in HFrEF patients is relevant. Due to cell senescence, these individuals have shown a shorter telomere length. AERO can delay biological aging according to a balance in oxidative stress through antioxidant action. Positive telomere length results are expected for the aerobic training group.

Trial registration
ClinicalTrials.gov NCT03856736. Registered on February 27, 2019
Invasive raccoon (Procyon lotor) and raccoon dog (Nyctereutes procyonoides) as potential reservoirs of tick-borne pathogens: data review from native and introduced areas
Authors: Myśliwy Izabella , Perec-Matysiak Agnieszka , Hildebrand Joanna 
Published: April 2022

AbstractIn recent decades, populations of the raccoon (Procyon lotor) and the raccoon dog (Nyctereutes procyonides) have increased and adapted to peri-urban and urban environments in many parts of the world. Their ability to rapidly colonize new territories, high plasticity and behavioral adaptation has enabled these two species to be considered two of the most successful invasive alien species. One of the major threats arising from continually growing and expanding populations is their relevant role in maintaining and transmitting various vector-borne pathogens among wildlife, domestic animals and humans. According to the WHO, over 17% of infectious diseases are vector-borne diseases, including those transmitted by ticks. Every year tick-borne pathogens (TBPs) create new public health challenges. Some of the emerging diseases, such as Lyme borreliosis, anaplasmosis, ehrlichiosis, babesiosis and rickettsiosis, have been described in recent years as posing important threats to global health. In this review we summarize current molecular and serological data on the occurrence, diversity and prevalence of some of the TBPs, namely Babesia, Theileria, Hepatozoon, Borrelia, Rickettsia, Bartonella, Anaplasma and Ehrlichia, that have been detected in raccoons and raccoon dogs that inhabit their native habitats and introduced areas. We draw attention to the limited data currently available on these invasive carnivores as potential reservoirs of TBPs in different parts of the world. Simultaneously we indicate the need for more research in order to better understand the epidemiology of these TBPs and to assess the future risk originating from wildlife.
Graphical Abstract
Sex-based differences in remote monitoring of biometric, psychometric and biomarker indices in stable ischemic heart disease
Authors: Barsky Lili , Speier William , Fuller Garth , Cheng Susan , Kim Andy , Joung Sandy , Arnold Corey , Dhawan Shivani , Lopez Mayra , Mastali Mitra , van den Broek Irene , Wei Janet , Spiegel Brennan , Van Eyk Jennifer E. , Bairey Merz C. Noel , Shufelt Chrisandra 
Published: April 2022

Abstract
Background
Sex-based differences are crucial to consider in the formulation of a personalized treatment plan. We evaluated sex-based differences in adherence and remotely monitored biometric, psychometric, and biomarker data among patients with stable ischemic heart disease (IHD).

Methods
The Prediction, Risk, and Evaluation of Major Adverse Cardiac Events (PRE–MACE) study evaluated patients with stable IHD over a 12-week period. We collected biometric and sleep data using remote patient monitoring via FitBit and psychometric data from Patient-Reported Outcomes Measurement Information System (PROMIS), Kansas City Cardiomyopathy (KCC) and Seattle Angina Questionnaire-7 (SAQ-7) questionnaires. Serum biomarker levels were collected at the baseline visit. We explored sex-based differences in demographics, adherence to study protocols, biometric data, sleep, psychometric data, and biomarker levels.

Results
There were 198 patients enrolled, with mean age 65.5 ± 11 years (± Standard deviation, SD), and 60% were females. Females were less adherent to weekly collection of PROMIS, KCC and SAQ-7 physical limitations questionnaires (all p < 0.05), compared to males. There was no difference in biometric physical activity. There was a statistically significant (p < 0.05) difference in sleep duration between sexes, with females sleeping 6 min longer. However, females reported higher PROMIS sleep disturbance scores (p < 0.001) and poorer psychometric scores overall (p < 0.05). A higher proportion of males had clinically significant elevations of median N-terminal pro-brain natriuretic peptide (p = 0.005) and high-sensitivity cardiac troponin levels (p < 0.001) compared to females.

Conclusions
Among females and males with stable IHD, there are sex-based differences in remote monitoring behavior and data. Females are less adherent to psychometric data collection and report poorer psychometric and sleep quality scores than males. Elevated levels of biomarkers for MACE are more common in males. These findings may improve sex-specific understanding of IHD using remote patient monitoring.
Bone marrow impairment during early [177Lu]PSMA-617 radioligand therapy: Haematotoxicity or tumour progression?
Authors: Kind Felix , Michalski Kerstin , Yousefzadeh-Nowshahr Elham , Meyer Philipp T. , Mix Michael , Ruf Juri 
Published: April 2022

Abstract
Background
The recent phase III VISION-trial confirms the treatment efficacy of radioligand therapy with [177Lu]PSMA-617 (PSMA-RLT) in metastatic castration-resistant prostate cancer (mCRPC). In PSMA-RLT, the relatively low absorbed bone marrow dose allows for multiple therapy cycles with relatively low risk of haematological adverse events (hAE). However, as disease progression itself may be a cause of bone marrow impairment, the aim of this study was to assess potential relations between impairment of haematological status and response to PSMA-RLT.

Methods
In this retrospective analysis, haematological parameters (HP) of 64 patients with mCRPC were systematically acquired over two cycles (12–16 weeks) of PSMA-RLT from baseline to restaging. Changes in HP were analysed qualitatively (CTCAE 5.0) and quantitatively. The HP changes from baseline were compared to quantitative and qualitative biochemical and imaging response, using PCWG3 and PROMISE criteria.

Results
All grade 3/4 hAE observed were associated with disseminated or diffuse bone involvement as well as biochemical non-response at restaging. Quantitatively, at baseline, HP inversely correlated with biochemical and volumetric (on PET) tumour burden as well as bone involvement pattern (p ≤ 0.043). Among patients with disseminated or diffuse bone involvement, percentage changes in HP (%HP) at restaging inversely correlated with serological and imaging tumour burden (p ≤ 0.017). Biochemical non-responders showed a significant decrease in %HP (p ≤ 0.001) while HP in biochemical responders remained stable (p ≥ 0.079).

Conclusion
During early cycles of PSMA-RLT, qualitative and quantitative bone marrow impairment appears to be closely associated with osseous tumour burden as only patients with advanced bone involvement and non-response to therapy exhibited high-grade haematological adverse events, showing a significant decline of haematological parameters. This implies that in patients with advanced mCRPC, non-response to PSMA-RLT may be a major cause of bone marrow impairment during early treatment cycles.
German Clinical Trial Register DRKS00013665. Registered 28 December 2017, retrospectively registered (www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00013665)
Basis for using thioredoxin as an electron donor by Schizosaccharomyces pombe Gpx1 and Tpx1
Authors: Ahmad Fawad , Latif Muhammad Faizan , Luo Ying , Huang Ying 
Published: April 2022

AbstractGlutathione (GSH) peroxidases (GPxs or GSHPx) and thioredoxin (Trx) peroxidases (TPxs) are two classes of peroxidases that catalyze the reduction of peroxides. GPxs and TPxs generally use GSH or Trx, respectively, to recycle the oxidized cysteine (Cys) residue in the protein. However, it is unclear why unlike human GPxs, the Schizosaccharomyces pombe Gpx1 (spGpx1) prefers Trx over GSH for recycling of the active-site peroxidatic Cys residue. Here, we compared spGpx1 and S. pombe Tpx1 (spTpx1) protein sequences with those of their respective homologs in Saccharomyces cerevisiae and humans. Our analysis revealed that like spTpx1, spGpx1 contains a pair of conserved Cys residues (Cys36 and Cys82). These two conserved Cys residues are named peroxidatic and resolving Cys residues, respectively, and are found only in GPxs and TPxs that prefer Trx as an electron donor. Our analysis suggested that Cys36 and Cys82 in spGpx1 are most likely to form a disulfide bond upon oxidation of Cys36. Molecular modelling predicted that a conformational change might be required for the formation of this disulfide bond. Evolutionary analysis suggested that fungal GPxs and TPxs are related by divergent evolution from a common ancestor. Our analyses support a prediction that while spGpx1 and spTpx1 are phylogenetically and functionally different, they evolved from a common ancestor and use a similar mechanism for recycling of the active-site peroxidatic Cys residue.