bluuebunny/crossref_metadata_2025 huggingface dataset:
The efficacy of paxlovid in elderly patients infected with SARS-CoV-2 omicron variants: Results of a non-randomized clinical trial
Authors: Zhong Weijie , Jiang Xiufeng , Yang Xiaosheng , Feng Tiantong , Duan Zhixin , Wang Wei , Sun Zhaoliang , Chen Lingyan , Nie Xin , Zhu Chuanlong , Zhang Wenchuan , Li Yi
Published: September 2022

Objective

To evaluate the efficacy of Paxlovid in treating Chinese elder patients infected with SARS-CoV-2 omicron variants.

Materials and methods

We performed a non-randomized, controlled trial in Shanghai, China. Participants infected with SARS-CoV-2 omicron variants were enrolled. All patients were divided into the Paxlovid group or the control group according to the Chinese guideline (version 9). The nucleic acid shedding time was the primary endpoint.

Results

According to the inclusion criteria, 142 patients infected with omicron variants were enrolled, 36 patients who did not receive paxlovid were assigned to the control group, and 106 were in the Paxlovid group. The baseline characteristics were similar in either group. No significant difference in BMI, age, time from onset to patient enrollment, the severity on first admission, vaccination status, comorbidity, first symptoms, and laboratory results were recorded. Compared to the control group, participants in the Paxlovid group had a shorter viral shedding time [11.11 (2.67) vs. 9.32 (2.78), P = 0.001].

Conclusion

In Chinese elder patients infected with the variant of SARS-CoV-2 omicron, our data suggest that Paxlovid can significantly reduce the nucleic acid shedding time.
Distribution and genetic diversity of multi-drug-resistant Klebsiella pneumoniae at the human–animal–environment interface in Pakistan
Authors: Aslam Bilal , Chaudhry Tamoor Hamid , Arshad Muhammad Imran , Muzammil Saima , Siddique Abu Baker , Yasmeen Nafeesa , Khurshid Mohsin , Amir Afreenish , Salman Muhammad , Rasool Muhammad Hidayat , Xia Xueshan , Baloch Zulqarnain
Published: September 2022

Klebsiella pneumoniae is ubiquitous and known to be a notorious pathogen of humans, animals, and plant-based foods. K. pneumoniae is a recognized trafficker of antibiotic resistance genes (ARGs) between and from different ecological niches. A total of 775 samples (n = 775) were collected from September 2017 to August 2019 from humans, animals, and environmental sources by applying the random convenient sampling technique. A total of 120 (15.7%) samples were confirmed as K. pneumoniae. The distribution of K. pneumoniae among humans, the environment, and animals was 17.1, 12.38, and 10%, respectively. Isolates have shown significant resistance against all the subjected antibiotics agents except colistin. ARGs profiling revealed that the highest percentage prevalence (67.5%) of blaCTX–M was estimated in the isolates, and various carbapenem resistance genes that were found in the study were blaNDM–1 (43.3%), blaOXA–48 (38%), and (1.67%) blaKPC–2. Overall, 21 distinct sequence types (ST) and 13 clonal complexes (CCs) were found through the multi-locus sequence typing (MLST) analysis. Taking together, the distribution of multi-drug resistance (MDR) K. pneumoniae clones in the  community and associated environment is alarming for the health care system of the country. Health policymakers should consider the role of all the integral parts of humans, animals, and the associated environment intently to cope with this serious public and animal health concern.
Mechanisms of Zhenwu decoction for the treatment of renal fibrosis at various stages: What is the role of Corynebacterium?
Authors: Du Lijing , Zhang Yiping , Ji Shuai , Wang Leqi , Zhao Xiaoshan , Yan Shikai , Xiao Xue , Li Shasha
Published: September 2022

Many studies demonstrated that Zhenwu decoction (ZWD) is effective in the treatment of kidney fibrosis, whereas the mechanism remains unclear. In this work, a microbiomics-based strategy was used to investigate the mechanism of protective effects of ZWD on kidney fibrosis. Unilateral ureteral obstruction was used to replicate a rat model of renal fibrosis, and rats were divided into prophylactic, early, and progression stages according to the timing of administration. Feces was collected to perform microbiota evaluation by high-throughput 16S DNA sequencing. The results indicated that Corynebacterium, Alistipes, Dorea, and Lactonifactor were highlighted as key targeted flora of ZWD in the treatment of renal fibrosis, and their biological functions were related to inflammation, immunity, and renal excretion. Especially, Corynebacterium presented a significant positive correlation with the concentration of Cys-C, Scr, and BUN. The studies on the changes in inflammatory cytokines (INF-γ, IL-1β, IL-4, and TNF-α) and immunoglobulin (IgA, IgM, and IgG) confirmed the beneficial effects of ZWD on kidney fibrosis. Therefore, this study confirmed the protective effect of ZWD against renal fibrosis at various disease stages, and its mechanism was associated with re-establishing dysbiosis of the intestinal microbiota, reducing inflammation, as well as regulating immune functions. In particular, Corynebacterium may be a key flora in the treatment of renal fibrosis.
Bacterial and fungal communities within and among geographic samples of the hemp pest Psylliodes attenuata from China
Authors: Guo Litao , Tang Chao , Gao Chunsheng , Li Zhimin , Cheng Yi , Chen Jia , Wang Tuhong , Xu Jianping
Published: September 2022

The hemp flea beetle Psylliodes attenuata (Coleoptera: Chrysomelidae: Psylliodes) is a common pest of Cannabis sativa, including cultivars of both medicinal marijuana and industrial hemp. Both the larval and adult stages of this beetle can cause significant damages to C. sativa, resulting in substantial crop losses. At present, little is known about the bacterial and fungal community diversity among populations of this pest insect. In the present study, we obtained P. attenuata samples from nine field sites representing broad industrial hemp productions in China and analyzed their microbial communities using DNA metabarcoding. Bacterial sequences of all the samples were assigned to 3728 OTUs, which belonged to 45 phyla, 1058 genera and 1960 known species. The most common genera were Rickettsia, Wolbachia, and Candidatus_Brownia. Fungal sequences of all the samples were assigned to 910 OTUs, which belonged to 9 phyla, 308 genera and 464 known species. The most common fungal genera were Cladosporium, Cutaneotrichosporon, and Aspergillus. Principal coordinate analysis revealed a significant difference in the bacterial and fungal community structure among the nine P. attenuata populations. Understanding the microbial symbionts may provide clues to help develop potential biocontrol techniques against this pest.
RETRACTED: Young plasma reverses anesthesia and surgery-induced cognitive impairment in aged rats by modulating hippocampal synaptic plasticity
Authors: Li Yanan , Zhang Qi , Yan Wenyu , Wang Xupeng , Yu Jiaxu , Yin Chunping , Zhou Qi , Hou Zhiyong , Wang Qiujun
Published: September 2022

We investigated the protective effect of young plasma on anesthesia- and surgery-induced cognitive impairment and the potential underlying mechanism using bioinformatics, functional enrichment analysis, gene set enrichment analysis, Golgi-Cox staining, dendritic spine analysis, immunofluorescence assay, western blot analysis, and transmission electron microscopy. Furthermore, we performed behavioral assessments using the open field test, the novel object recognition test, and the Morris water maze test. We identified 1969 differentially expressed genes induced by young plasma treatment, including 800 upregulated genes and 1169 downregulated genes, highlighting several enriched biological processes (signal release from synapse, postsynaptic density and neuron to neuron synapse). Anesthesia- and surgery-induced cognitive impairment in aged rats was comparatively less severe following young plasma preinfusion. In addition, the decreased levels of synapse-related and tyrosine kinase B/extracellular signal-regulated protein kinase/cyclic adenosine monophosphate response element-binding protein (TrkB/ERK/CREB) signaling pathway-related proteins, dendritic and spine deficits, and ultrastructural changes were ameliorated in aged mice following young plasma preinfusion. Together, these findings suggest that young plasma reverses anesthesia- and surgery-induced cognitive impairment in aged rats and that the mechanism is associated with the activation of the TrkB/ERK/CREB signaling pathway and improvement in hippocampal synaptic plasticity.
Effect of traditional Chinese exercise combined with massage on pain and disability in patients with lumbar disc herniation: A multi-center, randomized, controlled, assessor-blinded clinical trial
Authors: Zhou Xin , Kong Lingjun , Ren Jun , Song Pengfei , Wu Zhiwei , He Tianxiang , Lv Zhizhen , Zhang Shuaipan , Sun Wuquan , Zhang Jiafu , Cai Junhao , Zhu Qingguang , Fang Min
Published: September 2022

Background

Herniation of the nucleus pulposus caused by disc degeneration and other reasons can cause low back pain and disability. In China, traditional Chinese exercises (TCEs) and traditional Chinese massage (TCM) are widely used to improve symptoms of pain and disability in patients with lumbar disc herniation (LDH). The safety and efficacy of combination therapy have not been studied.

Objectives

To assess the effect of traditional Chinese exercise combined with massage vs. traditional Chinese massage alone on pain, disability, lumbar mobility and gait performance in patients with LDH.

Methods

Multi-center, randomized clinical trial conducted at 4 hospitals in China and enrolling 272 patients with LDH. Participants were randomly assigned to TCEs plus TCM group or TCM alone group. The combined therapy group received 18 Tai Chi training sessions (30-min sessions 3 times a week) and regular TCM treatments over 6 weeks. The control group received TCM therapy alone and was instructed to maintain their usual daily physical activity. Outcome variables measured included Visual Analog Scale (VAS), Short Form of McGill Pain Questionnaire (SF-MPQ), Oswestry Disability Index (ODI), lumbar spine range of motion (ROM) and gait performance.

Results

Among the 272 randomized participants, 259 completed the study. The mean VAS score was 51.77 mm at baseline in the TCEs plus TCM group, and 50.93 mm for the TCM alone group. The reduction in the VAS score at week 6 was greater in the TC group than in the TCM group with a mean difference of 4.05 (95% CI, 2.15–5.95; P < 0.001), and the ODI score with between-group differences of 3.57 points (95% CI, 2.84–4.30 points; P < 0.001). Similar significantly different results were observed in SF-MPQ, walking speed, cadence, and lumbar ROM. No serious adverse events were reported throughout the study period.

Conclusion

Compared with TCM alone, TCEs combined with TCM treatment performed better in reducing pain and improving disability. The combination therapy could be considered a valuable treatment option for LDH patients, with potential therapeutic utility for middle-aged and elderly patients with LDH.
The patient journey with NMOSD: From initial diagnosis to chronic condition
Authors: Delgado-Garcia Guillermo , Lapidus Sheryl , Talero Rosa , Levy Michael
Published: September 2022

Objective

To better understand the patient experience with neuromyelitis optica spectrum disorder (NMOSD) through the course of the illness.

Background

NMOSD is a rare autoimmune disorder that causes recurrent inflammatory attacks of the optic nerve, spinal cord, and brain. Knowledge and awareness of NMOSD in the general medical community are often limited, resulting in potential delays in diagnosis and treatment.

Design/methods

We developed a comprehensive 101-question survey to understand the patient's perspective on their journey from initial presentation to present condition. The survey covered basic demographics, symptoms, medical tests used to reach a diagnosis, and the patient's psychosocial responses to their diagnosis. The survey included questions to determine internal consistency in responses. We shared the survey with members of the Neuromyelitis Optica (NMO) Clinic Facebook group and received responses from 151 patients. All data collected were self-reported and presented as summary statistics.

Results

The majority of survey responses were from patients who were female (83%) and White (76%), Asian (7%), or African American (7%). Initial symptoms of disease included fatigue, pain, stiffness/spasticity, bladder and bowel dysfunction, cognitive/emotional symptoms, and visual disturbances. Initial reactions to NMOSD diagnosis were frequently fear, anxiety, and/or depression. Mean (SD) time to diagnosis was 2.2 (3.2) years. First contact with a medical professional was felt to be not helpful or somewhat helpful for many patients (71%), in part due to uncertain diagnosis and/or treatment. However, once referred to specialists (primarily neurologists), the majority of patients (87%) reported finding a professional who could help. Tests leading to diagnosis included magnetic resonance imaging, lumbar puncture, and blood tests for autoantibodies including aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG). While approximately 30% of patients still felt challenged for a variety of reasons, most patients reported that having a diagnosis and being under the care of a specialist contributed to a comprehensive plan with hope for their future.

Conclusions

The NMOSD patient journey frequently begins with anxiety, fear, and frustration. Finding the right specialist and identifying appropriate screening tests can lead to earlier diagnosis and progression toward better patient outcomes.
Association between leukocyte subpopulations and hematoma expansion after spontaneous intracerebral hemorrhage: A retrospective cohort study
Authors: Qin Jiao , Wei Haihua , Liu Yuling , Du Lixin , Xia Jun
Published: September 2022

Aims

To verify the association between leukocyte subpopulations and hematoma expansion (HE) determined by two definitions in Chinese individuals who experienced spontaneous intracerebral hemorrhage.

Methods

We enrolled 471 patients. The 1/2ABC formula was used to gauge hematoma volume. The outcome was whether HE appeared within 72 h. We used Definition 1 (volume increase ≥6 mL or 33%) and Definition 2 (volume increase ≥12.5 mL or 33%) to define HE, respectively. Binary logistic regression analysis was used to assess the association between leukocyte subpopulations and HE. For statistically significant leukocyte subpopulations, we also performed subgroup analyses to assess differences between subgroups.

Results

Among 471 patients, 131 (27.81%) and 116 (24.63%) patients experienced HE based on Definition 1 and Definition 2, respectively. After adjusting for confounding factors, elevated monocyte count was associated with a higher risk of HE-Definition 1 [adjusted odds ratio (aOR) 2.45, 95% confidence interval (CI) 1.02–5.88, P = 0.0450] and HE-Definition 2 (aOR 2.54, 95% CI 1.04–6.20, P = 0.0399). Additionally, we compared the results before and after adjusting for coagulation parameters. Monocyte count was significantly correlated with HE only after adjusting for coagulation parameters. Increased neutrophil count was associated with a lower risk of HE-Definition 1 (aOR 0.91, 95% CI 0.84–1.00, P = 0.0463). No correlations were observed between lymphocyte and leukocyte counts and HE (P > 0.05), and no subgroup interactions were observed (interaction P > 0.05).

Conclusion

A higher monocyte count is associated with a higher HE risk regardless of the two definitions, after excluding the influence of the coagulation parameters, which facilitates risk stratification. Moreover, an increased neutrophil count is associated with a decreased risk of HE in the context of HE-Definition 1, which reflects the importance of standardizing the definition of HE.
Dyadic nonverbal synchrony during pre and post music therapy interventions and its relationship to self-reported therapy readiness
Authors: Yap Sun Sun , Ramseyer Fabian T. , Fachner Jörg , Maidhof Clemens , Tschacher Wolfgang , Tucek Gerhard
Published: September 2022

Nonverbal interpersonal synchronization has been established as an important factor in therapeutic relationships, and the differentiation of who leads the interaction appears to provide further important information. We investigated nonverbal synchrony – quantified as the coordination of body movement between patient and therapist. This was observed in music therapy dyads, while engaged in verbal interaction before and after a music intervention in the session. We further examined associations with patients’ self-reported therapy readiness at the beginning of the session. Eleven neurological in-patients participated in this study. Our results showed an increase in both nonverbal synchrony and patient leading after the music intervention. A significant negative correlation was found between self-reported therapy readiness and nonverbal synchrony after the music intervention. These findings point to the empathic ability of the music therapist to sense patients’ therapy readiness. Higher patient leading in nonverbal synchrony after the music intervention may thus indicate that the music intervention may have allowed dyadic entrainment to take place, potentially increasing self-regulation and thus empowering patients.
Personality and brain contribute to academic achievements of medical students
Authors: Xie Yingying , Yuan Congcong , Sun Mengru , Sun Jie , Zhang Ningnannan , Qin Wen , Liu Feng , Xue Hui , Ding Hao , Wang Sijia , He Jinyan , Hu Lizhi , Li Xiaoxia , Yu Chunshui
Published: September 2022

There are many factors that influence the academic achievements of medical students, but how personality and brain modulate the academic achievements of medical students remains unclear. The study collected the personality, brain imaging, and academic data from 448 medical students at Tianjin Medical University with admission time between 2008 and 2017. Four types of academic achievements, including behavioral and social sciences, clinical sciences and skills, basic biomedical sciences, and scientific methods, were assessed by the academic records of 58 courses. Personality was evaluated by Tridimensional Personality Questionnaire and Neuroticism Extraversion Openness Personality Inventory. Brain structural and functional properties, including gray matter volume, spontaneous brain activity and functional connectivity, were computed based on magnetic resonance imaging (MRI). Linear regression was used to evaluate the associations between personality and academic achievements. A voxel-wise correlation was used to identify areas of the brain where structural and functional properties were associated with academic achievements. Mediation analysis was used to test whether brain properties and personality independently contribute to academic achievements. Our results showed that novelty seeking (NS) was negatively correlated, and conscientiousness was positively correlated with all types of academic achievements. Brain functional properties showed negatively correlated with academic achievement in basic biomedical sciences. However, we did not find any mediation effect of the brain functional properties on the association between personality (NS and conscientiousness) and academic achievement in basic biomedical sciences, nor mediation effect of the personality (NS and conscientiousness) on the association between brain functional properties and academic achievement in basic biomedical sciences. These findings suggest that specific personality (NS and conscientiousness) and brain functional properties independently contribute to academic achievements in basic biomedical sciences, and that modulation of these properties may benefit academic achievements among medical students.
Aberrant resting-state connectivity of auditory, ventral attention/salience and default-mode networks in adults with attention deficit hyperactivity disorder
Authors: Blomberg Rina , Signoret Carine , Danielsson Henrik , Perini Irene , Rönnberg Jerker , Capusan Andrea Johansson
Published: September 2022

Background

Numerous resting-state studies on attention deficit hyperactivity disorder (ADHD) have reported aberrant functional connectivity (FC) between the default-mode network (DMN) and the ventral attention/salience network (VA/SN). This finding has commonly been interpreted as an index of poorer DMN regulation associated with symptoms of mind wandering in ADHD literature. However, a competing perspective suggests that dysfunctional organization of the DMN and VA/SN may additionally index increased sensitivity to the external environment. The goal of the current study was to test this latter perspective in relation to auditory distraction by investigating whether ADHD-adults exhibit aberrant FC between DMN, VA/SN, and auditory networks.

Methods

Twelve minutes of resting-state fMRI data was collected from two adult groups: ADHD (n = 17) and controls (n = 17); from which the FC between predefined regions comprising the DMN, VA/SN, and auditory networks were analyzed.

Results

A weaker anticorrelation between the VA/SN and DMN was observed in ADHD. DMN and VA/SN hubs also exhibited aberrant FC with the auditory network in ADHD. Additionally, participants who displayed a stronger anticorrelation between the VA/SN and auditory network at rest, also performed better on a cognitively demanding behavioral task that involved ignoring a distracting auditory stimulus.

Conclusion

Results are consistent with the hypothesis that auditory distraction in ADHD is linked to aberrant interactions between DMN, VA/SN, and auditory systems. Our findings support models that implicate dysfunctional organization of the DMN and VA/SN in the disorder and encourage more research into sensory interactions with these major networks.
Case report: Prompt response to radiotherapy and chemotherapy combined with crizotinib in gingival sarcomatoid squamous cell carcinoma with MET 14 mutation
Authors: Sun Zhenhua , Xia Bingjie , Zhang Ming , Xu Shuai , Ma Yingqian , Zhang Xianbo
Published: September 2022

Background

As a kind of squamous cell carcinoma of head and neck (HNSCC), gingival sarcomatoid squamous cell carcinoma (GSSCC) is a rare biphasic malignant neoplasm. To date, surgical resection was often utilized for gingival squamous cell carcinoma (GSCC), while for patients with advanced gingival carcinoma who cannot tolerate surgery, radiotherapy and chemotherapy can be regarded as a treatment strategy. Many molecular-targeted drugs were investigated and approved for the treatment of malignant diseases, including hematologic diseases and solid tumors. Although targeted therapies such as EGFR inhibitors have shown therapeutic efficacy in HNSCC, there are still some patients who cannot benefit from it. New therapeutic targets and strategies should be further explored.

Case presentation

An 83-year-old woman was referred to our hospital with left lower gingival mass for more than 1 month in June 2021. Pathologic diagnosis is sarcomatoid squamous cell carcinoma. Due to the large tumor at the time of diagnosis and poor quality of life, the patient was intolerant to surgery, so she was given radiotherapy (RT) combined with concurrent chemotherapy (CT) with albumin bound paclitaxel. According to next-generation sequencing (NGS) results (MET exon 14 skipping mutation-positive), she was treated with crizotinib, a tyrosine kinase inhibitor that targets MET. Through the comprehensive treatment, the patient’s condition promptly improved, clinical complete remission (CR) was achieved in 2 months, and 9-month progression-free survival (PFS) was obtained. She finally died from non-cancer-related diseases.

Conclusion

Here we report the treatment of a GSSCC patient with MET mutation, who responded to crizotinib promptly and positively. It provides a new reference for understanding MET abnormalities in GSSCC and offers a new idea for the targeted treatment of gingival carcinoma.
Development and validation of a 90-day mortality prediction model following endobiliary drainage in patients with unresectable malignant biliary obstruction
Authors: Termsinsuk Panotpol , Charatcharoenwitthaya Phunchai , Pausawasdi Nonthalee
Published: September 2022

Background

Palliative endobiliary drainage is the mainstay treatment for unresectable malignant biliary obstruction (MBO). Despite optimal drainage, the survival benefit is arguable. This study aimed to identify factors predicting post-endoscopic drainage mortality and develop and validate a mortality prediction model.

Methods

We retrospectively analyzed data for 451 patients with unresectable pancreatobiliary cancers undergoing first endoscopic retrograde cholangiopancreatography (ERCP)-guided endobiliary stent placement between 2007 and 2017. We randomly assigned patients in a 3:1 fashion into a derivation cohort (n=339) and validation cohort (n=112). Predictors for 90-day mortality post-stenting were identified from the derivation cohort. A prediction model was subsequently developed and verified with the validation cohort.

Results

The overall 90-day mortality rate of the derivation cohort was 46.9%, and the mean age was 64.2 years. The 2 most common diagnoses were cholangiocarcinoma (53.4%) and pancreatic cancer (35.4%). In all, 34.2% had liver metastasis. The median total bilirubin (TB) level was 19.2 mg/dL, and the mean serum albumin was 3.2 g/dL. A metallic stent was used for 64.6% of the patients, and the median stent patency time was 63 days. A total of 70.8% had TB improvement of more than 50% within 2 weeks after stenting, and 14.5% were eligible for chemotherapy. Intrahepatic obstruction (OR=5.69; P=0.023), stage IV cancer (OR=3.01; P=0.001), pre-endoscopic serum albumin (OR=0.48; P=0.001), TB improvement within 2 weeks after stenting (OR=0.57; P=0.036), and chemotherapy after ERCP (OR=0.11; P<0.001) were associated with 90-day mortality after stenting. The prediction model was developed to identify the risk of death within 90 days post-stent placement. The AUROC was 0.76 and 0.75 in derivation and validation cohorts. Patients with a score ≥ 1.40 had a high likelihood of death, whereas those scoring < -1.50 had a low likelihood of death. Additionally, a score ≥ 0.58 provided a 75.2% probability of death, which highlights the usability of the model.

Conclusions

This study proposes a useful validated prediction model to forecast the 90-day mortality of unresectable MBO patients after stenting. The model permits physicians to stratify the death risk and may be helpful to provide a proper palliative strategy.
Predictive value of baseline metabolic tumor volume for non-small-cell lung cancer patients treated with immune checkpoint inhibitors: A meta-analysis
Authors: Zhu Ke , Su Danqian , Wang Jianing , Cheng Zhouen , Chin Yiqiao , Chen Luyin , Chan Chingtin , Zhang Rongcai , Gao Tianyu , Ben Xiaosong , Jing Chunxia
Published: September 2022

Background

Immune checkpoint inhibitors (ICIs) have emerged as a promising treatment option for advanced non-small-cell lung cancer (NSCLC) patients, highlighting the need for biomarkers to identify responders and predict the outcome of ICIs. The purpose of this study was to evaluate the predictive value of baseline standardized uptake value (SUV), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) derived from 18F-FDG-PET/CT in advanced NSCLC patients receiving ICIs.

Methods

PubMed and Web of Science databases were searched from January 1st, 2011 to July 18th, 2022, utilizing the search terms “non-small-cell lung cancer”, “PET/CT”, “standardized uptake value”, “metabolic tumor volume”, “ total lesion glycolysis”, and “immune checkpoint inhibitors”. Studies that analyzed the association between PET/CT parameters and objective response, immune-related adverse events (irAEs) and prognosis of NSCLC patients treated with ICIs were included. We extracted the hazard ratio (HR) with a 95% confidence interval (CI) for progression-free survival (PFS) and overall survival (OS). We performed a meta-analysis of HR using Review Manager v.5.4.1.

Results

Sixteen studies were included for review and thirteen for meta-analysis covering 770 patients. As for objective response and irAEs after ICIs, more studies with consistent assessment methods are needed to determine their relationship with MTV. In the meta-analysis, low SUVmax corresponded to poor PFS with a pooled HR of 0.74 (95% CI, 0.57-0.96, P=0.02). And a high level of baseline MTV level was related to shorter PFS (HR=1.45, 95% CI, 1.11-1.89, P<0.01) and OS (HR, 2.72; 95% CI, 1.97-3.73, P<0.01) especially when the cut-off value was set between 50-100 cm3. SUVmean and TLG were not associated with the prognosis of NSCLC patients receiving ICIs.

Conclusions

High level of baseline MTV corresponded to shorter PFS and OS, especially when the cut-off value was set between 50-100 cm3. MTV is a potential predictive value for the outcome of ICIs in NSCLC patients.
Surgical approaches to intramedullary spinal cord astrocytomas in the age of genomics
Authors: Hersh Andrew M. , Jallo George I. , Shimony Nir
Published: September 2022

Intramedullary astrocytomas represent approximately 30%–40% of all intramedullary tumors and are the most common intramedullary tumor in children. Surgical resection is considered the mainstay of treatment in symptomatic patients with neurological deficits. Gross total resection (GTR) can be difficult to achieve as astrocytomas frequently present as diffuse lesions that infiltrate the cord. Therefore, GTR carries a substantial risk of new post-operative deficits. Consequently, subtotal resection and biopsy are often the only surgical options attempted. A midline or paramedian sulcal myelotomy is frequently used for surgical resection, although a dorsal root entry zone myelotomy can be used for lateral tumors. Intra-operative neuromonitoring using D-wave integrity, somatosensory, and motor evoked potentials is critical to facilitating a safe resection. Adjuvant radiation and chemotherapy, such as temozolomide, are often administered for high-grade recurrent or progressive lesions; however, consensus is lacking on their efficacy. Biopsied tumors can be analyzed for molecular markers that inform clinicians about the tumor’s prognosis and response to conventional as well as targeted therapeutic treatments. Stratification of intramedullary tumors is increasingly based on molecular features and mutational status. The landscape of genetic and epigenetic mutations in intramedullary astrocytomas is not equivalent to their intracranial counterparts, with important difference in frequency and type of mutations. Therefore, dedicated attention is needed to cohorts of patients with intramedullary tumors. Targeted therapeutic agents can be designed and administered to patients based on their mutational status, which may be used in coordination with traditional surgical resection to improve overall survival and functional status.
The accuracy of the axial length and axial length/corneal radius ratio for myopia assessment among Chinese children
Authors: Mu Jingfeng , Zeng Dan , Fan Jingjie , Liu Meizhou , Zhong Haoxi , Shuai Xinyi , Zhang Shaochong
Published: September 2022

Objectives

The aim of this study was to assess the association between axial length/corneal radius ratio (AL/CR ratio), AL, and refractive status and evaluate the accuracy of AL and AL/CR ratio for myopia assessment among Chinese children.

Methods

A diagnostic trial was conducted in Shenzhen Eye Hospital from June 2020 to December 2020. Cycloplegic refraction and demographic characteristic survey were carried out, and AL and CR were measured. The Pearson correlation analysis between AL, AL/CR ratio, and spherical equivalent (SE) was carried out. The sensitivity, specificity, Youden index, positive predictive value, and negative predictive value of the AL/CR ratio and AL for myopia assessment were analyzed using cycloplegic refraction as the gold standard by drawing receiver operating characteristic (ROC) curves.

Results

A total of 300 children aged 8–18 years participated in this study. The Pearson correlation coefficient between AL and SE was −0.667 (P < 0.05) and −0.754 (P < 0.05) between AL/CR ratio and SE. There were significant differences in SE, AL, and AL/CR ratio among different age groups (p < 0.05). SE decreased by 1.185 diopter (D) for every 1 mm increase in AL and decreased by 0.667 D for every 0.1 increase in the AL/CR ratio. Taking cycloplegic refraction SE ≤ −0.50 D as the gold standard for the diagnosis of myopia, the area under the ROC curve of AL for myopia assessment was 0.836 (95% confidence interval [CI]: 0.767–0.906), with specificity, sensitivity, and Youden index of 0.833, 0.767, and 0.600, respectively. The area under the ROC curve of AL/CR ratio for myopia assessment was 0.937 (95% CI: 0.878–0.996), with specificity, sensitivity, Youden index, positive predictive value, and negative predictive value of 0.703, 0.913, 0.622, 0.956, and 0.771, respectively. The area under the ROC curve of the combination of AL/CR ratio and parental myopia for myopia assessment was 0.976 (95% CI: 0.957–0.996).

Conclusion

The correlation between SE and AL/CR ratio was stronger than that between SE and AL in children. The AL/CR ratio may be an alternative indicator for myopia assessment in children, and the combination of demographic factors and AL/CR ratio can improve the accuracy of myopia assessment.
Long-term monitoring for short/branched-chain acyl-CoA dehydrogenase deficiency: A single-center 4-year experience and open issues
Authors: Rossi Alessandro , Turturo Mariagrazia , Albano Lucia , Fecarotta Simona , Barretta Ferdinando , Crisci Daniela , Gallo Giovanna , Perfetto Rosa , Uomo Fabiana , Vallone Fabiana , Villani Guglielmo , Strisciuglio Pietro , Parenti Giancarlo , Frisso Giulia , Ruoppolo Margherita
Published: September 2022

Introduction

Short/branched-chain acyl-CoA dehydrogenase deficiency (SBCADD) is an inherited disorder of L-isoleucine metabolism due to mutations in the ACADSB gene. The role of current diagnostic biomarkers [i.e., blood 2-methylbutyrylcarnitine (C5) and urine 2-methylbutyrylglycine (2MBG)] in patient monitoring and the effects of proposed treatments remain uncertain as follow-data are lacking. This study presents first systematic longitudinal biochemical assessment in SBCADD patients.

Methods

A retrospective, observational single-center study was conducted on newborns born between 2017 and 2020 and suspected with SBCADD. Biochemical, molecular, clinical and dietary data collected upon NBS recall and during the subsequent follow-up were recorded.

Results

All enrolled subjects (n = 10) received adequate protein intake and L-carnitine supplementation. Nine subjects were diagnosed with SBCADD. During the follow-up [median: 20.5 (4–40) months] no patient developed symptoms related to SBCADD. No patient normalized serum C5 and urine 2MBG values. In 7/9 SBCADD patients mean serum C5 values decreased or stabilized compared to their first serum C5 value. A major increase in serum C5 values was observed in two patients after L-carnitine discontinuation and during intercurrent illness, respectively. Urine 2MBG values showed moderate intra-patient variability.

Discussion

The relatively stable serum C5 values observed during L-carnitine supplementation together with C5 increase occurring upon L-carnitine discontinuation/intercurrent illness may support the value of serum C5 as a monitoring biomarker and the benefit of this treatment in SBCADD patients. The role of urine 2MBG in patient monitoring remains uncertain. As all patients were asymptomatic, no association between biochemical parameters and clinical phenotype could be investigated in this study.
ECMO in neonates: The association between cerebral hemodynamics with neurological function
Authors: Yu Shu-Han , Mao Dan-Hua , Ju Rong , Fu Yi-Yong , Zhang Li-Bing , Yue Guang
Published: September 2022

Extracorporeal membrane oxygenation (ECMO) is a superior life support technology, commonly employed in critical patients with severe respiratory or hemodynamic failure to provide effective respiratory and circulatory support, which is especially recommended for the treatment of critical neonates. However, the vascular management of neonates with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is still under controversy. Reconstruction or ligation for the right common carotid artery (RCCA) after ECMO is inconclusive. This review summarized the existed studies on hemodynamics and neurological function after vascular ligation or reconstruction hoping to provide better strategies for vessel management in newborns after ECMO. After reconstruction, the right cerebral blood flow can increase immediately, and the normal blood supply can be restored rapidly. But the reconstructed vessel may be occluded and stenotic in long-term follow-ups. Ligation may cause lateralization damage, but there could be no significant effect owing to the establishment of collateral circulation. The completion of the circle of Willis, the congenital anomalies of cerebral or cervical vasculature, the duration of ECMO, and the vascular condition at the site of arterial catheterization should be assessed carefully before making the decision. It is also necessary to follow up on the reconstructed vessel sustainability, and the association between cerebral hemodynamics and neurological function requires further large-scale multi-center studies.
Central nervous system involvement and thrombocytopenia as predictors of mortality in children with hemophagocytic lymphohistiocytosis
Authors: Harnchoowong Saralee , Soponkanaporn Sirisucha , Vilaiyuk Soamarat , Lerkvaleekul Butsabong , Pakakasama Samart
Published: September 2022

Introduction

Hemophagocytic lymphohistiocytosis (HLH) is a potentially life-threatening condition. This study aimed to evaluate treatment outcomes and identify prognostic-related factors in Thai children with HLH.

Materials and methods

We retrospectively reviewed the medical records of 76 pediatric patients with HLH who were treated at Ramathibodi Hospital between January 2004 and December 2019. Treatment outcomes were defined as early mortality (death within 30 days after diagnosis) and early treatment response (resolution of all clinical features and normalization of at least one HLH-related laboratory parameter within 4 weeks).

Results

The overall mortality rate was 38% (29/76), with an early mortality rate of 45% (13/29). Malignancy-associated HLH had the highest mortality rate (88%), followed by primary HLH (56%). The predictors of early mortality were central nervous system (CNS) involvement [OR 13 (95%CI 2–83), p = 0.007] and platelet counts <44 × 106/mm3 [OR 8 (95%CI 1.3–49), p = 0.024]. The predictors of early treatment response were no CNS involvement [OR 6.6 (95%CI 1.5–28.8), p = 0.011], platelet counts more than 44 × 106/mm3 [OR 8 (95%CI 2.1–30.9), p = 0.003], and total bilirubin levels <1.8 mg/dL [OR 4 (95%CI 1.1–14.8), p = 0.036]. In the mixed-model analysis, platelet counts in non-survivors increased significantly less than those in survivors, with a mean difference in platelet changes between the two groups of 94.6 × 106/mm3 (p = 0.003).

Conclusion

The independent predictors of early mortality in children with HLH were CNS involvement and low baseline platelet counts. A slow rate of platelet increases during the first week after diagnosis was also associated with mortality.
Prolonged antibiotic therapy increased necrotizing enterocolitis in very low birth weight infants without culture-proven sepsis
Authors: Zhu Keran , Gao Hui , Yuan Liping , Wang Lili , Deng Fang
Published: September 2022

Objectives

We aimed to identify the factors associated with necrotizing enterocolitis (NEC) and to assess the associations of the initial empirical antibiotic therapy (IEAT) duration and antibiotic therapy duration/hospital stay ratio (A/H ratio) before NEC with subsequent NEC in very low birth weight (VLBW) infants with gestational age less than 32 weeks without proven sepsis.

Methods

A retrospective study was conducted at the NICU of the First Affiliated Hospital of Medical University of Anhui province from June 2015 to May 2022, and 567 VLBW infants with gestational age less than 32 weeks were included in the study. We divided the VLBW infants into those with and without NEC according to modified Bell’s criteria. We then used descriptive statistics to identify the factors associated with NEC and multivariate analyses to evaluate the associations of IEAT duration and A/H ratio with the occurrence of NEC.

Results

Of the 567 VLBW neonates admitted to our center, 547 survived and reached the normal discharge criteria. Fifty-one infants (8.99%) were diagnosed as showing NEC. Infants with NEC had a longer total parenteral nutrition time, total enteral nutrition time, and IEAT duration, as well as a higher A/H ratio than those without NEC. In multivariate analyses adjusted for the other factors, IEAT duration was associated with an increased odds of NEC [odds ratio (OR) = 1.267; 95% confidence interval (CI), 1.128–1.423], and the A/H ratio was also associated with increased odds of NEC (OR = 8.718; 95% CI, 2.450–31.030). For the A/H ratio, the area under the curve (AUC) was 0.767 and the ideal cutoff was 0.357, and the sensitivity and specificity were 0.843 and 0.645, respectively.

Conclusion

Prolonged antibiotic therapy may increase the risk of NEC in VLBW infants with a gestational age of fewer than 32 weeks and should be used with caution.
EGCG protects the mouse brain against cerebral ischemia/reperfusion injury by suppressing autophagy via the AKT/AMPK/mTOR phosphorylation pathway
Authors: Wang Li , Dai Maosha , Ge Yangyang , Chen Jiayi , Wang Chenchen , Yao Chengye , Lin Yun
Published: September 2022

Stroke remains one of the leading reasons of mortality and physical disability worldwide. The treatment of cerebral ischemic stroke faces challenges, partly due to a lack of effective treatments. In this study, we demonstrated that autophagy was stimulated by transient middle cerebral artery occlusion/reperfusion (MCAO/R) and oxygen-glucose deprivation/reoxygenation (OGD/R). Treatment with (−)-epigallocatechin-3-gallate (EGCG), a bioactive ingredient in green tea, was able to mitigate cerebral ischemia/reperfusion injury (CIRI), given the evidence that EGCG administration could reduce the infarct volume and protect poststroke neuronal loss in MCAO/R mice in vivo and attenuate cell loss in OGD/R-challenged HT22 cells in vitro through suppressing autophagy activity. Mechanistically, EGCG inhibited autophagy via modulating the AKT/AMPK/mTOR phosphorylation pathway both in vivo and in vitro models of stroke, which was further confirmed by the results that the administration of GSK690693, an AKT/AMPK inhibitor, and rapamycin, an inhibitor of mTOR, reversed aforementioned changes in autophagy and AKT/AMPK/mTOR signaling pathway. Overall, the application of EGCG relieved CIRI by suppressing autophagy via the AKT/AMPK/mTOR phosphorylation pathway.
A novel 16-gene alternative mRNA splicing signature predicts tumor relapse and indicates immune activity in stage I–III hepatocellular carcinoma
Authors: Chen Xu-Xiao , Zhang Bao-Hua , Lu Yan-Cen , Li Zi-Qiang , Chen Cong-Yan , Yang Yu-Chen , Chen Yong-Jun , Ma Di
Published: September 2022

Background: Hepatocellular carcinoma (HCC) is a lethal disease with high relapse and dismal survival rates. Alternative splicing (AS) plays a crucial role in tumor progression. Herein, we aim to integratedly analyze the relapse-associated AS events and construct a signature predicting tumor relapse in stage I–III HCC.

Methods: AS events of stage I–III HCC with tumor relapse or long-term relapse-free survival were profiled to identify the relapse-associated AS events. A splicing network was set up to analyze the correlation between the relapse-associated AS events and splicing factors. Cox regression analysis and receiver operating characteristic curve were performed to develop and validate the relapse-predictive AS signature. Single-sample gene set enrichment analysis (ssGSEA) and the ESTIMATE algorithm were used to assess the immune infiltration status of the HCC microenvironment between different risk subgroups. Unsupervised cluster analysis was conducted to assess the relationship between molecular subtypes and local immune status and clinicopathological features.

Results: In total, 2441 ASs derived from 1634 mRNA were identified as relapse-associated AS events. By analyzing the proteins involved in the relapse-associated AS events, 1573 proteins with 11590 interactions were included in the protein–protein interaction (PPI) network. In total, 16 splicing factors and 61 relapse-associated AS events with 85 interactions were involved in the splicing network. The relevant genes involved in the PPI network and splicing network were also analyzed by Gene Ontology enrichment analysis. Finally, we established a robust 16-gene AS signature for predicting tumor relapse in stage I–III HCC with considerable AUC values in all of the training cohort, testing cohort, and entire cohort. The ssGSEA and ESTIMATE analyses showed that the AS signature was significantly associated with the immune status of the HCC microenvironment. Moreover, four molecular subgroups with distinguishing tumor relapse modes and local immune status were also revealed.

Conclusion: Our study built a novel 16-gene AS signature that robustly predicts tumor relapse and indicates immune activity in stage I–III HCC, which may facilitate the deep mining of the mechanisms associated with tumor relapse and tumor immunity and the development of novel individualized treatment targets for HCC.
Effectiveness and mechanism of metformin in animal models of pulmonary fibrosis: A preclinical systematic review and meta-analysis
Authors: Wu Xuanyu , Xiao Xiang , Chen Xinyu , Yang Maoyi , Hu Zhipeng , Shuai Sijia , Fu Qinwei , Yang Han , Du Quanyu
Published: September 2022

Background: Pulmonary fibrosis (PF) is a lung disease with no curative drug, characterized by a progressive decrease in lung function. Metformin (MET) is a hypoglycemic agent with the advantages of high safety and low cost and has been used in several in vivo trials to treat fibrotic diseases.

Objective: This study aimed to explore the efficacy and safety of MET in treating PF and elaborate on its mechanism.

Methods: Eight databases were searched for in vivo animal trials of MET for PF from the time of database creation until 1 March 2022. The risk of bias quality assessment of the included studies was conducted using SYRCLE’s risk of bias assessment. Pulmonary inflammation and fibrosis scores were the primary outcomes of this study. Hydroxyproline (HYP), type I collagen (collagen I), α-smooth muscle actin (α-SMA), transforming growth factor-β (TGF-β), Smad, AMP-activated protein kinase (AMPK), and extracellular signal–regulated kinase (ERK) protein expression in lung tissues and animal mortality were secondary outcomes. Effect magnitudes were combined and calculated using Revman 5.3 and Stata 16.0 to assess the efficacy and safety of MET in animal models of PF. Inter-study heterogeneity was examined using the I2 or Q test, and publication bias was assessed using funnel plots and Egger’s test.

Results: A total of 19 studies involving 368 animals were included, with a mean risk of bias of 5.9. The meta-analysis showed that MET significantly suppressed the level of inflammation and degree of PF in the lung tissue of the PF animal model. MET also reduced the content of HYP, collagen I, α-SMA, and TGF-β and phosphorylation levels of Smad2, Smad3, p-smad2/3/smad2/3, ERK1/2, and p-ERK1/2/ERK1/2 in lung tissues. MET also elevated AMPK/p-AMPK levels in lung tissues and significantly reduced animal mortality.

Conclusion: The results of this study suggest that MET has a protective effect on lung tissues in PF animal models and may be a potential therapeutic candidate for PF treatment.

Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=327285, identifier CRD42022327285.